How to Grow Taller

5 Inch Height Gain

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Congenital multiple pituitary hormone deficiencies MPHD including growth hormone

In 1988, we had the opportunity to examine six out of 10 living dwarfed patients, part of 24 related patients recorded on the island of Krk in the Adriatic Sea. They belong to two villages near to each other, and were known to have existed since the end of the 19th century (Hanhart 1925). DNA from these patients revealed a mutation in the PROP1 gene (a transcription factor) causing MPHD (thyroid-stimulating hormone, prolactin, luteinizing hormone, follicle-stimulating hormone and GH deficiencies) (Krzisnik et al 1999). They were treated by thyroxine, which some took irregularly. Only one 14 year old girl received GH. The five adult patients ranged from 47 to 68 years (3 males, 2 females). In addition to short stature (120 139 cm), they were obese, sexually immature and had a very wrinkled skin (Fig. 1). Notably the patients did not have any grey hair despite their advanced adult age. This was also seen on a picture of a 70 year old patient found on his tombstone (Fig 2). The...

Effects of Growth Hormones on Carcass Composition

Hormonal effects are important in controlling body composition, as shown by the differences between entire males and castrates. These effects can also be achieved by exogenous administration of hormones, through implants behind the ear in the case of estrogens and androgens, and via the diet in the case of p-adrenergic agonists. Growth hormone must be given by intramuscular injection. All these materials are effective in changing body composition, although they are not allowed in the European Union because of the potential safety risk. This also applies to lamb imported into the European Union. Ralgro, a compound with estrogenic effects, is licensed for use in the United States, but is not widely used at present. It appears that the use of hormones for controlling body composition in sheep is much less common than in beef and is likely to reduce further under pressure from consumers.

Effects of growth hormone and insulinlike growth factor 1 deficiency on ageing and longevity

Abstract Present knowledge on the effects of growth hormone (GH) insulin-like growth hormone (IGF)1 deficiency on ageing and lifespan are reviewed. Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGF1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. These changes do not seem to affect the lifespan, as patients reach old age. Animal models of genetic MPHD (Ames and Snell mice) and GH receptor knockout mice (primary IGF1 deficiency) also have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting large amounts of GH have premature death. In conclusion longstanding GH IGF1 deficiency affects several parameters of the ageing process without impairing lifespan, and as shown in animal models prolongs longevity. In...

Growth Hormone

Basal and pulsatile secretion of growth hormone (GH) is increased, with a peripheral resistance to its effects. Serum GH levels are elevated in 60 of patients, particularly in the most severe cases. This is due to decreased feedback from lowered serum concentrations of insulin-like growth factor 1 (IGF 1) and to increased serum levels of ghrelin. Growth hormone levels do not rise normally after L-dopa or insulin hypoglycemia, but there may be an unexpected rise in GH blood levels after stimulation with thyrotrophin-releasing hormone.

Growth hormone axis

In the acute phase circulating levels of growth hormone (GH) are elevated. The peak GH levels as well as interpulse concentrations are high (Ross et al 1991, Voerman et al 1992) and the GH pulse frequency is increased. Serum insulin-like growth factor (IGF)1 concentrations are low, (Ross et al 1991). The combination of high GH levels and low IGF1 levels has been interpreted as resistance to GH, which may be related to decreased GH receptor expression (Hermansson et al 1997). The other GH-dependent peptides IGF binding protein (IGFBP)3 and acid labile subunit (ALS) are also decreased in the circulation (Baxter 1997, Timmins et al 1996), preceded by a drop in the GH binding protein (GHBP). Circulating levels of the small IGFBPs such as IGFBP1, IGFBP2 and IGFBP6 are elevated (Baxter et al 1998, Rodrigues-Arnao et al 1996). It has been suggested that these changes are brought about by the effects of cytokines such as tumour necrosis factor (TNF)a, interleukin (IL)1 and IL6. The hypothesis...

Mechanisms of conjoint failure of the somatotropic and gonadal axes in ageing men

Endogenous growth hormone (GH) production falls by 50 every 7 years and bioavailable testosterone concentrations decline concomitantly by 12 15 every decade in ageing men. Despite this temporal parallelism, the neuroendocrine bases of the somatopause and gonadopause are not known. This knowledge deficit contrasts with the recent unfolding of new insights into the nature of oestrogen-dependent control of the GH insulin-like growth factor (IGF)1 axis in pre- and postmenopausal women. The present overview examines the postulate that the pathophysiology of somatopause and gonadopause in ageing men is bidirectionally linked. According to this broader thesis, hyposomatotropism accentuates Leydig cell steroidogenic failure and, conversely, progressive androgen deficiency exacerbates the decline in GH IGF1 output in ageing. Clinical features of ageing include variably impaired psychological well being, cognitive function and quality of life decreased libido and or sexual function...

Endocrinology of ageing

The third endocrine system that gradually declines in activity with ageing is the growth hormone (GH) insulin-like growth factor 1 (IGF1) axis (Corpas et al 1993). Mean pulse amplitude, duration, and free fraction of GH secreted, but not pulse frequency, gradually decrease during ageing. In parallel, there is a progressive fall in circulating IGF1 levels (Corpas et al 1993). The IGF1

Endocrine aspects of healthy ageing in men

Frailty is characterized by generalized weakness, impaired mobility and balance and poor endurance. Loss of muscle strength is an important factor in the process of frailty, and is the limiting factor for an individual's chances of living an independent life until death. In men, several hormonal systems show a decline in activity during ageing. Serum bioavailable testosterone and oestradiol, dehydroepiandrosterone and its sulfate, and growth hormone and insulin-like growth factor 1 concentrations all decrease during ageing in men. Physical changes during ageing have been considered physiologic, but there is evidence that some of these changes are related to this decline in hormonal activity. Studies on hormone administration in the elderly appear to be promising. However, until now, hormone replacement has not yet been proven to be beneficial and safe.

Androgen effects

Following the adage that when one's only tool is a hammer, remarkably soon all problems turn into nails, it is an understandable that androgen administration is proposed for older men. Such proposals long pre-date the first availability of testosterone (Hamilton 1937) with many bouts of rejuvenation quackery associated with the names of Brown-Sequard, Steinach and Voronoff into the early 20th century. Standard clinical endocrine practice includes replacement therapy for unequivocal hormonal deficiencies of the pancreas (insulin), thyroid (thyroxine), adrenal (glucocorticoid, mineralocorticoid) and gonads (oestrogen, androgen). Conversely, hormone replacement is not provided for other classical hormones such as prolactin, glucagon, somatostatin, calcitonin, calcitonin-gene related peptide and adrenalin, and other hormones (thyroid-stimulating hormone, LH, FSH, parathyroid hormone) are not replaced but substituted by simpler non-peptide end products. Generally, the criteria for a...

Zinc and Other Minerals

Unusual to find a documented case of clinical zinc deficiency apart from occasional cases of acroder-matitis enteropathica, there has been recent concern over the possibility of relative zinc deficiency, especially among chronically ill patients with excessive intestinal secretions. Zinc deficiency could lead to impaired taste (hypogeusia) and appetite and immunodeficiency as well as affecting growth. A large group of adolescents in Shiraz, Iran was described to be of very short stature because of dietary zinc deficiency. Similarly, a group of people in Keshan, China was found to develop cardiomyopathy because of a selenium deficiency in the soil. Iodine deficiency is surprisingly common worldwide, perhaps involving up to half of the world population or 3 billion people, especially in areas of Southeast Asia where it is not supplemented in salt. It may cause hypothyroidism, goiter (neck masses), cretinism, or impaired intelligence if severe.

