Lose Weight By Controlling The Fat Storage Hormone

Trouble Spot Nutrition

Created by Janet Hradil, Trouble Spot Nutrition is a 3 Phase Hormonal Solution That Melts Away Trouble Spot Fat In Less Than 15 Minutes A Day. Leptin, cortisol, and testosterone all have an influence on our weight issues, but not many of us know it. Janet Hradil has created Trouble Spot Nutrition with the intent of teaching people how their hormones affect their weight loss efforts, and how nutrition can easily correct hormone issues and help fight fat faster than ever before. In each of your fat cells, there is an enzyme, 11 beta-hydroxysteroid dehydrogenase-1 (Hsd), that takes inactive cortisone (a hormone) and turns it into cortisol, a fat storing compound. If you have high amounts of Hsd, you will have high amounts of fat storage. While Hsd is genetically determined, you can use nutrition to reduce levels and stop the unwanted fat storage, even on your trouble spots. Continue reading...

Trouble Spot Nutrition Summary


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Leptin Stimulates Production of Anorexigenic Peptide Hormones

Arcuate Nucleus

The amount of leptin released by adipose tissue depends on both the number and the size of adipocytes. When weight loss decreases the mass of lipid tissue, lep-tin levels in the blood decrease, the production of NPY is diminished, and the processes in adipose tissue shown in Figure 23-32 are reversed. Uncoupling is diminished, FIGURE 23-33 Hormones that control eating. In the arcuate nucleus, two sets of neurosecretory cells receive hormonal input and relay neuronal signals to the cells of muscle, adipose tissue, and liver. Leptin and insulin are released from adipose tissue and pancreas, respectively, in proportion to the mass of body fat. The two hormones act on anorexigenic neurosecretory cells (red) to trigger release of a-MSH this produces neuronal signals to eat less and metabolize more fuel. Leptin and insulin also act on orexigenic neurosecretory cells (green) FIGURE 23-33 Hormones that control eating. In the arcuate nucleus, two sets of neurosecretory cells receive hormonal...

Cortisol Signals Stress Including Low Blood Glucose

A variety of stressors (anxiety, fear, pain, hemorrhage, infections, low blood glucose, starvation) stimulate release of the corticosteroid hormone cortisol from the adrenal cortex. Cortisol acts on muscle, liver, and adipose tissue to supply the organism with fuel to withstand the stress. Cortisol is a relatively slow-acting hormone that alters metabolism by changing the kinds and amounts of certain enzymes synthesized in its target cell, rather than by regulating the activity of existing enzyme molecules. In adipose tissue, cortisol leads to an increase in the release of fatty acids from stored TAGs. The fatty acids are exported to serve as fuel for other tissues, and the glycerol is used for gluconeogenesis in the liver. Cortisol stimulates the breakdown of muscle proteins and the export of amino acids to the liver, where they serve as precursors for gluconeogenesis. In the liver, cortisol promotes gluconeogenesis by stimulating synthesis of the key enzyme PEP carboxykinase (see...

Regulators of Lipolysis and Fat Storage

The processes of lipolysis and fat storage are regulated by hormonal factors, which either enhance or suppress the activities of HSL and LPL. Through the action of glucocorticoid receptors, glucocorticoids enhance LPL activity and promote abdominal deposition of fat. The density of glucocorticoid receptors is greater in the visceral abdominal depot than in the subcutaneous abdominal depot. Therefore, an increase in glucocorticoid secretion is associated with increases in abdominal fat deposition compared to other fat depots. Insulin favors fat storage by increasing LPL and decreasing HSL activity. Insulin has stronger antily-polytic effects in adipose located in the abdominal region compared to the femoral regions in both men and women. Paradoxically, insulin binding is stronger in the gluteal-femoral region than the abdominal region. Therefore, it has been hypothesized that insulin regulates lipolysis at the postreceptor level. Sex hormones, such as estrogen, testosterone, and...

Aldosterone and Cortisol Excess

In situations of aldosterone excess causing hypertension, there is usually an adrenal cortical adenoma (Conn's syndrome) or bilateral adrenal hyperplasia. Aldosterone promotes sodium retention and potassium excretion, leading to slight hypernatremia, extracellular volume (ECV) expansion, hypertension, and hypokalemic alkalosis. Unlike secondary causes of hyperaldosteronism, such as renal artery stenosis, in which aldosterone and renin levels are high, in primary hyperaldosteronism, renin is suppressed due to ECV expansion. In states of Cortisol excess, caused by either adrenal overproduction (Cushing's syndrome) or pituitary stimulation from an adrenocorticotrophin (ACTH) secreting adenoma (Cushing's disease), high Cortisol levels produce aldosterone-like mineralocorticoid effects. Two recently recognized causes of hypertension are apparent mineralocorticoid excess and glucocorticoid suppressible hyperaldosteronism. The first is due to failure to metabolize and inactivate Cortisol...

Leptin Triggers a Signaling Cascade That Regulates Gene Expression

The leptin signal is transduced by a mechanism also used by receptors for interferon and growth factors, the JAK-STAT system (Fig. 23-34 see Fig. 12-9). The lep-tin receptor, which has a single transmembrane segment, dimerizes when leptin binds to the extracellular domain of two monomers. Both monomers are phos-phorylated on a Tyr residue of the intracellular domain by a Janus kinase (JAK). The -Tyr residues become docking sites for three proteins that are signal transducers and activators of transcription (STATs 3, 5, and 6, sometimes called fat-STATS). The docked STATs are then phosphorylated on Tyr residues by the Leptin receptor monomer Leptin) J K) Leptin receptor monomer I Leptin J

The Leptin System May Have Evolved to Regulate the Starvation Response

Although much of the initial interest in leptin resulted from its possible role in preventing obesity, the leptin system probably evolved to adjust an animal's activity and metabolism during periods of fasting and starvation, not to restrict weight. The reduction in leptin level triggered by nutritional deficiency reverses the thermo-genic processes illustrated in Figure 23-32, allowing fuel conservation. Leptin activates AMP-dependent protein kinase (AMPK), which regulates many aspects of fuel metabolism. Leptin also triggers decreased production of thyroid hormone (slowing basal metabolism), decreased production of sex hormones (preventing reproduction), and increased production of glucocorti-coids (mobilizing the body's fuel-generating resources). By minimizing energy expenditures and maximizing the use of endogenous reserves of energy, these leptin-mediated responses may allow an animal to survive periods of severe nutritional deprivation.

Cortisol and CRH Expression

Cortisol is secreted under diverse conditions that impact both physiology and behavior. 3 Short-term cortisol release is protective and facilitates normal physiological and behavioral adaptive processes, whereas high levels of cortisol have detrimental effects on various regulatory processes such as immune and neuroendocrine systems. The behavioral and physiological effects of CRH and cortisol are often independent of one another however, cortisol can influence CRH neurons by inhibiting and affecting the responsiveness of CRH neurons. Cortisol can lead to increases in CRH production and expression in various regions of the brain. In fact, behavioral responses are influenced by cortisol, facilitating CRH expression.

Leptin ob Protein

For 40 years, scientists searched for a mechanism by which the brain could monitor body fat deposition in order to keep an animal's body weight constant. In 1994, a gene that controlled the expression of a protein produced by adipose tissue was identified. Circulating levels of this protein (the ob protein) could be measured in normal weight mice. However, in obese ob ob mice, which display marked overeating, this protein was absent due to a mutation of the ob gene. A series of studies demonstrated that the absence of this protein was responsible for over-consumption and obesity in the obese ob ob. As the ob protein reduces food intake and also increases metabolic energy expenditure, both of which would result in weight loss, it was named leptin from the Greek 'leptos' meaning thin. In general, circulating levels of leptin appear to reflect the current status of body fat deposition and increase with the level of adiposity demonstrating the responsiveness of endogenous leptin to weight...


The major glucocorticoid is cortisol, which is secreted in response to direct stimulation by adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. Secretion of ACTH is governed by the hormone corticotropin-releasing factor (CRF) from the hypothalamus. This normally occurs with a diurnal rhythm, with the highest levels in the morning and the lowest levels in the late evening. On stimulation by ACTH, the adrenal glands respond in minutes to secrete cortisol in direct proportion to the ACTH concentration. Cortisol is normally secreted at the rate of 20 to 25 mg day. Through negative feedback inhibition, the plasma cortisol level acts to suppress ACTH release. By an undefined mechanism, stress factors such as anoxia, trauma, infections, and hypoglycemia also can trigger CRF and ACTH release and produce cortisol levels several times normal. The release of CRF in response to stress is resistant to suppression through negative feedback inhibition. Cortisol is a potent hormone...

Pathophysiology of Uncontrolled Diabetes

Pathophysiology Loss Weight

The pathophysiologic events that affect blood glucose levels in states of mild-to-moderate insulin deficiency are classified into two broad categories. First, the normal pathways for glucose clearance after a meal are ineffective second, body fuel stores are broken down with release of other substrates that lead to inappropriate synthesis of more glucose. These events are brought about by insulinopenia and often are further promoted by the relative abundance of the counterregulatory hormones, glucagon, catecholamines, and, to a lesser extent, cortisol and growth hormone. In addition, hyperglycemia further inhibits pancreatic 0 cell insulin secretion, compounding the problem (''glucose toxicity'').

Decrease In Platelets Ptsd A 2 Receptors Ptsd

Alterations in urinary cortisol + a + Altered plasma cortisol with 24-hr sampling + (decrease) +(increase) aFindings of decreased urinary cortisol in older male combat veterans and holocaust survivors and increased cortisol in younger female abuse survivors may be explainable by differences in gender, age, trauma type, or developmental epoch at the time of the trauma. + indicates the availability of studies NT not tested. controls and patients with other psychiatric disorders. Relative elevations of the NE metabolite, MHPG, were found in their nighttime samples. No differences were found in baseline levels of plasma NE when compared with healthy subjects. This noradrenergic hyperreactivity in patients with PTSD may be associated with the conditioned or sensitized responses to specific traumatic stimuli. Women with PTSD secondary to childhood sexual abuse had significantly elevated levels of catecholamines (NE, E, and DA), cortisol and catecholamine metabolites, metane-phrine,...