Nutrition And Feeding

Complete rations contain added vitamins and minerals. Purified amino acids, binders, carotenoids, and antioxidants are other components found in many feeds. Growth hormone and antibiotics are sometimes used. Regulations on the incorporation of hormones along with other chemicals and drugs into aquatic animal feeds are in place in the United States and some other countries (Table 6). Few such regulations have been promulgated in developing nations.

TABLE 2316 Causes of Hypomagnesemia

The normal renal threshold for magnesium (1.5 to 2.0 meq L) is significantly decreased by cisplatin, diuretics, hypercalcemia, growth hormone, thyroid hormone, and calcitonin. Cisplatin causes dose-dependent, cumulative, reversible renal tubular injury. Even when the glomerular filtration rate is not diminished by cisplatin, renal magnesium wasting along with a secondary hypocalcemia and hypokalemia may develop. Potassium wasting is thought to occur as a result of impaired ATP production when magnesium is low. This in turn impairs the function of the membrane Na+ K+ transport system and causes loss of the normal Na+ K+ gradient. The accompanying hypocalcemia may be due to (1) impaired PTH release by the parathyroid gland, (2) decreased peripheral sensitivity to PTH, or (3) abnormal blood-bone calcium balance independent of PTH.

Adjunctive Treatments

There is great interest in a pharmacological role for growth hormone (GH) and or IGF-1 in reversal of the catabolic state and stimulation of anabolic processes. GH stimulates production of IGF-1, which improves amino acid transport and enhances glu-coneogenesis from exogenously supplied amino acids. Blood levels of IGF-1 are markedly reduced in burn patients following injury and remain so for the first week, after which levels increase these changes correlate with IGF binding protein-3 levels. This binding protein prevents plasma proteolysis of IGF-1. GH and IGF-1 have both been used in experimental models of burn injury, and their effectiveness at limiting catabolism and enhancing mucosal proliferation is encouraging. In children GH treatment accelerates donor site healing and increases protein synthesis. GH has also been shown to exert immunomodulatory effects, which may contribute to a reduced incidence of infection. Other growth factors have also been used experimentally and in...

Singlecopy nuclear genes

Meyer et al. (1994a) developed primers for the porcine growth hormone gene in order to detect 2 or less pork in beef. Using the TaqMam , or 5'-nuclease assay, Laube et al. (2001) have described a quantitative PCR assay of the bovine phosphodiesterase gene. As positive control, an amplification was carried out with primers specific for conserved regions of the mammalian and avian myostatin genes.

Biochemical Mechanisms of Action

In the plasma, increased levels of -endorphin, epinephrine, norepinephrine, corticosterone, ACTH, renin, and angiotensin I and decreased levels of growth hormone, thyroxine, triiodothyronine, and thyrotropin were reported with high caffeine doses. The mechanisms responsible for these various effects are largely unknown, and the mediation of adenosine receptors is suggested. The antagonism of benzodiazepine at the receptor level is observed at lower caffeine concentrations (0.5-0.7mM) than those required for phosphodiesterase inhibition.

Behavioral Regulation Of Immunity

Although immune responses can readily occur and be analyzed in vitro, the immune system normally functions in an intact organism where it has the opportunity to interact with other physiological systems. A significant body of recent data points out that indeed such interactions do occur in vivo. For example, the central nervous system (CNS) is in dynamic communication with the immune system. Lymphoid tissues are richly innervated, and abrogation of this sympathetic innervation alters expression of natural and acquired immunity. Cells of the CNS produce proinflammatory cytokines (e.g. interleukin-1 (IL-1) and IL-6), and mitogen- or antigen-stimulated lymphocytes produce different hormones (e.g. proopiomelanocortin-derived peptides, growth hormone, prolactin, luteinizing hormone) and neuropeptides (e.g. substance P, vasoactive intestinal peptide). Lymphocytes and macrophages

Psychosocial Deprivation

A few studies suggest the growth problem in PSD can be linked to neuroendocrine abnormalities secondary to stress. Levels of growth hormone and adrenocorticotrophic hormone have been low in some children studied in their adverse environments. Changes to loving, caring, and stimulating environments result in rapid resolution of the endocrine abnormalities.

Structures of cell surface receptorligand complexes

The structures of several receptor-ligand complexes have also been reported (see Table 1). For immune cell surface receptors, ligand-induced receptor oligo-merization is a major determinant of signal transduction. Figure 3 compares the structures of the complexes involving human growth hormone (hGH) receptor (hGHR) and the 55 kDa tumor necrosis factor (TNF) receptor (TNFR).

Iatrogenic Transmission Of Creutzfeldtjakob Disease

Over the last three decades, approximately 270 cases of iatrogenic CJD have been observed. 11 By far, the most frequently involved medical interventions were the surgical use of dura mater grafts (114 cases) and treatment with pituitary-derived human growth hormone (139 cases). In a few cases each, treatment with pituitary-derived gonadotropin, corneal transplantation, or the use of neurosurgical equipment such as stereotactic electrodes was implicated.

Diagnostic Potential Of The M129v Polymorphism

Although all vCJD cases investigated so far have been found to be M M homozygous at codon 129, the deferral of such potentially higher risk donors from blood or plasma donation is not feasible based on the already strained supply of these products and the large proportion of the population displaying this genotype. Also, any risk associated with the use of these products remains purely hypothetical at this point, and again there is mounting evidence against any risk being associated with their use. 14 However, for products carrying an identified level of risk and are needed in lower quantities, exclusion based on an identified genetic predisposition for disease development might be an option. Human growth hormone from cadaveric pituitary glands, a product that has historically led to many CJD transmissions, has already been replaced by recombinant versions of the product. Dura mater, another of the products implicated earlier, 11 is no longer in clinical use and has been widely...

Physiology of Normal Blood Glucose Regulation

The metabolic fate of ingested glucose is determined by the interplay of multiple hormones. Insulin is of major importance in this homeostasis, but glucagon, glucocorticoids, catecholamines, and growth hormone also have significant effects that are interactive with insulin. Glucose ingested with a meal or derived from the digestion of other dietary carbohydrates is rapidly absorbed by the small intestine. It is carried first to the liver by the portal vein, where a substantial portion (30-70 ) is removed the remainder enters the peripheral circulation, where regulated insulin secretion and target tissue responses to insulin contribute to glucose clearance and control of blood glucose levels (Figure 1).

Revolution in Biology

The fusion of traditional industrial microbiology and genetic engineering in the late 1970s led to the development of the modern biotechnology industry. Using recombinant DNA technology, this industry has brought a long and steadily growing list of products into the marketplace. Human insulin produced by genetically engineered bacteria was one of the first of these products. It was followed by human growth hormone an anti-viral protein called interferon the immune stimulant called interleukin 2 a tissue plasminogen activator for dissolving blood clots two blood-clotting factors, labeled VIII and IX, which are administered to hemophiliacs and many other products.

Receptor structure five major families

The hematopoietic receptor family (cytokine receptor class I) forms the largest group of cytokine receptors. This family includes the receptors for IL-2 IL-15 (3 chain), IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-11, IL-12, IL-13, GM-CSF (granulocyte-macrophage colony-stimulating factor), G-CSF (granulocyte colony-stimulating factor), OSM (oncostatin M), LIF (leukemia inhibitory factor), GH (growth hormone), Epo (erythropoietin), prolactin, CNTF (ciliary neurotropic factor), thrombopoietin (c-mpl) and CT-1 (cardiotropin 1), as well as nonligand binding accessory subunits such as the common gamma (yc) chain, gpl30 and KH97 (see below). These receptors all share a degree of structural homology in their extracellular domains, and in particular have a number of conserved cysteine residues. In addition, the extracellular domains express one or two copies of a common pentameric motif, Trp-Ser-X-Trp-Ser, contained within a fibronectin type III domain. The precise role this motif plays in...