Integration of Episodic and Tonic Signals within the CNS

Within these sites numerous neurochemicals (first neurotransmitters and then neuropeptides) have been identified as potent inhibitors and stimulators of feeding behavior. 5-HT has been implicated as a critical CNS satiety factor in the short-term regulation of food intake. Specifically, the 5-HT system appears to be sensitive to meal-generated satiety factors such as CCK, enterostatin, and ingested macronutrients. Moreover, 5-HT drugs appear to enhance satiety, suppress CNS NPY release, and inhibit hunger. 5-HT appears to mediate the effects of episodic meal-generated satiety on appetite. The second CNS system to be involved is that of the melanocortins, which appear integral in the action of circulating leptin on intake and (like 5-HT) its agonists also inhibit NPY functioning. Thus, the melanocortins may mediate the effects of tonic energy status on appetite. The melanocortins are one of the inhibitory systems through which the tonic adiposity...

Humor Elicitation Theory Of

One theory that integrates the diverse findings on hunger, eating, and weight, called the set-point theory (Keesey, 1980), suggests that a homeostatic mechanism that regulates food intake, fat reserves, and metabolism operates to keep an organism at its predetermined weight. According to set-point theory, which was first suggested by research with laboratory rats, no single area in the brain keeps track of weight. Rather, an interaction of metabolism, fat cells, and hormones keeps people at the weight for which their bodies are designed. A common, persistent psychological theory holds that being overweight is a sign of emotional disturbance, but research has failed to support this popular belief. However, tension and irritability can result from constant dieting (being hungry much of the time), and unhap-piness can result from being heavy in a society that discriminates against people who weigh more than the cultural ideal. Culture and ethnic background...

Dairy consumption energy intake and body weight

Over the long term, the hypothalamus regulates food intake in response to hormones that enter the brain from the peripheral circulation and whose plasma concentrations are related to adipose tissue mass (Schwartz et al., 2000). The two major hormones that have been implicated in the long-term regulation of food intake are leptin and insulin (Badman and Flier, 2005). However, it has recently been shown that ghrelin, a hormone secreted by specialized cells in the stomach, also meets the criteria for a long-term regulator of food intake (Cummings, 2006). Leptin is a hormone arising from adipose tissue and its plasma concentrations are directly proportional to the adipose tissue mass. Although insulin does not arise from adipose tissue, its concentration in blood at fasting and after food ingestion is influenced by adipose tissue mass. It has been proposed that both insulin (Biddinger and Kahn, 2006) and leptin (Munzberg and Myers, 2005) resistance in the brain lead to increased food...

Summary Episodic and Tonic Factors in the Regulation of Appetite

Mct1 Pathway

Endogenous 5-HT and leptin represent two aspects of negative feedback integral to the appetite control system (see Figure 3). Both systems appear to inhibit NPY functioning, the effect of leptin being partly mediated by melanocortins and other excitatory and inhibitory neuropeptides. 5-HT mediates the effect of meal-derived satiety factors derived from pre- and postingestive processes (such as CCK and enterostatin relsease) and promotes meal termination, prolonging the intermeal interval. By such a mechanism the body deals with the daily physiological fluxes that result from meal intake ensuring an approximately appropriate daily energy intake. Circulating leptin accurately reflects the current status of the body's energy store. Leptin levels continually modify total daily and meal food intake to maintain a sufficient but not excessive level of energy deposition. Thus, 5-HT and leptin represent two classes of signals short-term episodic and long-term tonic feedback, respectively. The...

Clinical Features

Significant clinical and laboratory differences exist between patients with primary and those with secondary adrenal insufficiency. With secondary adrenal failure, the capacity of the pituitary to secrete ACIH is impaired. Ihe level of aldosterone is largely unaffected because of its regulation by the renin-angiotensin system and the plasma potassium concentration. Ihe clinical manifestations of secondary adrenal failure are due to insufficiency of cortisol and adrenal androgens. In addition, insufficiency of other anterior pituitary hormones such as growth hormone, thyroid hormone, and gonadotropic hormone may cause clinical abnormalities.

Programming of the Adipoinsular Axis and Altered Adipogenesis

It is important to note that very few animal studies have addressed interactions between pre and postnatal nutrition. However, other studies that have investigated diet-induced obesity point to a link between peripheral leptin resistance and insulin resistance in the development of obesity. The physiological role of hyperleptinemia associated with caloric excess has been proposed to relate to the protection of nonadipocytes from lipid oversupply that would lead to steatosis and lipotoxicity.68 Elevated leptin production as a result of short-term caloric excess prevents the up-regulation of lipogenesis and increases fatty acid oxidation, thus reducing lipid supply to peripheral tissue during caloric excess.68 In diet-induced obesity, peripheral leptin function is at first normal. However, prolonged caloric excess results in dysregulation of post-receptor leptin signalling. This causes accumulation of triglycerides and lipid metabolites, providing fatty acid substrate for the damaging...

Homeorhetic Regulation of Metabolic Adaptations to Pregnancy

Currie 11 and, more recently, Bauman. 12 Examples of homeorhetic regulation in pregnant animals have been reviewed previously. 1,4 Several pregnancy-related hormones, including progesterone, estradiol, and placental lactogen (PL) have been suggested as homeorhetic modulators of observed changes in tissue responses to insulin and catecholamines, and associated metabolic adaptations to the state of pregnancy in ruminants. 1 A more recently suggested candidate is leptin, 4 adipose tissue expression and plasma concentration of which increase markedly in ewes during midpregnancy, independent of nutrition and energy balance. These hormones and their proposed actions are listed in Table 1. None of these putative regulators has been shown to have the integrative, pleiotropic influences that growth hormone (GH) has in lactating ruminants. 12,13 Possibly, the combined influence of these hormones is more significant than their varying individual influences at different stages of pregnancy....

The Lipostat Theory Predicts the Feedback Regulation of Adipose Tissue

The lipostat theory postulates a mechanism that inhibits eating behavior and increases energy consumption whenever body weight exceeds a certain value (the set point) the inhibition is relieved when body weight drops below the set point (Fig. 23-30). This theory predicts that a feedback signal originating in adipose tissue influences the brain centers that control eating behavior and activity (metabolic and motor). The first such factor, leptin, was discovered in 1994, and several others are now known. Leptin (Greek leptos, thin) is a small protein (167 amino acids) that is produced in adipocytes and moves through the blood to the brain, where it acts on receptors in the hypothalamus to curtail appetite. Leptin was first identified as the product of a gene designated OB (obese) in laboratory mice. Mice with two defective copies of this gene (ob ob genotype lowercase letters signify a mutant form of the gene) show the behavior and physiology of animals in a constant state of starvation...

The Interrelationship Between Psychopharmacology and Psychoneuroimmunology

One of the major pathways whereby the central nervous system regulates the immune system is via the hypothalamic-pituitary-adrenal (HPA) axis. Various neurotransmitters (e.g. serotonin, noradrenaline, acetylcholine) regulate the secretion of corticotrophin releasing factor (CRF) which controls the release of adrenocorticotrophic hormone (ACTH) from the anterior pituitary. ACTH directly activates the adrenal cortex to produce glucocorticoids (e.g. cortisol). Following the rise in the plasma concentration of the glucocorticoids, a negative feedback mechanism normally operates to block the further release of ACTH from the pituitary. In depression, however, there would appear to be an insensitivity of the central glucocorticoid receptors to this feedback regulation. As a consequence, the plasma concentration remains elevated and cannot be easily suppressed by a potent synthetic glucocorticoid such as dexamethasone. This forms the basis of the dexamethasone suppression test (DST) which is...

Summary and Conclusions

Mothers are growth retarded at birth and develop obesity, hypertension, hyperleptinemia, hyperinsulinemia and hyperphagia during postnatal life. Close associations between a major rise in circulating insulin and leptin concentrations and a large increase in appetite and fat mass provide evidence for disturbed endocrine communication between the hypothalamus, adipose tissue and the endocrine pancreas in the pathogenesis of programming-induced obesity. Hypercaloric nutrition during postnatal life greatly amplifies prenatal effects on metabolic abnormalities, obesity, overeating and diminished exercise behaviour. However, it remains to be determined whether postnatal obesity is a consequence of programming of sedentary behaviour or whether defects in appetite regulation and hyperphagia are the main underlying cause of the increased adiposity and the development of metabolic disorders. 18. Bispham J, Gopalakrishnan GS, Dandrea J et al. Maternal endocrine adaptation throughout pregnancy to...

Congenital adrenal hyperplasia

Congenital adrenal hyperplasia is the commonest form of virilisation and is due to a genetic enzyme defect which results in deficient secretion of cortisol. This results in reduced negative feedback to the pituitary resulting in a very high ACTH. This produces adrenal hyperplasia and excess androgen production, especially androsterone which is converted to testosterone peripherally. Androsterone is a 17-ketosteroid and testosterone is not. Therefore, virilisation with an elevated urinary 17-keto steroid level suggest adrenal origin, while a normal or only slightly elevated 17-ketosteroid suggests excess testosterone from ovary or testis. Congenital adrenal hyperplasia is treated by glucocorti-coids which supply cortisol requirements and suppress the ACTH. Cosmetic surgery may be required.

Initiation and Stimulation of Eating Mechanisms Underpinning Hunger

Neuropeptide Y (NPY) is probably the most studied appetite stimulatory peptide. NPY is found throughout the CNS and in particular abundance in the PVN of the hypothalamus. Hypothalamic NPY neurons that are implicated in appetite regulation project from the ARC to the PVN. Infusing NPY directly into the CNS or increasing release of NPY within the PVN promotes meal initiation and produces an immediate and marked increase in food intake, delaying the onset of satiety. The hyperpha-gic effects of NPY appear to be mediated by both NPY Y1 and Y5 receptors. Endogenous NPY is sensitive to a variety of peripherally generated signals. It is stimulated by the gut factor ghrelin, but inhibited by the pancreatic hormone amylin, the adiposity signal leptin, and the satiety neurotrans-mitter serotonin (5-HT). Like NPY, galanin-induced hyperphagia has been well documented. Early studies demonstrated that direct infusion of galanin into the hypothalamus of rodents stimulated feeding behavior....

Well Being Assessment Physiological Criteria

There is no single valid measure of stress (or well-being). Nevertheless, we can use physiological variables to assist in validation. The hormone most often used for measuring well-being is cortisol, the product of the mammalian adrenal cortex. One also can measure the levels of hormones and metabolites that are affected by cortisol. The sympathetic nervous system is the other major source of reactions to stress, pain, or fright. Stress to the animal leads to stimulation of those hypothalamic neurons that produce corticotropin releasing factor (CRF). 2 This is carried in the hypothalamic pituitary portal system to the anterior pituitary, where it stimulates release of adrenal corticotropic hormone (ACTH). This, in turn, stimulates release of the adrenal cortical hormones, in particular cortisol (in mammals) and corticosterone (in birds). The mineral corticoids aldo-sterone may also be released to a lesser degree. This hormonal cascade will take some time (minutes to hours), in...

Erythema multiforme and toxic epidermal necrolysis

This rare disease complex is discussed in depth elsewhere. Major systemic signs associated with excess adrenal Cortisol (and rarely progesterone) production include polyuria, polydypsia, an increase in appetite, muscle wasting, pot-bellied appearance and lethargy (Duesburg & Peterson, 1997 Helton-Rhodes, 1997 Boord & Griffin, 1999). Alopecia may be seen in up to 50 of cats with hyperadrenocorticism. An unusual cutaneous sign is fragile skin syndrome, in which the thin skin readily tears and leads to non-healing wounds that may be secondarily infected. The fragile skin syndrome is rare it may also be associated with excessive use of glucocorticoids and megestrol acetate, diabetes mellitus, hepatic lipidosis and cholangiocarcinoma, and is often idiopathic.

Physiology of Lactation

It is desirable that mammals eat adequate amounts of food in order to meet nutrient needs during all physiological states, and yet there are times, such as early lactation, when this does not occur. A number of authors have reviewed the literature to describe the metabolites, hormones, and neuropeptides involved in appetite regulation, 3-5 and continued progress in our knowledge of the regulation of appetite will likely advance both animal productivity as well as animal well being. If producers could stimulate food intake around the time of parturition, there should be a reduction in metabolic diseases, like ketosis or milk fever. Furthermore, managing animals to avoid excessive accumulation of body fat may preclude a host of problems that are common to overly conditioned animals as they undergo parturition. There appears to be consistent agreement that important appetite control centers of the hypothalamus include the arcuate nucleus and the lateral basal hypothalamus, although other...

Recognizing Causative Factors of Undernutrition

Age-related physiological reduction in appetite, 'anorexia of aging,' is well documented. Several factors have been implicated in the genesis of this phenomenon. Evidence suggests that the decrease in lean body mass, energy expenditure, and metabolic rate that occurs with advancing age may partially account for the reduction of food intake in healthy older persons. Age-related reduction in olfactory and gustatory receptor sensitivity may compromise the hedonic qualities of meals, further reducing the desire to eat. Similarly, age-related alterations in hormonal and neurotransmitter-mediated function may also play a role in suppressing food intake. Animal studies suggest that aging results in a reduction in the opioid feeding drive and an increase in the satiating effect of cholecystokinin. This may lead to the ingestion of smaller meals and prolonged periods of satiety between meals. More recently ghrelin, a hunger-inducing peptide hormone, has been shown to decrease with age....

Sanitation In Poultry Processing Plants

Ide can be used to saponify the fat and also to dipeptidize the protein deposits. Various alkaline phosphates and synthetic detergents are also used in meat processing plants. A new approach to cleaning involves the use of enzymes in a cleaning solution. A solution usually containing proteases (to break down protein deposits) is often used in a mild alkaline solution (to saponify the fat deposits). The main advantage of using enzymes is a significant reduction in corrosion in the plant. Because the alkalinity of the solution cannot be too high (otherwise will inactivate the enzymes), corrosion problems are minimized. However, it should be noted that enzyme solutions are more expensive to use, at least on a short-term basis.

Pathophysiology of Trauma and Hypovolaemia

A reduction in blood volume immediately activates low pressure receptors in the atria, walls of the ventricles, pulmonary arteries and great veins. High-pressure baroreceptors in the aortic arch and carotid body are stimulated by hypotension. Chemoreceptors in the carotid body are stimulated by severe hypotension (mean arterial pressure < 60 mmHg). Signals from these receptors are transmitted to the vasomotor centre in the medulla and pons. Autonomic afferents from the vasomotor centre lead to an increase in peripheral arteriolar and venous tone, and to an increase in heart rate and myocardial contractility. In severe hypotension large quantities of adrenaline are secreted by the adrenal medulla, and circulating noradrenaline is substantially increased by overspill from synaptic clefts. Adrenocorticotropic hormone (ACTH), growth hormone (GH), anti-diuretic hormone (ADH) and beta-endorphins are released from the pituitary in response to shock and plasma cortisol levels are also...

Adrenogenital Syndrome

The most common cause of adrenogenital syndrome in children is congenital adrenal hyperplasia secondary to deficiency of 21-hydroxylase. Defective steroidogenesis results in a deficiency of cortisol and an overproduction of intermediary metabolites. Affected infant boys appear normal, whereas infant girls have ambiguous genitalia. Adrenal insufficiency can also occur in patients who have been on long-term treatment with steroids. Initial resuscitation is with 0.9 NS until adequate perfusion is reestablished. Hypoglycemia is treated with intravenous glucose. In infants, 25 dextrose in a dose of 2 to 4 mL kg is usually adequate. In older children and adolescents, 50 dextrose in a dose of 1 to 2 mL kg is appropriate. Neonates are best treated with 10 dextrose at 1 to 2 mL kg, to avoid rapid shifts in osmolarity. Treatment also consists of initiating glucocorticoid therapy with cortisol at a dose of 50 mg m 2 dose intravenously every 6 h. Mineralocorticoid therapy is not necessary during...

Laparoscopic Adrenal Surgery

Laproscopy Surgery Adrenalectomy

The preoperative evaluation of a patient with an adrenal mass begins with a thorough history and physical exam focusing on the signs and symptoms of excess hormonal secretion (Table 12.1), as well as those resulting from a mass effect of the tumor consisting of abdominal, back, flank pain, and a palpable mass. Symptoms may be episodic, and therefore the history must be carefully elicited. All patients with known adrenal masses must undergo biochemical evaluation for hormonal function. Functional tumors may be clinically occult.2,3 For example, some pheochromocytomas remain clinically silent until surgical stress or manipulation during surgery, or some asymptomatic cortisol producing adenomas can suppress contralateral adrenal function resulting in Addisonian crises after surgical removal.3 An initial screening of serum electrolytes, urinary catecholamines, and serum and urinary basal cortisol is indicated in all patients,4 and additional testing should be pursued as indicated (Table...

CYP1A1 and Aryl Hydrocarbon Receptor AhR

The CYP1A1 p450 monooxygenase enzyme has recently been identified as a target of chemopreventative strategies. The protoxin dimethylbenz a anthracene (DMBA) is metabolized by CYP1A1 (and CYP1B1) into a DNA damaging agent that is a potent initiator of breast cancer (64). The CYP1A1 gene also catalyzes the conversion of estradiol to form hydroxylated estrogen high estrogen levels are associated with an increased risk of breast and ovarian cancers. The CYP1A1 enzyme is capable of metabolizing arachidonic acid into 19-OH-AA (major product) and 14,15-EET (minor product) (65), but no link between these metabolites and breast cancer initiation or progression has been uncovered. Additionally, CPY1A1 expression is upregulated by a wide array of environmental toxins such as dioxins (most notably TCDD) and polychlorinated biphenyls (PCBs). The CYP1A1 gene is induced by the AhR, which is translocated to the nucleus upon ligand binding to act as a transcription factor. Dioxins act as ligands of...

Two Arms Of The Immune System Affected By Stress

Glucocorticoids (GC) such as cortisol act by regulating expression of multiple GC-sensitive genes and thus the expression of proteins that determine the phenotype and function of cells responsible for coordinating the body's response to stress. Gene expression regulation results from the binding of GC to its receptor (GR), found primarily in the cytoplasm of target cells, with subsequent translocation of the hormone-activated GR into the nucleus. It is here that GR has its major effects on gene expression, by interacting either directly (GR-DNA binding, as shown in Fig. 3) or indirectly (GR-other protein-DNA binding not shown) with regulatory DNA in and around GC-sensitive genes. Glucocorticoids both induce and inhibit the expression of sensitive target genes, depending on the gene and the target cell affected. Thus, blood cortisol concentrations resulting from a stress response can have pronounced effects on immunity through altered expression of hundreds of immune cell genes....

Mammary Glands Hormonal Regulation

The mammary glands are fascinating organs that are designed to provide nutrients and immunological protection to the young. These glands are a microcosm of the organism in that they have a life cycle (Fig. 1), which proceeds with each subsequent pregnancy, parturition, and lactation. The first phase of the life cycle is mammogenesis or growth and development of the mammary gland. This includes the growth and proliferation of mammary epithelial cells that comprise ducts and alveoli myoepithelial cells required for milk ejection fat cells, fibroblasts, and extracellular matrix components the complex system of blood vessels found in the developed mammary gland, sensory, and motor fibers to innervate the glands and also cells of the lymphatic and immune systems to defend the mammary glands when necessary. At the end of pregnancy, the mammary glands prepare for birth of the young by undergoing biochemical differentiation and the onset of milk synthesis, also known as lacto-genesis (Fig....

Ontogeny Adipose Tissue

Adipose tissue, now considered an endocrine organ, secretes or expresses many potential endocrine factors, including leptin and insulin-like growth factor (IGF) system proteins. Therefore, the structrual and functional aspects of adipose tissue ontogeny are important to the growing and mature animal. Fat cell development commences by midgestation and is characterized by the appearance of a number of fat cell clusters, or primitive organs, which subsequently increase in number and size throughout fetal development (Table 1). 1-3 Primitive fat organs are vascular structures in presumptive adipose tissue with few or no fat cells (Fig. 1 Table 1). Fetal adipocyte development is spatially and temporally related to capillary development.1-2-1 Although angiogenesis appears to be linked to adipo-genesis, the major regulators of angiogenesis have not been examined in meat animal adipose tissue (Table 2). Brown adipose tissue (BAT) is responsible, in part, for nonshivering thermogenesis in the...