Functions of soluble receptors

SRs that may assist the function of their ligands (Figure 1(3)) IL-4 dissociates from its SR much more rapidly than from its cell surface receptors. The soluble IL-4 receptors also provide 11.-4 with protection against proteolytic degradation. Therefore, although at high concentrations these receptors can interfere with IL-4 function, it seems likely that at their physiological levels the soluble IL-4 receptors actually serve as carriers of IL-4 in the circulation and facilitate its presentation to the cell-bound receptors. A similar role was ascribed to the soluble form of the growth hormone receptor (the growth hormone-binding protein). This SR is believed to increase the functional duration of its ligand by withholding its clearance from the circulation. The soluble TNF receptors are also found to increase the functional duration of their ligands, though by a different mechanism they prevent dissociation of the trimeric TNF molecules into inactive monomers and thus, despite their...

Clinical Description

This rare condition is inherited as an autosomal recessive condition. The clinical picture is characterized by premature rupture of the membranes, extreme skin fragility and laxity, easy bruising, large fontanels, umbilical hernia, short stature and characteristic facies with epi-canthic folds, downslanting palpebral fissures, puffy eyelids, blue sclerae, and micrognathia. During childhood and puberty, increased bruising and severe skin fragility predominate the clinical picture. Wound healing is not delayed and initial scar formation is only minimal. 19 In older patients, however, more typical atrophic scarring with pigmentation is seen, probably because of repeated skin tearing and bruising. Joint hypermobility, although not obvious during the first years of life, seem to become more important with age. Fragility of internal tissues is an important feature during childhood, as is illustrated by spontaneous bladder rupture at the age of 5 years in two children with the...

Laboratory Investigations

Increased growth hormone levels with decreased levels of insulin-like growth factor 1 (somatomedin C) in the serum. Plasma renin activity and aldosterone levels may be very high in patients who abuse laxatives or diuretics (pseudo-Bartter's syndrome). Electrocardiography shows sinus bradycardia, flat

Appropriate Uses of Gene Therapy

How do researchers determine which disorders or traits warrant gene therapy Unfortunately, the distinction between gene therapy for disease genes and gene therapy to enhance desired traits, such as height or eye color, is not clear-cut. No one would argue that diseases that cause suffering, disability, and, potentially, death are good candidates for gene therapy. However, there is a fine line between what is considered a disease (such as the dwarfism disorder achondroplasia) and what is considered a trait in an otherwise healthy individual (such as short stature). Even though gene therapy for the correction of potentially socially unacceptable traits, or the enhancement of desirable ones, may improve the quality of life for an individual, some ethicists fear gene therapy for trait enhancement could negatively impact what society considers normal and thus promote increased discrimination toward those with the undesirable traits. As the function of many genes continue to be discovered,...

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'').

Membrane Transporters

Excipients have been shown to be effectively transported in vitro across CaCo2 cell layers, as well as in vivo in humans. For example sodium N- 8-(2-hydroxybenzoyl) amino hcaprylate enables oral heparin absorption via transcellular pathway (52). Other N-acylated amino acids have also been successfully used for a number of macro-molecules including insulin, human growth hormone, and parathyroid hormone (53).

Genetic Engineering and Society

Policies were used to restrict immigration of certain Asian and European populations that were termed genetically inferior. Eugenics had its ultimate expression when it provided the scientific basis for the racial policies of the Nazis before and during World War II. Where the capability exists, so will the temptation. Will parents seek to amplify the gene for human growth hormone in their offspring so that their children could become heftier football linemen or taller basketball players The ability to select the gender of one's offspring by amniocentesis and abortion is already causing problems in some cultures.

Summary And Conclusions

L. monocytogenes has been recognized as a human pathogen for more than 50 yr. It primarily causes abortion, infections of the central nervous system or septicemia, mainly in certain well-defined high-risk groups, including immunocompromised persons and pregnant women. The widespread use of immunosuppressive medications for treatment of malignancy and management of organ transplantation, has expanded the immuno-compromised population at increased risk of listeriosis. Also consumer life styles have changed with less time for food preparation, more ready-to-eat, and take-away foods. Changes in food production and technology have led to the production of foods with long shelf life that are typical Listeria risk foods, because the bacteria have time to multiply, and the food does not undergo a listericidal process such as cooking before consumption. Increased mass production means outbreaks can change from being small and confined to a community or region, to large, affecting hundreds of...

Concerns Related to the Glycemic Index

Wolever attributed the differences in the glyce-mic response to a second meal during the postprandial period to differences in intermediary metabolism and insulin action associated with rapidly and slowly absorbed carbohydrates. Rapidly absorbed carbohydrates produce large increases in blood insulin levels that result in blood glucose levels decreasing sufficiently quickly to stimulate several counterregulatory hormones that inhibit insulin action and glucose disposal. Both carbohydrate drinks and meals consumed rapidly rather than sipped or eaten slowly are associated with significantly higher serum concentrations of glucagon, catecholamines, growth hormone, and nonesterified fatty acid (NEFA) levels postprandially. The addition of guar to a meal, which slows glucose absorption and lowers the glycemic response, reduces postprandial NEFA and ,3-hydroxybutyrate levels and improves insulin action. In contrast, nibbling high glycemic index

Maternal Endocrine Influences on Fetal Growth

Changes in maternal circulating growth hormone and growth hormone-like peptides such as placental lactogen, which increase during pregnancy, have combined effects that induce maternal insulin resistance and lead to higher circulating concentrations of glucose and lipids. These in turn are transported in increased amounts to the fetus where, combined with their stimulatory effects on fetal insulin and IGF1 and IGF2, promote fetal adiposity (or macro-somia, as in the infant of the diabetic mother) and

Anthropometric Assessment

At approximately the age of 6 months, when growth starts to become regulated by growth hormone, growth velocity usually begins to show a marked reduction from normal levels. Although for the Down's syndrome child the period between birth and 2 years and the period between 6 years and 10 years of age are times of accelerated growth, the deviation from normal levels remains significant. Slow growth velocity is also a particular feature of adolescence, although there is a pubertal growth spurt. The deviation of adult stature from the means of reference groups is greater than the deviations in early infancy. The short stature in Down's syndrome seems to be mainly the result of impaired growth of the long bones of the leg, because sitting height measurements show that the growth of the vertebral column is closer to normal. advanced. Both human growth hormone therapy and zinc sulfate supplementation of the diet have been reported to accelerate growth.

Nutritional Management

Long-term management of patients with PWS presents unique evolving nutritional challenges. During infancy, muscle hypotonia impairs oral feeding and causes inadequate caloric intake and failure to thrive. The combination of altered body composition (with diminished metabolically active lean mass), growth hormone

Molecular characterization of IL2

IL-2 belongs to the hematopoietin family which includes growth hormone, prolactin, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-11, IL-13, IL-15, GM-CSF, etc. The IL-2 gene, located on chromosome 4 (q26-q27), contains four exons coding for a 153 amino acid precursor including a 20 amino acid leader sequence. Human IL-2 contains only one O-glycosylation site (Thr3) glycosylation at this site is heterogeneous but does not affect biological activity. The three-dimensional structure of IL-2 is essentially composed of four a helices (A, BB', C and D) connected by three loops (Figure 1). A disulfide bridge between Cys58 and Cysl05 is necessary for the bioactivity of the molecule. The regions of the molecule involved in binding to the three chains of the

Metabolic Functions

In the pituitary gland, thyroid hormones, along with many cofactors, regulate the synthesis and secretion of growth hormone by increasing gene transcription. Similarly, as part of the feedback loop for hormone regulation and release, thyroid hormones affect transcription of TSH in the pituitary. In cardiac and skeletal muscle, thyroid hormones affect production of the muscle tissue myosin in a variety of ways, depending on the stage of life and specific muscle tissue affected. In addition, the hormones affect muscle contraction through genetic alteration of calcium uptake within the cell. Carbohydrate metabolism and formation of certain fats (lipogenesis) are affected through hormone-induced changes in gene transcription in liver cells.