Biomedical Anthropology and the Evolution of Diabetes Thrifty Genotypes and Phenotypes

Most of the literature on genetic thriftiness has focused on selective pressures operating in adulthood. Kuzawa (1998) focuses on human infancy and early childhood. He reviewed the literature supporting a strong selective advantage of a quick insulin trigger with enhanced fat storage as a hedge against infant morbidity and mortality. Refeeding after starvation or respiratory and diarrheal illnesses is accompanied by increases in insulin production. Furthermore, infants who have suffered nutritional compromise in utero and are small for their gestational age gain weight with appropriate nutritional interventions but demonstrate reduced glucose tolerance and are at high risk for insulin resistance metabolic syndrome, or Syndrome X, later in life (Barker, 1994, 1999 Phipps et al., 1993 Raven, 1988). The Barker hypothesis of prenatal origins of later life diseases, including diabetes, compliments the thrifty gene hypothesis (Kuzawa, 1998).

Impact Of Catecholamines On Behavior

In the realm of stress, many different corporal systems interact to help the human organism respond. There is usually activation of the adrenergic neurons in the hypothalamus. There is a close link between the cortisol and adrenergic response. In fact, increases in norepinephrine induce cortisol-releasing hormone production. Stimulation of the adrenergic nervous system causes elevations in plasma epinephrine and norepinephrine levels. These produce an increase in glucose. Furthermore, epinephrine induces the breakdown of fats from adipose tissues. In these situations, epinephrine and norepinephrine promote increased heart rate and blood pressure. The purpose of these changes is to facilitate the delivery of needed material for fight or flight. Situations often perceived as stressful to the body include strenuous physical exertion, acute anxiety states, and serious cardiovascular compromise.

Action Potencial Note

Hypokalemia Heart Action Potential

As discussed in Chapter 40, the aldosterone receptors in CNT and principal cells can be activated by the glucocorticoid cortisol almost as well as by aldosterone. Because the plasma levels of cortisol are usually several-fold higher than those of aldosterone and exhibit large diurnal variations, the aldosterone signal would be drowned out if it were not for the presence of the enzyme 11 -hydroxysteroid dehydrogenase, which converts cortisol to cortisone, a steroid that does not bind to the mineralocorticoid receptor. Only the CNT and principal cells in the nephron express this enzyme, but it is found in other epithelia that are regulated by aldosterone (e.g., the colonic epithelium and sweat ducts), and it is responsible for the selective response of these cells to aldosterone and not to cortisol.

Peripheral Endocrine Organs

Adipocytes are targets of many hormones and secretors of the hormones leptin, resistin, and adipsin, as well as sites where energy is stored as fat. Leptin has satiety effects and has received much attention as a potential treatment for obesity. Blood concentrations of leptin correlate with fatness and may be means by which adipocytes communicate information about body condition to higher centers, suppressing appetite and stimulating reproductive processes. Exogenous leptin has positive actions on some reproductive processes.

Neurochemistry Of Aggression

Findings of studies of naturally behaving animal populations are consonant with the findings from experimentally induced aggression paradigms. Domesticated silver foxes, who easily tolerated human contact, had a higher level of midbrain and hypotha-lamic serotonin than wild silver foxes bred in captivity. The domesticated foxes also had a reduced density of 5-HT1A receptor binding in the hypothalamus. Rhesus monkeys with the highest blood levels of serotonin were socially dominant, whereas animals with decreased whole blood serotonin tended to be ostracized. Aggressive behavior was also associated with high levels of cortisol, suggesting greater stress. Adolescent male rhesus macaque monkeys show an inverse correlation between cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and risk taking and aggression in the wild. with personality disorders who exhibit impulsive and aggressive behavior have a blunted prolactin response to...

Biological and Behavioral Influences

The regulation of energy balance and appetite in particular has been the subject of a large amount of research. Much of this work has been carried out in relation to obesity and whether this can be linked to a faulty mechanism or genetic defect of some kind. This work is reviewed in detail elsewhere in this encyclopedia, but a number of different mechanisms have been proposed whereby energy intake and balance might be regulated. These include the adaptive thermogenesis theory (now largely discounted, this proposed that energy expenditure was flexible in some individuals and increased to expend excessive energy intakes) nutrient-based models of feeding in which the energy and or nutrient composition of the diet is considered to lead to appetite suppression via complex gut-fill cues (e.g., the effect of carbohydrates on neurotransmitters and the central nervous system) and the glucostat, lipostat, and leptin theories, which are considered to operate via satiety effects. However,...

Two Major Pathways Of The Stress Response

The degree to which homeostasis becomes unbalanced and leads to distress 1 is largely influenced by the impact of stress hormones on target cells. Glucocorticoids (primarily cortisol in farm animals) are the main effector endpoints of the neuroendocrine response to stressors, 2 and result from activation of the hypothalamus-pituitary-adrenal (HPA) axis (Fig. 1). Systemic cortisol concentrations increase several minutes after a perceived threat and can last for a number of hours and recur in waves if the threat (stressor) is not removed. The well-known antiinflammatory and immunosuppressive effects of cortisol may serve as physiological downregulators of initiated immune responses following infection or tissue damage. 3 However, contemporary management stressors that significantly and repeatedly activate the HPA axis in otherwise healthy animals cause pronounced changes in immune cell physiology, leading to disease susceptibility and clinical pathology.

Endocrine and other mediating mechanisms

Several factors influence the responses that are activated in response to exercise, including immunological experience and many biopsychosocial factors. Despite the diversity of these factors, a sterotypical set of neuroendocrine pathways are critically involved. The dramatic changes in fuel requirements, together with cardiovascular adjustments needed to accomplish the increased demand for muscle tissue oxygen supply, requires a strong regulation in order to maintain internal homeostasis during exercise. Changes in autonomic nervous activity and in hormone secretion are central in this respect. Muscular exercise is associated with an increase in the concentration of a number of stress hormones in the blood including epinephrine, norepinephrine, growth hormone, j3-endorphins and Cortisol the concentration of insulin slightly decreases with exercise. Studies where hormones were infused, hormone receptors were blocked by drugs, or the hormone production was inhibited by epidural...

Integrated Actions Of Metabolic Hormones

Metabolic fuels absorbed from the intestine are largely converted to storage forms in liver, adipocytes and muscle. It is fair to state that storage is virtually the exclusive province of insulin, which stimulates biochemical reactions that convert simple compounds to more complex storage forms and inhibits fuel mobilization. Hormones that mobilize fuel and defend the glucose concentration of the blood are called counter-regulatory and include glucagon, epinephrine, norepinephrine, cortisol, and GH. Secretion of most or all of these hormones is increased whenever there is increased demand for energy. These hormones act synergistically and together produce effects that are greater than the sum of their individual actions. In the example shown in Fig. 4, glucagon and epinephrine raised the blood glucose level primarily by increasing hepatic production. When cortisol was given simultaneously, these effects were magnified, even though cortisol had little effect when given alone....

Key Brain Structures Mediating Fear And Anxiety Behaviors

To underscore its survival importance, many brain areas with redundant circuits are involved to subserve this important constellation of behaviors. Critical brain structures capable of incorporating an individual's prior experience or memory into the appraisal of stimuli are amygdala, LC, hippocampus, thalamus, hypothalamus, periaqueductal grey (PAG), and pre-frontal cortex. Alterations in neurochemical and neurotransmitter systems that mediate the stress response also play a role in anxiety. Important neurotransmitters are corticotrophine-releasing factor (CRF), adrenocorticotrophic hormone (ACTH), norepinephrine (NE), epinephrine, dopamine, cortisol, benzodiazepines (Bzs), opioids, and other neurochem-ical systems.

Hypothalamic Control Of Feeding

Synaptic inputs to orexin hypocretin- and MSH-containing neurons in the LHA arise from many regions of the central neuraxis. Perhaps most relevant to the control of ingestive behavior and energy balance is a recently discovered circuit that originates in the arcuate nucleus of the hypothalamus. Early studies indicated that neurotoxic damage to the arcuate nucleus (e.g., as produced by systemic administration of monosodium glutamate during early development) could produce syndromes of overeating and obesity in laboratory animals. New and exciting research findings have provided a possible explanation for this phenomenon. In 1994, a hormone called leptin was discovered that appears to exert tremendously potent inhibitory effects on feeding behavior. Leptin also produces significant physiological effects on thermoregulation and on the reproductive, thyroid, and adrenal axes. Leptin is released continuously from adipocytes and is present at a relatively high concentration in plasma...

Cannabis and the cannabinoids

Tetrahydrocannabinol is metabolized in the liver to form active metabolites which are further metabolized to inactive polar compounds these are excreted in the urine. Some metabolites are excreted into the bile and then recycled via the enterohepatic circulation. Because of their high lipophilicity, most active metabolites are widely distributed in fat deposits and the brain, from which sources they are only slowly eliminated. The half-life of elimination for many of the active metabolites has been calculated to be approximately 30 hours. Accordingly, accumulation occurs with regular, chronic dosing. Traces of the cannabinoids can be detected in the blood and urine of users for many days after the last administration. There is some evidence of metabolic tolerance occurring after chronic use of the drug. THC and related cannabinoids readily penetrate the placental barrier and may possibly detrimentally affect foetal development.

Hormonal Response to Injury Infection and Cancer

Infection, cancer, or any injury to the body result in an increase in counterregulatory hormones as well as insulin concentration. As a result of cancer, sepsis, or injury, many patients develop the syndrome of insulin resistance even though they had no history of diabetes prior to cancer. In cancer patients, when the overall injury is smaller, many studies have failed to demonstrate an elevation in counterregula-tory hormones. Mild elevations in cortisol concentrations may contribute to the protein catabolism and increased gluconeogenesis. When serum insulin is measured with a sensitive assay, cancer patients demonstrate a small but significant elevation in serum insulin concentration. This is consistent with the observation that these patients have insulin resistance. Cancer patients, like diabetics, have a reduced glucose utilization and loss of the first-phase insulin The rise in serum cortisol as the host's response to the tumor is one of many factors that are responsible for the...