Interleukin 6 Receptor

Region following the C2 set domain has homology with the extracellular portion of IL-2 receptor (3 chain, IL-3 receptor, IL-4 receptor, IL-7 receptor, growth hormone receptor, and erythropoietin receptor (a cytokine receptor family having four cysteines and the motif Trp-Ser-X-Trp-Ser). The intracytoplasmic portion of IL-6 reccptor is short and has no tyrosine kinase domain, unlike certain other growth factor receptors, and shows no homology with other known functional proteins. Thus it indicates that transduction of the IL-6 signal could be mediated through another molecule associated with the IL-6 receptor.

Pregnancy and lactation

Marked changes occur in the breast during pregnancy under the influence of a variety of hormones (e.g. oestrogens, progestogens, prolactin, insulin, growth hormone and chori-onic gonadotrophins). There is an increase in the number and size of lobules, and an increase in the number of acini within each lobule. During the third trimester, secretory vacuoles of lipid material appear in the epithelial cells, and is the precursor of milk production. Following birth, milk is secreted by the epithelial cells into the ductules, mainly under the influence of

Hormonal changes resulting from neuroleptic treatment

The secretion of growth hormone is under the control of the dopaminergic, noradrenergic, serotonergic and possibly other neurotransmitter systems. The acute apomorphine growth hormone challenge test has been used to assess D2 receptor function in untreated schizophrenics and in patients during neuroleptic treatment. Apomorphine-stimulated growth hormone secretion is reported to be higher in untreated schizophrenics and to be

Importance for Medicine and Industry

The ability to clone a gene is not only valuable for conducting biological research. Many important pharmaceutical drugs and industrial enzymes are produced from cloned genes. For example, insulin, clotting factors, human growth hormone, cytokines (cell growth stimulants), and several anticancer drugs in use are produced from cloned genes.

Duplications Of 17p112

Estimated prevalence of 1 20,000, is characterized by mental retardation, neurobehavioral abnormalities, sleep disorders, speech and motor delays, midface hypoplasia, short stature, and brachydactyly. 3 The same deletion is seen in 90 of patients. Only recently has it been recognized that a reciprocal duplication also exists. The dup(17)(p11.2p11.2) syndrome is characterized by borderline to mild mental retardation, behavioral problems, short stature, dental anomalies, normal facies, and lack of major organ malformations 4,5 This syndrome typifies a milder phenotype that was not recognized as a syndrome until connected to the microduplication.

Which of the Many Genes on Chromosome 21 Are Responsible for DS

The summary of molecular studies seen in the partial trisomy panel (Fig. 20.1) along with clinical data collected (Korenberg et al., 1994) provide the basis for a DS phenotypic map. By phenotype we mean any feature or measurable parameter, including neurocognitive, neuroanatomic, clinical, physical, cellular, and physiological features. The purpose of constructing a phenotypic map is to define molecularly the chromosomal regions and ultimately the genes, which are responsible for the variation in particular features. Although there are approximately 250 genes (see Chapter 18 by Patterson) known on this chromosome, overexpression of only a portion of them mapping to D21S267 at band 21q22.1 through the telomere can produce many of the characteristic features seen in persons with DS (Rahmani et al., 1989 McCormick et al., 1989 Korenberg et al., 1990 Korenberg et al., 1992). Nonetheless, it is known that the overexpression of genes on chromosome 21 outside this region is also associated...

The Total Artificial Heart

Constructing an artificial heart requires materials such as metals, ceramics, plastics, and polymers that are lightweight and durable. At the same time, these materials must be biologically inert. They must work synergistically with other body systems and not trigger attacks by the body's natural system of immune defenses that would lead to the disruption of the circulatory system and, ultimately, death. An artificial heart also requires sufficiently smooth surfaces so as not to disrupt blood flow through the heart or damage fragile blood cells. A TAH needs a power source that can maintain an efficient and steady stream of energy for long periods of time while being small enough to fit completely inside the body. Both the pump and the power source must be capable of responding to changes in position, temperature, and pressure associated with the needs of the person using the machine.

How Could the Perinatal Environment Influence Adult Metabolic Homeostasis

It is possible that systemic, tissue and or cellular adaptations to an adverse environment in the fetus might persist to later life and contribute to later metabolic disease. The neonatal environment may also interact with fetal adaptations and result in changes that further affect later disease risk. For example, if abundant nutrients are available to the neonate that was growth restricted in utero, the adaptations driving catch-up growth may lead to accumulation of lipid in adipose and other tissues,13'15'16 contributing to increased risk of diabetes.3 At the systemic level, the abundance of circulating hormones5 or activity of the sympathetic nervous system27 might be altered, possibly reflecting changes to the sensitivity of endocrine or nerve tissues to their regulatory signals. At a tissue level, the fetal environment might alter organ size

Disease Based Approaches

Probably the most common rejoinder to the problem of prevention is to distinquish the problems to which prevention efforts respond. Treatments are interventions that address the health problems created by diseases and disabilities (maladies in the helpful language of Clouser, Culver, and Gert). Enhancements, on the other hand, are interventions aimed at healthy systems and normal traits. Thus, prescribing biosynthetic growth hormone to rectify a diagnosable growth-hormone deficiency is legitimate treatment, while prescribing it for patients with normal growth-hormone levels would be an attempt at positive genetic engineering, or enhancement (Berger and Gert). Thus, to justify an

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. Patients with secondary adrenal insufficiency are better able to tolerate sodium deprivation without developing shock. Ihis is true because of intact aldosterone secretion. Hyponatremia, hyperkalemia, and azotemia are not prominent features of secondary failure. Hypoglycemia, however, may be more common in patients with hypopituitarism because of...

Alternative types of exercise yoga

'Eastern' exercises, such as yoga or Tai-chi, may be alternatives to aerobic or endurance training for people who are limited by severe shortness of breath. These exercises may bring about relaxation, calmness, balance, and may promote changes in the pattern of breathing, including slow and deep breath

Polymerase Chain Reaction Primer Design

The melting annealing temperature of a primer can be predicted from the nearest-neighbor model described above. The first requirement is that the primer pair must have closely similar annealing temperatures because extension of both strands occurs simultaneously under the same reaction conditions. The primers, being small and mobile, outcompete the complementary target strands and anneal forming a short double-stranded section with a long 5' single-strand overhang. The annealing temperature chosen for the PCR reaction is usually 5-10 C less than the melting temperature of the primer pair to promote stable hybridization between the primers (which typically exist in excess numbers) and the amplicon to obtain high yield in each cycle.

Neuroendocrine Regulation Of Immunity

Vasoactive intestinal peptide (VIP) and substance P have been investigated extensively for their actions on the immunologic functions and responses of lymphoid cells. These peptides and others, including mediators of the hypothalamic-pituitary-adrenal (HPA) axis such as growth hormone, prolactin, adrenocorticotropic hormone (ACTH), and various opioid peptides, have been shown to modulate immune responses in vitro. Indirectly, using antagonists and agonists of these mediators, in vivo modulation of immunity has also been observed. VIP is secreted by cells in the digestive system the functions of this peptide are vaso- and broncho-dilation, glycogenolysis, and stimulation of the secretion of other neuropeptide mediators such as prolactin, growth hormone and luteinizing hormone. VIP enhances or dampens lymphocyte-mediated

Clinical Management

The management of OI focuses on minimizing fractures and maximizing function in all aspects of the child's life. Until recently, the correction of deformities, intramedul-lary rodding of long bones, orthotic support, muscle strengthening, and mobility devices, such a wheelchairs, were the mainstays of treatment. 11 The recombinant human growth hormone has been used to augment growth and bone mass. The greatest potential currently resides in bisphosphonate therapy. Bisphosphonates as potent inhibitors of bone resorption have been shown to be highly effective in improving bone mass in children with severe forms of OI. 12 As a consequence, the fracture rate was reduced significantly and quality of life increased in all patients. However, in long-term therapy, bone turnover is suppressed to levels lower than those in healthy children, and the consequences of chronically low bone turnover in children with OI are unknown.