Body Weight and Energy Balance

Substitution of nonalcohol calories by alcohol calories, which are 'wasted' during metabolism Alcohol metabolism decreases lipid metabolism, promotes fat storage multicenter studies, alcoholic hepatitis patients demonstrate universal evidence for protein calorie malnutrition, according to the physical findings of muscle wasting and edema, low levels of serum albumin and other visceral proteins, and decreased cell-mediated immunity, whereas their 6-month mortality is related in part to the severity of malnutrition. Anorexia is a major cause of weight loss in alcoholic liver disease, and may be caused by increased circulating levels of leptin. Furthermore, active alcoholic hepatitis contributes to increased resting energy expenditure as another cause of weight loss. On the other hand, resting energy expenditure is normal in stable alcoholic cirrhotics who are also typically underweight or malnourished in part due to preferential metabolism of endogenous fat stores. At the same time, the...

Pharmacological Uses and Toxicity of Vitamin B6 Supplements

Impairment of glucose tolerance is common in pregnancy and may indeed be severe enough to be classified as gestational diabetes mellitus, which generally resolves at parturition, although in some subjects it may persist. High-estrogen oral contraceptives may also cause impaired glucose tolerance. This seems to be the result of increased tissue and blood concentrations of xanthurenic acid, because of the inhibition of kynureninase by estrogen metabolites. Xanthurenic acid forms a complex with insulin which has little or no hormonal activity. Vitamin B6 supplements may have a beneficial effect by activating apokynureninase or kynureni-nase that has been inactivated by undergoing transamination.

Hormonal Regulation of Fuel Metabolism

The minute-by-minute adjustments that keep the blood glucose level near 4.5 mM involve the combined actions of insulin, glucagon, epinephrine, and cortisol on metabolic processes in many body tissues, but especially in liver, muscle, and adipose tissue. Insulin signals these tissues that blood glucose is higher than necessary as a result, cells take up excess glucose from the blood and convert it to the storage compounds glycogen and tria-cylglycerol. Glucagon signals that blood glucose is too low, and tissues respond by producing glucose through glycogen breakdown and (in liver) gluconeogenesis and by oxidizing fats to reduce the use of glucose. Epi-nephrine is released into the blood to prepare the muscles, lungs, and heart for a burst of activity. Cortisol mediates the body's response to longer-term stresses. We discuss these hormonal regulations in the context of three normal metabolic states well-fed, fasted, and starving and look at the metabolic consequences of diabetes...

Hepatic Glucose Metabolism

Gluconeogenesis is elevated in head and neck cancer patients and also in lung cancer patients. Gluconeogen-esis accounts for approximately 50 of the overall glucose production after an overnight fast. It was demonstrated that glucose carbon recycling was elevated in five of seven published studies. Glucose carbon recycling is an indicator of increased gluconeogenesis. The ability to measure gluconeogenesis was not possible in humans until recently, when a method using U-13C glucose and isotopomer analysis was developed. The Cori cycle is increased in cancer patients and has been estimated to account for 300 kcal of energy loss per day. In 70 of published studies, cancer patients have a significant elevation in the rate of gluconeogenesis compared to normal weight-matched controls. Gluconeo-genesis was directly related to the morning blood cortisol concentration in both the normal volunteers (r 0.913, p < 0.01) and the cancer patients (r 0.595, p < 0.05). In the septic host, the...

The Acute Phase Response and Alzheimer Disease

For example, administration of Cortisol reduces hippocampal glucose metabolism in the normal elderly but not in AD (75). Peripheral markers of the APR may be induced in AD by excessive cytokine production in the CNS (particularly of IL-1), and possibly also by cytokine production by other tissues such as the thyroid (119) when AD is caused by genetic factors. Elevated plasma levels of cortisol have been found in moderate to severe AD (65,75,132,234,283,313). Orell and O'Dwyer (283) have explained that this may be initiated by excessive cytokine production by injured brain cells which trigger release of corticotropin releasing factor (CRF) from the hypothalamus. CRF stimulates corticotropin release from the pituitary which in turn stimulates glucocorticoid release from the adrenal glands. The activity of this loop is, in part, regulated by the binding of glucocorticosteroid to corti-costeroid receptors in the hippocampus. In animals, aging is...

Gender Differences In Pd And Clinical Endpoints

One study cited earlier showed that the oral clearance and the apparent volume of distribution of prednisolone were both higher in men than women, but these PK differences were not accompanied by PD differences (106). Specifically, the 50 inhibitory concentration (IC50) values for effects of prednisolone on cortisol secretion and T-helper lymphocyte or neutrophil trafficking were not statistically different between men and women. However, another group found a significantly smaller IC50 value in women (0.1 vs. 1.7 ng mL) for methylpredni-solone suppression of cortisol secretion, indicating increased sensitivity (131). Gender-based differences in the pharmacodynamics of prednisolone may be mediated by endogenous estrogens for instance, the IC50 values for effects of methylprednisolone on basophil trafficking are related to estradiol concentrations in a log-linear fashion in women, with increased sensitivity found at higher estra-diol concentrations (131). An interesting example of...

Meat Quality in Cattle Live Evaluation

Trained live cattle evaluators look at many specific places on an animal's body to help correctly estimate quality grade. One of the most important places to evaluate is tail pones (fat deposits that accumulate around the tail-head of an animal) (Fig. 1B). 1 The larger the tail pones, the higher the cattle graded for English, Dairy, and Exotic cattle. 2 Lower quarter (Fig. 1E) refers to the fat deposits along the inner thighs of the animal. Lower quarter has a positive relationship with quality grade. 2 This trait is most effective when predicting quality grade of English cattle and is the second most useful trait when all breeds are considered.

Regulation Of Metabolism During Feeding And Fasting

Cortisol (I) secreted by the liver derives from glycogen, and the remainder comes from gluconeogenesis, driven principally by glucagon. Although the rate of glucagon secretion is relatively low at this time, the decline in insulin enables the actions of glucagon to prevail. Growth hormone and cortisol are also secreted at relatively low basal rates in the postabsorptive period. About 75 of the glucose consumed by extrahepatic tissues during this period is taken up by brain, blood cells, and other tissues whose consumption of fuels is independent of insulin. Muscle and adipose tissue, which are highly dependent on insulin account for the remaining 25 . FFA gradually increase as adipose tissue is progressively relieved of the restraint imposed by high levels of insulin during the postprandial period. Blood glucose remains constant during this period, but glucose metabolism in muscle decreases as the restrictive effects of the glucose-fatty acid cycle become operative. Liver gradually...

Exercise and Immune Function

Aging affects the muscle precursor cells (satellite cells or myobloasts) and their regeneration after exercise (Grounds 1998). Aging may also affect proliferation and fusion of myoblasts in response to injury signaling molecules that stimulate satellite cells with aging host environment, inflammatory cells, growth factors and their receptors, and the extracellular matrix. There is a reduction in growth hormone, total and free testosterone, and cortisol, both at baseline and after exercise. The decreased anabolic effects on muscles may explain the loss of muscle mass and strength with aging (Hakkinen et al., 1998). The more primitive components of immune defense, including natural killer cells, phagocytes, acute-phase proteins, and regulatory cytokines, may be altered in elderly. Several investigators have found that the proportion of neutrophils will be increased in the circulation following physical exercise. An increase in neutrophils has been correlated with an increase in plasma...

Sequelae of Altered Metabolism in Visceral

Leptin is a hormone that is produced in the adipose cells and can act on the hunger center in the hypothalamus to reduce hunger and appetite and thereby lower food intake. Plasma leptin levels are correlated with body fat. Researchers have discovered a leptin receptor gene that is responsible for obesity due to the mutation or absence of the gene. This condition is extremely rare in humans. In general, in obese humans the leptin levels are elevated (hyperleptinemia). There is a progressive increase in plasma levels during puberty in girls due to the increase in body fat during this period and in response to the effect of estrogens. Circulating leptin levels tend to decrease in response to testosterone in boys, thus resulting in higher plasma leptin levels in women compared to men. Leptin levels are also affected by insulin and glucocorticoids.

Working Model For The Neural Circuitry Of Anxiety Disorders

Neural Circuits Anxiety Disorders

A biological model to explain pathological human anxiety should involve both brain stem circuits and cortical and subcortical regions involved in memory and modulation of emotion. The evidence is consistent with chronically increased function of neurochemical systems (CRF and NE) that mediate the fear response in anxiety disorders. Although it is clear that activity at the central portion of the HPA axis is increased, responses at other portions of the HPA axis, including the pituitary and adrenals, and the long-term effects on the hormonal final product (cortisol), are less clear. Increased NE and CRF released in the brain act on specific brain areas, including hippocampus, mPFC, temporal and parietal cortex, and cingulate, that are dysfunctional in human anxiety disorders. Other neurochemical systems, including Bzs, opiates, dopamine, CCK, and NPY, also play a role.

Regulation of Meal Size by Satiety Peptides and Adiposity Signals

Adiposity signals such as leptin act in conjunction with satiety signals in the brain during digestion and their concentration is determined in relation to the degree of adiposity. Like CCK, the effect on meal consumption and body weight of their exogenous administration is dose dependent. Leptin is a peptide hormone produced predominantly by adipocytes, and it is also secreted by the epithelial cells of the stomach. The definitive role of leptin in digestive physiology is still being determined, but it is thought to play a part in limiting food intake in conjunction with CCK. It is when the adiposity signals interact with, and influence, the satiety signals originating from the gut that an attempt at controlling energy intake and meal size is made.

Short Term Eating Behavior Is Set by Ghrelin and PYY336

Ghrelin is a peptide hormone (28 amino acids) produced in cells lining the stomach. It was originally recognized as the stimulus for the release of growth hormone (ghre is the Proto-Indo-European root of grow), then subsequently shown to be a powerful appetite stimulant that works on a shorter time scale (between meals) than leptin and insulin. Ghrelin receptors are located in the pituitary gland (presumably mediating growth hormone release) and in the hypothalamus (affecting appetite), as well as in heart muscle and adipose tissue. The concentration of ghrelin in the blood varies strikingly between meals, peaking just before a meal and

Clinical Presentation

Individuals in the vegetative state require a multi-disciplinary approach to patient care. Their course is frequented by extended hospital stays and multiple complications, such as pneumonia, decubiti, urinary incontinence, and urinary infection. In addition, patients may experience disordered neuroendocrine dysfunction with elevated profiles of growth hormone, prolactin, luteinizing hormone, and cortisol.