Minerals And Gene Expression

As noted in Table 7, several of the microminerals influence the expression of genes encoding one or more important proteins (7-21). Doubtless we will discover many more of these gene products that require one or more of the microminerals as part of the regulation of the transcription and translation of their cognate genes. Perhaps the mineral that has been studied the most is zinc because it is part of a group of DNA-binding proteins called transcription factors. In this role, zinc is bound by the histidine and cysteine residues of these binding proteins, giving these regions fingerlike projections that in turn bind to DNA at specific regions. These are illustrated in Figure 3. These proteins are called zinc finger proteins and the zinc-bound regions, zinc fingers. A number of nutrients, namely, vitamin A and vitamin D, and hormones, namely, steroids, insulinlike growth factor I, growth hormone, and others, have their effects on the expression of specific genes because they can bind...

The Mucopolysaccharidoses

Often, MPS disorder results in impairment of the skeletal system. Other organ systems that are impacted include the cardiovascular, respiratory, and nervous systems. Skeletal impairments include widened collarbone and ribs, progressive curvature of the lower spine, short stature, shortened neck, claw-like hands, joint contractures, enlarged head, flattened bridge of

Contemporary Echoes of a Eugenic Past The Genetic Screen

Colleges and the exorbitant pricing of the ova from supermodels, which are offered on a website. Given a choice, there is evidence that some people will try to add a bit of height to their offspring with a growth hormone. Each of these developments indicates a lingering of a eugenic past.

Endocrine Systems and Metabolism

As stated above, the pituitary gland is the hub of endocrine regulation. Important among the decline stimulation within the axis is that growth hormone (GH) secretion declines with increasing age, a condition termed 'somatopause.' The changes in the growth hormone insulin-like growth factor axis with aging produce changes in function, metabolism, and body composition analogous to the pathological growth hormone deficiency seen in younger adults. Another change with age is the efficiency with which physical activity stimulates the secretion of GH.

Detection Of Human Platelet Antigens

Quence at the site of allelic variation, a PCR product will be generated. However, when the 3' nucleotide of the primer is mismatched, the amplification of the template will not occur or will proceed with very low efficiency. For the detection of each HPA allele, two sets of primers are designed, each set containing an allele-specific primer and a common primer. After gel electrophoresis of the PCR product, DNA is stained and analyzed under UV light. The HPA genotype is then determined by the absence or presence of a DNA fragment. As an internal control for the success of the PCR reaction, an additional pair of primers for the amplification of the human growth hormone gene or another gene is usually added to each reaction.

Late Gestational Glucocorticoids and Programming of Blood Pressure

Administration of dexamethasone to rats throughout the final third of gestation results in offspring that are growth restricted in utero, hypertensive as adults, and have abnormal HPA function.28 Betamethasone treatment of pregnant rats throughout this same period reduced birth weight but did not alter postnatal blood pressure.37 There are numerous potential explanations for the discrepant findings from these two studies.37 Other experiments using rats, in which dexamethasone treatment was restricted to shorter periods during the final third of pregnancy, have demonstrated an association between postnatal hypertension and reduced nephron endowment but only when dexamethasone treatment occurred between 70-85 of gestation, and not at earlier or later times.38 As mentioned above, repeated maternal dexamethasone treatments during late pregnancy (which do not significandy alter birthweight) result in hypertension in mature, but not younger adult, male offspring31'33 but the underlying...

Physiological Somatostatin Receptor Ligands

Somatostatin (SS), originally called somatotropin-release inhibiting factor or SRIF, was discovered accidentally over 30 years ago while investigators were hunting for the brain peptide responsible for stimulating the release of growth hormone, or somatotropin. Surprisingly, they found that extracts of the hypothalamus, a specialized brain region that regulates pituitary hormone secretion, inhibited rather than stimulated the secretion of growth hormone. Using this inhibition as an assay, R. Guillemin, A. Schally, and their co-workers purified the active factor from hypothalamic extracts and identified the 14-amino-acid form of somatostatin, a discovery that contributed to their receiving the Nobel Prize in 1977 for studies of hormone production in the brain.

The Plan Of The Revised Edition

Much water has passed under the bridge with respect to debate over biotechnology since the first edition appeared. I have tried to update discussion of the debate to reflect more recent controversies in a few cases, but I have not tried to do so in anything like the detail (which was not intended to be exhaustive, in any case) in the original edition of the book. While the first edition made some attempt to document the popular, regulatory and intellectual debate over food biotechnology, any extended attempt to update this aspect of the original book would have resulted in a totally different book. In fact, the revised edition has eliminated a number of pages documenting the debate over biotechnology. In some cases, especially environmental risks, the debate has progressed to the point that some of the sources (dating back to the 1980s) discussed in the original edition no longer seem relevant. When the original manuscript was written, the most significant debate over food...

The Host Tumor Relationship Endocrine Factors and Stromal Reaction

Normal homeostasis is controlled in the organism by a delicate balance of multiple intercellular regulatory molecules generally known as hormones. This is not to say that small molecules such as glucose, nonesterified fatty acids, amino acids, and other small molecule substrates are not important in the homeostasis of the organism. However, generally speaking, the functional, trophic (replicative), and tissue-specific controlling factors that maintain organismal ho-meostasis are hormones. Hormones may be polypeptide in character, such as growth hormone and insulin, or of low molecular weight, such as prostaglandins and steroid hormones. Some groups of hormones have distinctive designations dependent on their function, such as cytokines (Chapter 19), interleukins (Chapter 19), growth factors (Chapter 16), and others. Still, in the general sense, these chemicals produced by specific cells and acting in an autocrine, paracrine, or endocrine manner may be considered as hormones. In...

Prolonged Responses to Cytokines andor Hormones

Hormones such as growth hormone have been shown to reduce phagocytic and metabolic function in neutrophils. This is the result of reduced TNF production (35). Glucocorticoids have also been shown to block PAF-induced downregulation of CD62L and upregulation of CD11 CD18 on neutrophils. This suggests that ligation of glucocorticoid receptors has an anti-inflammatory effect on cells by the inhibition of leukocyte accumulation at sites of tissue injury (36).

Mechanisms of Altered Hormone Gene Expression in Endocrine Neoplasms

In 1990 Lyons and associates (Lyons et al., 1990) described a putative cellular oncogene termed gsp. The wild-type protooncogene of gsp is the a-subunit of the G protein involved in the response of pituitary cells to growth hormone-releasing hormone (GHRH). A diagram of the effect of the mutations that have been found in this proto-oncogene is seen in Figure 18.7. The amino acid substitutions noted result in constitutive activation of adenyl cyclase (AC) and subsequent cyclic AMP formation, which, in turn, activates a signal transduction pathway leading to both hyperplasia and hyperfunction (cf. Spada et al., 1994, 1998).