Adipose Tissue Stores and Supplies Fatty Acids

Adipose tissue, which consists of adipocytes (fat cells) (Fig. 23-16), is amorphous and widely distributed in the body under the skin, around the deep blood vessels, and in the abdominal cavity. It typically makes up about 15 of the mass of a young adult human, with approximately 65 of this mass in the form of triacylglycerols. Adipocytes are metabolically very active, responding quickly to hormonal stimuli in a metabolic interplay with the liver, skeletal muscles, and the heart.

Adrenal Incidentaloma

Laboratory studies are directed at ruling out a functional tumor and should include, at the minimum, a serum potassium level, a serum cortisol level, a 24 hour urine for 17-hydroxycorticosteroids and 17-ketosteroids, and a 24 hour urine for vanillylmandelic acid (VMA), catecholamines, and metanephrines. A low serum potassium level, especially in association with hypertension, in a patient not taking diuretics should lead to further specific studies to exclude or diagnose an aldosteronoma. Cushing's syndrome should be suspected with an increased serum cortisol level or an increased 24 hour urinary 17-hydroxycorticosteroid level. These findings should prompt use of low-dose and high-dose dexamethasone suppression tests to determine the presence of Cushing's syndrome and if Cushing's disease is the source. Elevated urinary levels of 17-ketosteroids suggest an adrenocortical malignancy. Increased urinary levels of VMA, catecholamines, and or metanephrines, especially in the face of...

Relevance Of The Autonomic Innervation Of The Pancreatic Islet

Another important function of the parasympathetic nerves is to stimulate glucagon secretion during hypoglycemia, which provides a mechanism for the recovery of circulating glucose. The protection against hypoglycemia is also achieved by other mechanisms, for example, the secretion of adrenaline and cortisol from the adrenals as well as direct stimulation of the release of glucose from the liver, but the primary involvement of glucagon in this respect has been established. The glucagon response to hypoglycemia is due to direct stimulation of glucagon secretion by the low glucose level and by the reduced intraislet concentration of insulin, and several studies have shown that the autonomic nerves also contribute to a major degree. Thus, ganglionic blockade is associated with more than 75 inhibition of the glucagon response to hypoglycemia in conjunction with lowered responses of markers for parasympathetic activation, as demonstrated both in humans and in experimental animals. In...

Neural Structures Critical to the Expression of Appetite

Substances crossing the blood-brain barrier entering the brain factors such as neurotransmit-ter precursors, leptin or insulin cross the blood-brain barrier and directly alter CNS neurochem-ical activity, particularly in key hypothalamic nuclei and associated limbic areas.

Cushings diseaseCushings syndrome

Diagnosis is by detection of an elevated plasma cortisol with lack of diurnal variation. Because other conditions can produce a similar pattern (e.g. excess alcohol production), a low dose Dexamethasone suppression test should be performed to confirm the diagnosis. Dexamethasone suppresses ACTH production but does not interfere with cortisol assay. Therefore, in a patient who does not have Cushing's syndrome, Dexamethasone, by suppressing ACTH, will suppress cortisol. If cortisol levels are not suppressed, the next step is to measure plasma ACTH (by a radio-immunoassay) and to perform a high dose Dexamethasone suppression test to determine suppression of urinary 17-hydroxy-corticosteroids.

Cyclic AMP Acts as a Second Messenger for a Number of Regulatory Molecules

Epinephrine is only one of many hormones, growth factors, and other regulatory molecules that act by changing the intracellular cAMP and thus the activity of PKA (Table 12-4). For example, glucagon binds to its receptors in the plasma membrane of adipocytes, activating (via a Gs protein) adenylyl cyclase. PKA, stimulated by the resulting rise in cAMP , phosphorylates and activates two proteins critical to the conversion of stored fat to fatty acids (perilipin and hormone-sensitive tri-acylglycerol lipase see Fig. 17-3), leading to the mobilization of fatty acids. Similarly, the peptide hormone ACTH (adrenocorticotropic hormone, also called corticotropin), produced by the anterior pituitary, binds to specific receptors in the adrenal cortex, activating adenylyl cyclase and raising the intracellular cAMP . PKA then phosphorylates and activates several of the enzymes required for the synthesis of cortisol and other steroid hormones. The catalytic subunit of PKA can also move into the...

The Hypothalamus And Neuroendocrine Regulation

Neurohumoral Regulation

A role for hypothalamic timing mechanisms in neuroendocrine regulation is predicted by the rhythmic profiles of hormone release by the anterior pituitary and its target organs. This is clearly exemplified by the temporal profile of cortisol secretion by the adrenal gland. Release of plasma corticosteroids is under control of the hypothalamic-pituitary-adrenal (HPA) axis and exhibits a circadian profile, with peak levels occurring at the end of the dark phase in humans and the end of the light phase in rat. Although the temporal relations of these peaks differ between the two species, the temporal association of the peaks to activity is the same. Release of corticosteroids from the adrenal is under the control of corticotropin-releasing factor (CRF) neurons in the paraventricular hypotha-lamic nucleus. Release of CRF into the portal plexus at the median eminence elicits the synthesis and release of adrenocorticotropin hormone from the anterior pituitary, which subsequently stimulates...

Body Energy Homeostasis

Of the LH and VMN have pronounced disturbances in fat metabolism (Friedman & Stricker, 1976). Animals with a VMN lesion show increased fat storage such that circulating levels of the metabolic products of fat metabolism are decreased. It has been proposed (Friedman & Stricker, 1976) that it is this decreased availability of the metabolic products of fat metabolism that stimulate food intake. Presently, in line with the idea that fat metabolism is crucial to body energy homeo-stasis, evidence suggests that peptides produced in the body and correlated with body fat mass are essential to the long-term control of food intake and body weight. Leptin is one such peptide. Leptin is the protein product of the ob gene. It is primarily produced in white adipose tissue, and the plasma level of leptin accurately reflects total-body adiposity (Friedman, 1997 Porte et al., 1998). It enters the brain from the circulation by a saturable transport mechanism (Friedman, 1997 Seeley & Schwartz,...

Psychobiological Structures of Shamanistic ASC

ASC of other shamanistic healers may involve soul journey, but typically have other psychophysiological and experiential dynamics. Possession ASC of mediums have characteristics of a take over of the person by spirits (Bourguignon, 1976 cf. Goodman, 1988 Lewis, 1988) and temporal lobe symptomology (tremors, seizures, convulsions, and amnesia) (Winkelman, 1986b, 1992). Possession is not a unitary phenomenon, but involves a variety of different psychodynamic processes including dissociation, illness, communication, role enactment, and political struggle (Boddy, 1994 Shekar, 1989). Possession ASCs predominantly occur in complex societies with hierarchical political integration and reflect the psychody-namics of oppression and powerlessness (Bourguignon, 1976 Winkelman, 1986b, 1992). Meditative ASC are characterized by deliberate relaxation (direct parasympa-thetic activation) and focus of attention. Castillo (1991) characterizes meditative practices as involving the differentiation of a...

Fresh Poultry Meat Composition and Nutritional Value

The fact that poultry meat is considered to be a source of lean meat and has a higher level of unsaturated fat as compared with red meat has resulted in a significant increase in poultry meat consumption in North America (Table 1) and around the world. Overall, the composition of poultry meat is dependent on species, strain, sex, age, and diet. Table 4 illustrates that species vary in their fat content. Turkey meat is usually lower in fat than chicken, while goose and duck meat are higher in fat. In poultry fat is deposited either under the skin or in the abdominal cavity. Therefore it is easy to obtain very lean poultry meat by separating the skin from the flesh. This is different from red meat where marbling or intramuscular fat deposits are visible within a meat cut and are difficult to separate from the lean muscle. The diet of the monogastric birds can also significantly affect the composition of the meat. Carcass fat content and composition is particularly sensitive to the type...

Hunger Physiological Determinants

Stomach distension and the detection of macro-nutrients such as fat or protein within the gut are all powerful satiety cues. They bring a meal to an end and for a time inhibit further consumption. Eventually, hunger again prevails and food intake follows. The flux between hunger and satiety is episodic and underpins the expression of our eating behavior throughout the day. However, it is not just the absence of episodic satiety cues (e.g., stomach distension and intestinal or absorbed nutrients) that influence the expression of hunger. Reduction in blood glucose levels or in levels of the circulating adipose tissue hormone leptin indicates a deficit in available energy and in energy reserves. Fluctuation of these factors indicates the metabolism and storage of the body's energy reserves. These are a tonic class of physiological signals that also influence the expression of appetite. Like episodic satiety signals, these tonic signals normally act on inhibitory mechanisms with the...

The Pig As A Model Of Omnivorous Mammals

In addition to these rapid, short-term control systems that operate in the time span of a meal, there are long-term controls that operate over days and weeks. An example is the leptin system. Leptin is released from body fat stores and acts centrally to inhibit eating. Over time, as the fat stores slowly increase, the levels of leptin increase. Leptin depresses food intake and limits body weight increase. Note that the controls of food intake are predominantly

Physiology and function

Carbohydrate metabolism is one of the core functions of the liver. As energy supply is not constant, the body has to adapt to irregular food intake by devising a system whereby energy can be stored and called upon on demand. The liver provides this function by storing glucose in the form of glycogen in hepatocytes. In situations where the body needs more energy than is currently being ingested or during times of fasting, glycogen is used for neogenesis of glucose. Even in unfavorable situations such as anaerobic metabolism, the liver will continue to provide energy by recycling lactic acid, a product of anaerobic metabolism, into glucose via the Cori cycle.7 The liver is also a key structure in fat and protein metabolism. Maintaining close communications with adipocytes via cell signaling pathways, the liver regulates fat storage and reabsorption as a more long-term storage of energy. By producing and breaking down amino acids, the liver is primarily responsible for maintaining...