Thalamic Projections To Subcortical Regions And Somatosensory Cortex

Information from different parts of the body project to different parts of each cortical strip. Thus, each strip contains an orderly representation of the body called a homunculus (Latin for little man'') that is derived from the location of the receptive fields of the input neurons. The homunculus is not true to scale, however, and certain areas, such as lips and fingertips, are grossly overrepresented. The high density of sensory receptors in these locations requires proportionally

Biologically Active Peptides

Biologically Active Peptides Found in Foods. Foods of animal origin, especially milk, contain large numbers of peptides belonging to the first group. Today, many biologically active peptides such as epidermal growth factor, nerve growth factor, insulin, prolactin, somatoatatin, thyroid-releasing hormone, thyroid-stimulating hormone, growth hormone-releasing factor, luteinizing hormone-releasing hormone, adrenocorticotropic hormone, erythropoietin, bombesinlike peptides, calcitonin, and delta-sleep-inducing peptide are detected in milk by sensitive radioimmunoassay. In neonates, the proteolytic activity in the gastrointestinal tract is usually low and the intestine shows considerable permeability to large peptides. Therefore, these biologically active peptides found in milk might have a physiological function in the development of the gastrointestinal tract and other organs. In fact, epidermal growth factor given orally to newborn rats has been shown to increase the weight of the...

Protein Turnover and Regulation

The term protein turnover reflects the balance of protein degradation and resynthesis. From a quantitative standpoint, by far the greatest influence on amino acid turnover and metabolism is this turnover cycle in which proteins are continuously degraded and resynthesized. Co-regulation of synthetic and degradative arms of the cycle is crucial to maintaining cellular viability, to regulation of growth and cellular protein mass, and to control of enzyme levels. At least 20 of basal energy expenditure is used in maintaining whole-body protein synthesis. Body protein mass and rates of protein gain or loss in a cell are entirely dependent on the balance of these mechanistically distinct processes, i.e., the relative rates, of protein synthesis and degradation. Although both processes are influenced by protein and energy nutritional status and by the same hormones (e.g., insulin, growth factors, growth hormone, and glucocorticoids), direction and magnitude of a response of either process...

Functional energetic epitopes and crossreactivity

Lementarity contributed by the surrounding contact area. The concept offered a resolution of an apparent paradox on the one hand, a multitude of side-chain-side-chain interactions at the interface ( 16 side-chains in the antibody as well as in the antigen) and, on the other, the experimentally derived size of the binding site no larger than 4-6 amino acids. A number of experimental data consistent with the hypothesis of an energetic epitope have accumulated, including those obtained on antibodies to the human growth hormone, human placental lactogen, the repressor, hen egg-white lysozyme, N9 neuraminidase, cytochrome c and cyclosporine. The concept of a 'functional (energetic)' epitope has also given us an additional perspective on cross-reactivity (cf, for example, the NC41 and NC10 neuraminidase epitopes, Figure 5) and antigenicity. Antigenic analysis of the human growth hormone, the most extensive study of this kind currently at hand, showed that the functional epitopes correlated...

Regulation of Appetite

Ghrelin is synthesized as a preprohormone which is cleaved by proteolysis to a 28 amino acid peptide (a 27 amino acid variant also exists). The serine residue at position 3 must be substituted with octanoic acid for activity. Ghrelin released into the circulation has several actions, stimulation of the release of growth hormone from the anterior pituitary, increasing the hunger signal by binding to receptors on the hypothalmic feeding centers and promoting gastric emptying to clear the stomach for the approaching meal. The effects of ghrelin are counter balanced by the hormones released in response to the feed state, somatostatin from the stomach D cells and GLP-1 and peptide YY from the L cells of the samll intestine.

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.

Phenotype and Genotype

An organism's observable characteristics, such as height, hair texture, skin color, or ear shape, are known as the phenotype of that organism. The phenotype is determined partly by the environment and partly by the set of genes that the organism inherited from its parents. Adult height, for instance, is due partly to nutrition (an environmental influence), and partly to a set of genes governing things such as rates of bone growth, sensitivity to specific hormones, and the like. Phenotype includes not only large-scale characteristics such as height, but every expressed trait, including the types and amounts of all the proteins produced in each cell in the body.

Growthrelated Transgenes

Early transgenic farm animal research was inspired by the dramatic growth of transgenic mice that expressed a growth hormone (GH) transgene. 1 A number of transgenic pigs and sheep were subsequently produced with human, bovine, rat, porcine, or ovine GH under the control of several gene promoters. 2 Although pigs expressing GH transgenes grew faster, utilized feed more efficiently, and were much leaner than their nontrans-genic siblings, they were not larger and exhibited several notable health problems, which included lameness, susceptibility to stress, gastric ulcers, and reproductive prob-lems. 2 The GH transgenic lambs did not grow faster or utilize feed more efficiently than control lambs, but they were much leaner and had serious health problems. 2

DNA Vaccination Techniques

This innovation in vaccination strategy was discovered some years ago, but the active development of this technology only began after Stephen Johnston's group at the University of Texas Southwestern Medical Center demonstrated that plasmid DNA can induce the formation of antibodies against an encoded protein in 1992. Johnston's group was able to show that when mice are innoculated with plasmid DNA encoding human growth hormone, the mice produce antibodies against the hormone.

Socialization of Boys and Girls

As in many societies, the first question about a new baby in Zapotec communities is whether is it a little man or a little woman. Preference is usually expressed for a little man. Thus, from the instant a child is born, they are gendered in conversation and in the way they are treated.

Growth and Development of Children

Growth Zinc plays an important role in child growth. Several mechanisms may be involved, including the role of zinc in the transcription and translation of genetic material and, perhaps more importantly, the regulatory role of zinc in the primary endocrine system, which controls growth (i.e., the growth hormone-somatomedin axis). Specifically, zinc status is associated with the concentration of circulating insulin-like growth factor-1, the principal growth factor that controls early childhood growth. Among populations where growth retardation occurs, both height and weight gain have improved following supplemental zinc. Stimulation of linear growth appears to be the primary response, while the increase in body weight likely reflects the synthesis of lean tissue such as bone, cartilage, and muscle associated with linear growth. This is evident because, in general, weight does not increase independently of increased height in response to supplemental zinc.

Influence of Fetal Endocrine and Autocrine Paracrine Acting Growth Factors on Fetal Growth

Growth hormone, which classically acts as the major regulator of postnatal growth, has no demonstrable influence on fetal growth. Fetal insulin does regulate fetal growth, although the complete absence of insulin does not abolish fetal growth. In sheep, for example, fetal pancreatectomy in late gestation limits fetal growth rate only by 20-30 , and pancreatic agenesis in humans produces IUGR fetuses who are 30-50 less than normal weight near term. Insulin infusions into the fetus and excessive fetal insulin secretion enhance fetal glucose utilization and produce increased adiposity, but only a 10-15 increase in fetal nonfat growth. Such hyperinsulinemic conditions also limit protein breakdown, which leads to increased protein accretion, although by limiting protein breakdown, as well as by enhancing amino acid synthesis into proteins, insulin actually decreases plasma concentrations of amino acids, thereby limiting protein synthesis at the same time. Therefore, it is not clear how...

The Interrelationship Between Psychopharmacology and Psychoneuroimmunology

Fever and sleep are important events which assist recovery following an infection by helping to destroy heat-sensitive foreign microorganisms. One of the key promoters of sleep and fever following an infection is IL-1. This cytokine can penetrate some areas of the blood-brain barrier and raise the temperature ''set point'' in the hypothalamus thereby producing a fever. Similarly IL-1 promotes slow-wave sleep and thereby facilitates tissue repair due to the secretion of growth hormone during that sleep phase. In addition to facilitating tissue repair, growth hormone can also boost the immune system. Whereas the precise mechanism whereby the cytokines T cells are particularly sensitive to the inhibitory effects of the glucocorticoids. In particular, the nascent T cells, which represent about 90 of all T cells in the thymus gland, are very sensitive to the inhibitory effects of these steroids high steroid concentrations can also prematurely induce the migration of T cells from the thymus...

Metabolic and Nutritional Disorders

Excessive production of growth hormone in the adult results in acromegaly, which has been diagnosed in ancient skulls and on some depictions on coins. It has been suggested that the skull of the Pharaoh Akhenaten showed acromegalic changes, perhaps as a manifestation of a multiple endocrine adenopathy syndrome.

Nutritional Assessment in Rheumatoid Arthritis

Healthy persons of the same weight, age, race, gender, and height, patients with RA have lower body cell mass (especially muscle mass) and increased fat mass. This condition has been termed 'rheumatoid cachexia,' and it occurs despite adequate and even excessive dietary intake. This cachexia is generally seen in the presence of hypermetabolism (elevated resting energy expenditure) and hypercatabolism (elevated protein breakdown), along with reduced physical activity. These metabolic abnormalities are linked to increased production of the catabolic cyto-kines IL-1 3 and TNF-a. The problems are further exacerbated by reduced physical activity, which reduces the anabolic stimulus to muscle, and disordered growth hormone kinetics. In addition, patients with RA have lower concentrations of serum albumin and other markers of visceral protein status, and often have anemia of chronic disease with disordered iron metabolism.

Physiology of Lactation

Numerous metabolic changes must occur as mammals make the transition into lactation. Examples of this adaptation include mobilization of fatty acids, Ca, and amino acids from body stores to meet the needs of mammary cells, and an increase in hepatic gluconeo-genesis. Typically, these changes depend on alterations in hormonal secretory rate, changes in receptor numbers on target cells, or modified receptor signaling mechanisms to change the responsiveness of tissues to normal signals. Examples of this in postpartum animals include the increased ability of adipose tissue to release fatty acids in response to stimulation by epi-nephrine, the decrease in rate of lipogenesis in adipose tissue in response to insulin, and an increase in the capacity of the liver to produce glucose in response to growth hormone and epinephrine. The reader is referred to more thorough reviews by Bauman and Currie, 1 and Bauman and Vernon 2 in which the concept of homeorhesis, or orchestrating metabolism in the...

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...

Aspects of the biochemical basis of depression

Other studies have shown that the elevation of growth hormone in the plasma following the administration of the alpha-2 adrenoceptor agonist clonidine is diminished in depressed patients, which suggests that central postsynaptic alpha-2 adrenoceptors are also subfunctional in such patients. This is perhaps the most consistent finding to have emerged in studies of the hypothalamic-pituitary axis in depression. As the clonidine response does not return to normal after effective antidepressant treatment, this is possibly a trait marker of depression. It should be emphasized that the reduced growth hormone response to clonidine cannot be accounted for by drug treatment, age or gender of the patient, which supports the view that the noradrenergic system is dysregulated in depression. Lastly, determination of the urine or plasma concentrations of MHPG (an indicator of central noradrenergic activity) suggests that central noradrenergic function is suboptimal in depression. Taken together,...

Brain Systems Controlling Eating

Norepinephrine, endorphins, galanin, and neuropeptide Y are transmitters that act in the PVN to facilitate food intake (13). Of special interest here is the finding that the stimulatory effects of norepinephrine in the PVN appear to be specific to carbohydrate intake (13). Elsewhere, growth hormone-releasing factor in the medial preoptic area of the hypothalamus stimulates eating (14). Neurotransmitter signals involved in inhibiting eating include dopamine and norepinephrine in the perifornical region of the hypothalamus as well as serotonin in the PVN (13). Interestingly, serotonin's inhibitory effect, like norepinephrine's stimulatory effect, is carbohydrate selective (13).

The Diencephalon 1 The Thalamus

Circuitry Motor Cortex

The hypothalamus (Fig. 13) lies at the heart of the limbic system. With dual outputs, it plays key roles in short-term and long-range homeostasis. Its neural output is effected by descending tracts in the core of the neuraxis and its endocrine output by pituitary hormones. It regulates vegetative functions control of body temperature, caloric input, water-osmolar balance, and sleep-wakefulness. It selects and integrates autonomic responses. It controls the release of adeno-hypophyseal and neurohypophyseal hormones that exert far-ranging and, in some cases (growth hormone), enduring effects on the body.

Pharmacological Management of Undernutrition

Growth hormone Several agents previously touted as effective orexi-genic agents, such as human growth hormone, have fallen out of favor. The administration of human growth hormone to healthy older adults has been shown to increase muscle bulk. However, significant side effects such as carpal tunnel syndrome, gynecomastia and hypoglycemia were noted furthermore, the increase in muscle bulk failed to produce a parallel increase in muscle strength. Inadequate data regarding the safety and efficacy of growth hormone administration precludes routine clinical use. Similarly, the role of insulin-like growth factor (IGF-I) in the management of undernutrition is questionable. Although the data suggest that exo-genously administered IGF-I may enhance nitrogen retention, gluconeogenesis, and maintenance of normal gastrointestinal function, evidence-based outcome studies are lacking.

Interferon 7 Receptor

Ifn Myasthenia

The three-dimensional structure of homodimeric IFN7 complexed with two molecules of the ligand-binding extracellular domain of ifngr-1 (Figure 1) shows extensive contact between the ligand and receptor, including residues from several loops of each FBN III domain, in a manner reminiscent of the human growth hormone complex with its receptor. However, the membrane-proximal FBN III sub-domains of the two bound ifngr-1 receptors do not

Mammary Glands Hormonal Regulation

Studies of rodents that utilized a combination of endocrine gland removal, followed by gland or hormone replacement were foundation experiments to demonstrate hormonal regulation of mammary devel-opment. 4'5 These studies showed very clearly that removal of the ovaries or the pituitary glands had very significant and negative effects on mammary gland development. It is now realized that both estrogen and progesterone from the ovaries, as well as prolactin and growth hormone from the anterior pituitary gland, are essential for normal mammogenesis in most mammals. Placental lactogen, a member of the growth hormone prolactin family, can at least partially replace prolactin and growth hormone in their ability to induce mammary proliferation, but this hormone is not secreted from the placenta of all mammals. 6,7 It is likely that the combination of circulating hormones delivered to the mammary glands from blood, in turn, stimulates the local production of mammary growth factors, such as...

Molecular Biology Animal

A number of genes associated with growth and productivity traits have been identified by genome-mapping approaches. 1,9 The availability of these genes provides an excellent opportunity for marker-assisted breeding 9 and genetic manipulation by transgenesis 6 to produce new breeds with desired traits. Generation of transgenic animals bearing the desired genes or gene alleles is the most straightforward approach. For example, transgenic pigs and sheep overexpressing growth hormone or growth hormone-releasing factor normally grow faster and utilize feed more efficiently than nontransgenic littermates. 6,10 Transgenesis efforts to alter milk composition, wool formation, and meat quality are currently ongoing. With the advances of new molecular techniques, particularly through genome sequencing and DNA microarray, additional genes will be identified, providing more and better targets for breeding and genetic manipulation.

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...

Growth Factor Signaling

Production of IGF occurs both systemically and locally. Growth hormone regulates the levels of IGF generated by the liver, the major site of IGF production. Increased serum levels of IGF are critical for the proper maintenance of terminal end bud structures in the mammary gland. The role of IGF in prevention of or susceptibility to breast cancer stems largely from correlative evidence in human studies and direct evidence in rodent studies. Epidemiological studies analyzing possible roles for IGF in breast cancer have indicated that premenopausal women with serum IGF levels in the highest quartile have an increased incidence of breast cancer. Conversely, well established protective therapies such as tamoxifen, fenretinide, and caloric restriction are associated with a decrease in IGF serum levels. However, the most convincing evidence that high IGF levels and signaling may be related to breast cancer is obtained from genetically defined rodent models with alterations in the IGF...