Pathophysiology of Stone Formation

Other conditions predisposing to gall bladder disease Insulin-resistant diabetes predisposes to cholelithiasis. A Swedish study showed that the prevalence of gall stones in Crohn's disease was twice that seen in the general population. Cirrhosis is another major risk factor for gall stones. The incidence of gall stone formation in cirrhosis is 10 times that seen in the general population. The incidence increases with the severity of cirrhosis, being worse in Child's class B and C disease and in patients with higher body mass index. High estrogen level and reduced hepatic synthesis and transport of bile salts are reasons for the increased risk in cirrhosis. The Physicians' Health Study showed that 30 minutes of endurance-type exercise five times per week prevents approximately one-third of cases of symptomatic gall stones in men. The Nurses' Health Study confirmed the same trend in women.

Effects of Status Grand

Experimental models in animals provide evidence of the neurologic effects of SGM. Selective permanent cell damage in the hippocampus, amygdala, cerebellum, thalamus, and middle cerebral cortical layers develops after 60 min of seizure activity. Even with artificial ventilation and correction of existing metabolic derangements, most changes still occur. This cell death results from the increased metabolic demands and the exhaustion of the continuously firing neurons. In addition, there are secondary effects that probably exaggerate the adverse effects of SGM. After unremitting SGM, the cerebral P o2 and amounts of cytochrome A and cytochrome A3 reductase decrease, enhancing the risk of cell damage. Increases in calcium, arachidonic acid, arachidonic diglycerol, prostaglandin, and leukotriene levels in the neurons exaggerate or cause cerebral edema or cell death. Increased levels of cyclic AMP and increased release of prolactin, growth hormone, ACTH, cortisol, insulin, glycogen,...

Regulation of Transcription by Steroid Hormones

Steroid hormones (estrogen, progesterone, and cortisol, for example), too hydrophobic to dissolve readily in the blood, are carried on specific carrier proteins from their point of release to their target tissues. In target cells, these hormones pass through the plasma membranes by simple diffusion and bind to specific receptor proteins in the nucleus (Fig. 12-40). Hormone binding triggers changes in the conformation of the receptor proteins so that they become capable of interacting with specific regulatory sequences in DNA called hormone response elements (HREs), thus altering gene expression (see Fig. 28-31). The bound receptor-hormone complex can either enhance or suppress the expression of specific genes adjacent to HREs. Hours or days are required for these regulators to have their full effect the time required for the changes in RNA synthesis and

Abnormalities of Hormones and Other Circulating Factors

Syndrome, including abdominal obesity, insulin resistance, impaired glucose homeostasis, hypertension, and lipid abnormalities. These similarities led to the hypothesis that a dysregulation of the HPA axis in the form of functional hypercortisolism could potentially be a cause for abdominal obesity and its different metabolic consequences. High levels of emotional or physical stress are thought to increase cortisol secretion or turnover and thereby increase visceral obesity. Another potential mechanism involves the peripheral metabolism of cortisol. The enzyme 11- -hydroxysteroid dehydrogenase, which converts steroid precursors to cortisol, is expressed in adipose tissue. With increasing obesity, more cortisol is derived from cortisone in adipose tissue due to the increased activity of this hormone. Urine studies in obesity also show an increase in the ratio of tetra-hydrocortisol to tetrahydrocortisone, indicating a relative increase in the pathways leading to cortisol formation....

Development of immunosuppressive therapy

Duct drainage, splenectomy, thymectomy, anti-lymphocyte serum or globulin, and steroids. Corticosteroids are naturally occurring hormones secreted by the adrenal cortex, of which Cortisol (hydrocortisone) is by far the most powerful component known to possess lymphocytolytic activity, particularly with respect to T lymphocytes, to inhibit Ivm-phokine production, and to exert a stabilizing effect on the lysosomal membranes, along with those of other cellular organelles. These effects are dose- or concentration-dependent. Corticosteroids not only intervene at many points of the immune response, such as preventing lymphocyte recirculation and generation of antibody-producing and cytotoxic effector cells, but they also possess a remarkable antiinflammatory potency. They inhibit neutrophil adherence to the vascular endothelium at an inflammatory site and suppress monocytic functions such as microbicidal activity, monocyte response to lymphokines, and release of monokines. Antilymphocyte...

Clinical Description Dm1

Ninety percent of DM1 patients present at adulthood with delayed muscle maturation, distal muscle weakness, wasting, myotonia, cataracts, cardiac abnormalities, smooth muscle dysfunction, insulin resistance, daytime sleepiness, testicular atrophy (low reproductive fitness), ''difficult'' personality, neuropsychiatric disturbances, and frontal balding. 1 Ten percent of the patients present at infancy with hypotonia (floppy infant), oromotor dysfunction, tent-shaped mouth, feeding and respiratory insufficiency (diaphragmatic hypoplasia), arthrogryposis, and mental retardation in those who survive until adulthood (congenital DM). 1 All manifestations show a progressive course. Usually, creatine kinase is elevated. Muscle biopsy shows type 1 predominance, centrally located nuclei, severe fiber atrophy with nuclear clumps, hypertrophic and angulated fibers, and occasionally, necrotic fibers, fibrosis, or fat deposits. Cardiac involvement comprises conduction defects (mostly HV...

Harnessing the mutant map to ongoing genomics programmes

A draft human genome sequence is expected by year 2000. Plans to provide a draft sequence of the mouse genome have been initiated. In addition, the provision of finished sequence from several defined regions of the mouse genome is already underway. Comparison of human and mouse sequence in any region is expected to improve the identification and annotation of gene sequences and provide an important adjunct to gene prediction software. Indeed, in at least a few cases to date, the provision of mouse and human comparative sequence has underpinned the identification of novel genes and their mutation scanning. One recent example is the identification of the mouse X-linked Bare patches (Bpa) and Striated (Str) mutations (Liu et al 1999), both dominant male lethals having pleiotropic effects on skin morphology and skeletal development. Comparative sequencing of the region in which the Bpa and Str mutations were known to lie aided the characterization and annotation of a novel 3...

Macronutrients and Physical Activity Protein

Carbohydrate supplies about 45 of the energy in the typical Western diet this amounts to about 200300 g day-1 for the average sedentary individual, and is the amount that is necessary to get through normal daily activities. In an hour of hard exercise, up to 200 g of carbohydrate can be used, and sufficient carbohydrate must be supplied by the diet to replace the amount used. Replacement of the glycogen stores is an essential part of the recovery process after exercise if the muscle glycogen content is not replaced, the quality of training must be reduced, and the risks of illness and injury are increased. Low muscle glyco-gen levels are associated with an increased secretion of cortisol during exercise, with consequent negative implications for immune function.

Adrenal Insufficiency And Shock

Laboratory clues to the possible concomitant presence of adrenal insufficiency may be mild hypoglycemia, hyponatremia, hyperkalemia, and eosinophilia. Azotemia is, however, nonspecific and is often present in dehydration from any cause. In suspected cases, a serum cortisol should be drawn prior to steroid treatment.

Risk Versus Benefit Assessment

A good example of an application of mechanistic modeling in quantitative risk benefit assessments comes from the literature on inhaled corticosteroids (43,44). While inhaled corticosteroids present a viable therapeutic option for asthma, there have been questions on their long-term safety. Specifically, these concerns stem from their potential to suppress development of the adrenal function. Consequently, a clear delineation of the benefit (for asthma) and risk (clinical adrenal suppression) is necessary for development of newer inhaled cor-ticosteroids. Here the benefit is a conglomeration of all favorable attributes of a molecule, including optimal PK properties, drug delivery properties, and increased residence in the lung, which may likely contribute to a more favorable systemic side-effect profile. An assessment of a quantitative risk benefit value would entail the use of cortisol levels in plasma as a biomarker of the suppression in adrenal function. PK PD modeling can then be...

High Fat Diets and Obesity Possible Influence of n3 PUFAs

The peptide hormone insulin is produced in the pancreas and secreted in proportion to the degree of adiposity. Similar to leptin, insulin levels are correlated with amount of abdominal fat (Porte et al., 1998 Woods et al., 1996 Woods, Figlewicz Lattemann, Schwartz, & Porte, 1990 Woods et al., 1998). It is transported into the brain where it acts to decrease food intake and body weight (Schwartz, Figlewicz, Baskin, Woods, & Porte, 1992 Woods et al., 1996). High insulin resistance is a characteristic of obesity, hypertension, and non-insulin-dependent diabetes mellitus. There is an inverse relationship between insulin action and triglyceride content. With the ingestion of fat, insulin secretion is increased. Insulin stimulates fatty acid synthase, an enzyme that catalyzes all reactions involved in lipogenesis, and thereby results in the accumulation of triglycerides (Sul, Latasa, Moon, & Kim, 2000). Monounsaturated fatty acids (such as oleate) and saturated fatty acids (such as...

Deficient Secretion

Hypoadrenalism (Addison's disease) can be either primary or secondary. Primary hypoadrenalism is caused by a failure of the adrenal cortex as a consequence of auto-immune disease, infection or surgery. As a consequence, ACTH levels are high because of a low circulating cortisol level. Melanocytestimulating hormone (MSH) is secreted in conjunction with ACTH leading to the characteristic pigmentation of the skin and buccal mucosa. Secondary hypoadrenalism results from reduced levels of ACTH following damage to the anterior pituitary. The deficiency in both mineralocorticoids and glucocorticoids results in characteristic clinical features Abnormal fat deposits across the upper back (buffalo lump) and in the face (moon face)

Affective disorders of childhood and adolescence

There is much controversy regarding the occurrence of major depressive disorder in prepubertal children. However, several studies in both the United States and Britain have suggested that depressive disorder does exist, although the frequency appears to be lower than in adolescents. There is endocrinological evidence, based on the hypersecretion of cortisol and an abnormal growth hormone response to insulin-induced hypoglycaemia, to suggest that children with major depressive disorder show similar endocrine abnormalities to those of adolescents and adults. However, the number of patients in these studies is small and clearly more thorough investigations must be undertaken before any conclusion may be reached.