Neuroendocrine pathways to the immune system

In addition to corticosteroid effects, a number of the nonsteroidal hormones, produced by other neuroendocrine organs in response to hypothalamic-pituitary messages, also influence immune responses for example, sex hormones diminish in vivo responses, while growth hormone, thyroxine and insulin elevate responses under certain conditions. Numerous neuropeptides and neurotransmitters, which exert multiple functions as intercellular messengers within the nervous system, may also modify functional properties of cells of the immune system (Figure 2). For example, in addition to the elevation of CRH, corticosteroids and the catecholamines with stress, levels of 3-endorphin, which is derived along with ACTH from cleavage of the pro-opiomelano-cortin polyprotein, are also elevated, as are levels of several other opiates. Opiates function to alleviate pain during a fight-or-flight encounter but also inhibit immune responsiveness. In contrast, two anterior pituitary hormones, growth hormone and...

Hormonal Interactions During Exercise

FIGURE 9 Concentrations of glucose in the plasma of normal subjects (Control) and patients suffering from isolated deficiency of GH (shown in blue) while eating normally and while fasting. Some GH-deficient patients were untreated while others were given 5 mg of human GH per day (treated). Fasting began after collection of blood on day 2. From Merimee, TJ, Felig, P, Marliss, E, Fineberg, SE, Cahill, GF Jr. (1971). Glucose and lipid homeostasis in absence of human growth hormone. J. Clin. Invest. 50 574-582. With permission.

Inborn Errors of Fructose Metabolism

The aldolase A, B, and C enzymes catalyze the reversible conversion of fructose-1-diphosphate into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate, and deficiencies in the A and B enzymes have been identified. Aldolase A is expressed in embryonic tissues and adult muscle. Possibly owing to the importance of this enzyme in fetal glycolysis, its deficiency results in mental retardation, short stature, hemolytic anemia, and abnormal facial appearance. There is no known treatment for aldolase A deficiency. Aldolase B is expressed in liver, kidney, and intestine, and a deficiency of this enzyme is more common and can be exhibited at first exposure to fructose during infancy or can have its onset in adulthood. Upon ingestion of fructose-containing foods, vomiting and failure to thrive are apparent. Hypoglycemia (in some cases severe), increased blood uric acid, and liver dysfunction also occur. Fortunately, this disorder can be treated effectively by completely eliminating...

Hepatic Glucose Metabolism

Cancer patients, the etiology for the elevated rate of fasting hepatic glucose production is not known. Early studies tested whether excessive growth hormone (GH) release in cancer patients might be responsible. However, there was no direct correlation between GH secretion pattern and hepatic glucose production. Furthermore, the administration of GH to cancer patients for a 3-day period failed to increase the rate of glucose production. Koea and Shaw suggested that the rate is related to the bulk of the tumor, and others have suggested it is related to cytokines or other factors. Earlier studies on normal volunteers demonstrated that the loss of the first-phase insulin response causes a delay in the normal inhibition of glucose production. Although the latter effect may explain postprandial hyperglycemia, it is an unlikely explanation for fasting hepatic glucose production.

Inflammatory Lesions 1 Infections

CJD occurs in sporadic, inherited (several mutations) and iatrogenic forms due to transplants of cornea or dura, insufficiently sterilized neurosurgical instruments, and growth hormone extracted from human hypophyses. The clinical course of all three forms is comparable progressive dementia often accompanied by myoclonus, visual, cerebellar, or motoric disturbances and finally an akinetic mutism and decerebration. The electroencephalogram shows typical periodic complexes of sharp waves in an underlying decelerated background activity. Since

Applications Of Genetic Engineering In Food Science

Animal embryo transfer technology and production of transgenic animals by microinjection of foreign genes into eggs (transgenesis) to increase animal productivity and product value has become possible. Biotechnologists have produced transgenic sheep (Dolly) and injected about 1 million copies of rat growth hormone gene into fish eggs to show about 5 of fish hatched were transgenic (with rat growth hormone). In sheep, goats, pigs, and cattle, presence of growth hormone produces leaner meat. In Edinburgh, Scotland, researchers have had success in creating transgenic sheep that produced milk with human anti-

Characterization of Protein Ligand Binding Sites

Other approaches are also available to determine the arrangements of residues in a binding site. One involves a laborious process of systematic derivatization and mutation of residues of a peptide or protein ligand, in order to determine the effects of these changes on a biological response, which then provide spatial information about the binding surface and the characteristics of that surface. One version of this process that is widely used for detecting and analyzing binding interfaces is that of alanine scanning mutagenesis 40, 41, 42, 43 . This technique, which was first applied to the human growth hormone and its receptor, consists of the systematic mutation of surface residues to Ala, with concomitant measurement of the effect on the binding constant for the protein-ligand interaction 3 . The seminal work on the human growth hormone receptor complex showed that a few hydrophobic interactions contribute a significant portion of the binding affinity in this largely hydrophilic...

Regulation Of Metabolism During Feeding And Fasting

When either growth hormone or glucocorticoids are present in excess for prolonged periods, diabetes mellitus often results. Approximately 30 of patients suffering from excess GH (acromegaly) and a similar percentage of persons suffering from Cushing's disease (excess gluco-corticoids) experience diabetes mellitus as a complication of their disease. Most of the others have some decrease in their ability to Growth hormone (I) intestinal hormones, especially glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), which are potent secretagogues for insulin. Finally, the beta cells respond directly to increased glucose and amino acids in arterial blood (see Chapter 41). During the postprandial period the concentration of insulin in peripheral blood may rise from a resting value of about 10 mUnits mL to perhaps as much as 50 mUnits mL. Glucagon secretion may also increase at this time in response to amino acids in arterial blood. Dietary amino acids may also...

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...

Iodine Deficiency and Excess Iodine Deficiency

Myxoedematous cretinism presents as disturbances of growth and development including short stature, coarse facial features, retarded sexual development, mental retardation, and other signs of hypothyroid-ism. It appears likely that severe deficiency resulting in decreased maternal T4 may be responsible for the impaired neurological development of the fetus occurring early in pregnancy. The effect of deficiency on the fetus after 20 weeks' gestation may result in hyperstimulation of the developing fetal thyroid, with the extreme manifestation being thyroid failure causing myxoedematous cretinism. Other factors may affect thyroid hormone metabolism. Selenium deficiency, when present with iodine deficiency, may alter the clinical manifestations. Selenium deficiency decreases the activity of the enzyme, glutathione peroxidase (GPX), which, along with thyroid hormone synthesis, reduces hydrogen peroxide (H2O2). Combined with iodine deficiency and reduced hormone synthesis, it has been...

Changes in Calcium Metabolism during the Life Span

The efficiency of calcium absorption is highest during infancy (approximately 60 ), and the amount absorbed from breast milk does not appear to be affected by calcium consumed in solid foods. During the growth spurt of adolescence, calcium retention and accretion increase to peak at approximately 200-300 mg per day in girls and boys, respectively. It involves the action of growth hormone, IGF-1, and sex steroids. The onset of menstruation in girls is associated with a rapid decline in bone formation and resorption. Intestinal calcium absorption is predictably more efficient during the growth spurt and also decreases subsequently. Importantly, it is thought that calcium intakes during the period of growth can affect the peak bone mass achieved and therefore influence the amount of bone mineral remaining when osteoporosis begins in later life. Bone mass may continue to accumulate up to approximately age 30 years, although the amount gained is relatively small after age 18 years.

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

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