Hypothalamic PituitaryAdrenal Axis

Cortisol has been recognized as a stress-response hormone because plasma levels are altered by environmental stress. Disturbances in the hypothalamic-pituitary-adrenal (HPA) axis due to mood disorders in humans were reported as early as 1943 by Pincus and Hoagland, who observed an elevation of urinary metabolites of adrenocortical secretion related to stress among test pilots. In response to anxiety or depression, an increase in norepinephrine (NE) activates the hypothalamus to release corticotropin-re-leasing factor, which stimulates the secretion of adrenocorticotropic hormone. This hormone stimulates the adrenal cortex, thereby increasing plasma concentrations of cortisol. By a negative feedback mechanism, cortisol lowers the levels of NE synthesis. The best known challenge test related to mood disorders is the Dexamethasone Suppression Test. A level of > 5 mg dl of cortisol at 8, 16, or 24hr after dexamethasone administration is abnormal and indicates a lack of suppression...

Structure of the CSFs

The CSFs are small polypeptides of Mr around 15 000 which are heavily and variably modified by glycosylation, although the functional significance of this carbohydrate has not been established. IL-3, IL-5, GM-CSF, G-CSF erythropoietin, thrombopoietin and IL-11 are monomers, whereas CSF-1 and SLF are homodimers, linked by disulfide bonds. As discussed below, CSF-1 and SLF also differ from the other CSFs in binding to a different structural class of cell surface receptors. Although there are few similarities in the amino acid sequences of different CSFs, analysis of their three-dimensional structures has revealed that they all belong to one structural family of proteins, characterized by four a helices, bundled in a particular way. This family also includes most interleukins, as well as hormones such as growth hormone, thrombopoietin, erythropoietin and leptin. IL-2, erythropoietin, IL-4, IL-5, IL-6 and IL-7, as well as other cytokines such as LIF, CNTF and leptin.

Neuroendocrine Theories

Approximately 40-60 of depressed individuals produce and secrete excessive amounts ofcortisol, primarily during the afternoon and evening. In these patients, cortisol secretion returns to normal levels after the depressive episode remits. This excessive cortisol is thought to be due to the overproduction by the hypothalamus of corticotropin-releasing hormone (CTRH), a compound that is stimulated by norepi-nephrine and acetylcholine, leading some to believe that CTRH and the noradrenergic system may be interconnected. Administration of dexamethasone, a chemical that temporarily suppresses the production of cortisol in nondepressed adults, was at one point believed to be a useful tool in the diagnosis of depression since many depressed individuals did not demonstrate this cortisol suppression. Recent evidence has indicated that many nondepressed psychiatric patients also fail to display a response to the dexame-thasone suppression test, thus limiting its utility in the diagnosis of...

Regulation of Glucocorticoid Activity

The most important stimulus for the secretion of cortisol is the release of ACTH from the anterior pituitary. ACTH release is promoted by hypothalamic release of corticotrophin releasing hormone (CRH) into the hypophyseal portal blood. Cortisol exerts a direct negative feedback control with inhibition of both CRH and ACTH release. Glucocorticoid secretion is also modulated by a normal circadian pattern whereby cortisol levels peak in the early morning and reach a trough in the middle of the night. Stress is also a modulatory factor and the stress associated with the peri-operative period can override the normal negative feedback control mechanism. Large doses of opioids may attenuate the stress response to surgical stimulation. The drug etomidate inhibits cortisol synthesis and has previously been shown to have an adverse effect on outcome when used for sedation on intensive care units. Patients on regular glucocorticoid replacement therapy require increased dosage during periods of...

Depletion of Muscle Glycogen

The levels of muscle glycogen at slaughter are a result of the cumulative stressors that occur from the farm or feed-lot, through transport and lairage to the point of slaughter. Stressors can be classified as psychological if the levels of glycogen are affected by increased levels of adrenaline, producing a concomitant increase of corticosteroids, or physical if they involve physical exercise, sickness, or inadequate nutrition. In the case of physical exercise such as rounding up sheep and cattle, mounting behavior in cattle, or swim washing for sheep, the muscle glycogen is quickly converted to lactic acid, which is transported away from the muscles by the circulation. This lactic acid ultimately can be resynthesized to muscle glycogen, given sufficient time. Feeding immediately preslaughter helps some species, such as pigs, to replenish their muscle glycogen, as the ingested high energy carbohydrate can rapidly be reincorporated into muscle glycogen. In ruminants, however, the...

TABLE 1253 Clinical Signs of Hypoglycemia

Aberration than a true pathologic syndrome.24 It usually presents in children less than 18 months of age after a period of fasting. Often this is seen on holidays and weekends, when parents sleep late, inadvertently extending the child's usual nighttime fasting period. It is also more common during illnesses preventing normal food intake. These children return to normal after a glucose load and have no suspicious findings in either their history or physical exams. 25 Classically, this problem was thought to arise because these children were small for age, but that idea has been called into question by more recent findings. 24 Currently, alanine, by far the most important amino acid in gluconeogenesis, is thought to play a major role in this disorder. 36 Haymond et al.5 demonstrated lower serum alanine concentrations in these patients as compared with age-matched control groups during fasting. Giving gluconeogenic precursors to these patients during periods of fasting prevents...

Adrenocortical Cancer

Laboratory findings include elevated urinary levels of dehydroepiandrosterone (DHEA) in the majority of patients. DHEA has minimal direct biologic activity, but is converted into active androgens in the periphery. Elevated plasma and urinary levels of cortisol are frequently seen. Elevated urinary levels of 17-ketosteroids, the breakdown product of both cortisol and androgens, can be found as well. It is rare to find elevated levels of aldosterone alone in adrenocortical cancers. It is more common to find a combination of increased hormone levels. Those tumors that have no hormonal activity usually present at a later, more advanced stage, are usually less differentiated, and portend a poor prognosis. cortisolism, as the remaining gland may be functionally suppressed. A mechanical bowel prep should be performed since the tumor may involve or invade the colon.

Refractory shock The role of steroids

The evidence for the use of steroids in the treatment of severe sepsis has gone full circle in the last 20 years, with recent interest focusing on low doses. In patients with severe sepsis there are complex effects on the hypothalamic-pituitary-adrenal axis. On the one hand there is stimulation of the axis and loss of negative feedback control, which usually leads to high adrenocorticotrope hormone (ACTH) and cortisol levels. On the other hand various mediators cause adrenal suppression and glucocorticoid resistance. With time ACTH levels may fall due to inhibition or pituitary depletion - this leads to relative adrenal suppression. Recent studies have shown that patients with sepsis who are dependent on vasoactive drugs may benefit from stress doses of hydrocortisone (50-100 mg intravenously 4 times a day for 7 days). A proportion of these have relative adrenal insufficiency as defined by the short synacthen test and these patients have the greatest benefit in terms of mortality....

Glucosefatty Acid Cycle

The self-regulating interplay between glucose and fatty acid metabolism is called the glucose-fatty acid cycle. This cycle constitutes an important biochemical mechanism for limiting glucose utilization when alternative substrate is available, and conversely limiting the consumption of stored fat when glucose is available. Fatty acids that are produced in adipose tissue in an ongoing cycle of lipolysis and reesterification may either escape from fat cells to become the free fatty acids, or they may be retained as triglycerides, depending on the availability of -glycerol phosphate (Fig. 1). The only source of -glycerol phosphate for reesterification of fatty acids is the pool of triose phosphates derived from glucose oxidation, because adipose tissue is deficient in the enzyme required to phosphorylate and hence reuse glycerol released from triglycerides. Consequently, when glucose is abundant, -glycerol phosphate is readily available, the rate of reesterification is high relative to...

Underlying Factors Glucocorticoids

Maternal glucocorticoids can also influence birth weight of the offspring. Under normal conditions, fetal exposure to glucocorticoids is relatively low due to the presence of placental 11 3-hydroxysteroid dehydrogenase 2 (11 HSD2), an enzyme that acts as a placental barrier by inactivating maternal glu-cocorticoids before they cross into the fetal environment. Maternal glucocorticoid treatment during pregnancy or inhibition of the placental 11 3HSD2 can therefore increase the amount of active gluco-corticoid crossing the placenta. Excess glucocorti-coid exposure has also been implicated in disturbing the normal growth and development of the fetus with consequential effects on the overall health of the adult offspring. There does, however, appear to be a critical window of sensitivity where the developing fetus is particularly sensitive to glu-cocorticoids. Glucocorticoid overexposure in the 3rd trimester is known to cause reductions in birth weight. Studies in rats have established...

Well Being and Handling

Physiological measures such as cortisol in the blood can also be used as indicators of fear stress that occurs during nonpainful restraint in a squeeze chute. 4 Cortisol is a time-dependent measure and it takes 10 to 20 minutes for it to reach peak levels. It is important to differentiate between fear and pain stress. Cortisol levels can also rise in response to pain from procedures such as hot iron branding. The variable of the handling stress needs to be separated from the variable of pain caused by a procedure such as castration. Handling stress is mostly fear, and stress from castration is caused by pain and injury to tissues. Fear stress during handling can vary from almost none to extreme. Extensively raised cattle that were not accustomed to close contact with people had much higher cortisol levels when they were restrained in a squeeze chute compared to hand-reared dairy cattle. 5 Taming of an animal may reduce physiological reactivity of the nervous system. Hand-reared deer...

Factors Affecting Metabolic Rate

The process of oxidation involves a series of enzyma-tically controlled biochemical reactions leading eventually to the combination of oxygen with the carbon and hydrogen components of the body's fuels to yield the carbon dioxide and metabolically derived water. The incompletely oxidized nitrogen is excreted as urea, which is synthesized by the liver and excreted by the kidneys. The intermediate steps in the metabolism of the body's fuels are linked biochemically to drive the generation of phosphate-containing organic molecules, such as adenosine triphosphate (ATP), which in turn serve as the direct energy sources for all the body's cell activities, including the synthesis of complex molecules, the maintenance of tightly controlled ionic gradients in the cell, and the excretion of ions and molecules outside the cell. Thus, the oxygen being taken up by the lungs reflects the tissue metabolism of the fuels needed to regenerate the ATP used up in either biochemical 'internal' work or...

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