Hormones

Hormones are classified into three groups based on chemical structure:

• Amino acid derivatives: derivatives of either tyrosine (e.g., catecholamines and thyroid hormones) or tryptophan (e.g., melatonin).

• Peptide hormones: glycoproteins, short peptides, or small proteins (under 200 amino acids). Examples include growth hormone and insulin.

• Lipid derivatives: either eicosanoids (derivatives of arachidonic acid), such as prostaglandins, or steroids (derivatives of cholesterol), such as hydrocortisone.

Tables 9.1, 9.2, and 9.3 summarize most of the hormones and their functions. Although others are known, some are still poorly understood.

TABLE 9.1 Peptide Hormones

Gland

Hormone

Target and Function

Hypothalamus

Anterior pituitary

Antidiuretic hormone, or vasopressin (ADH)

Oxytocin

Releasing and inhibiting hormones Thyroid-stimulating hormone (TSH)

Follicle-stimulating hormone (FSH)

Stored in posterior pituitary; when released, it increases water resorption by the kidneys; it is inhibited by alcohol.

Stored in posterior pituitary; when released, stimulates milk ejection and uterine contractions in females, ductus deferens and prostate in males; secreted by uterus and fetus; released in orgasm in both sexes.

Controls the release of hormones of the anterior pituitary, a different one for each.

Stimulates synthesis and secretion of thyroid hormones; stimulated by hypothalamic thyrotropin-releasing hormone (TRH).

Females: stimulates follicle maturation and estrogen synthesis; males: stimulates production of sperm; stimulated by hypothalamic gonadotropin-releasing hormone (GnRH).

TABLE 9.1 (Continued )

Gland

Hormone

Target and Function

Intermediate pituitary Parathyroid

C cells of the thyroid Heart

Thymus Pancreas

Leuteinizing hormone (LH)

Prolactin (PL)

Growth hormone

(somatotropin, GH) Adrenocorticotropic hormone (ACTH) Melanocyte-stimulating hormone (MSH) Parathyroid hormone (PTH)

Calcitonin (CT)

Atrial natriuretic peptide (ANP)

Thymosins Insulin

Glucagon

Digestive tract Gastrin

Cholecystokinin Kidneys Erythropoietin (EPO)

Females: stimulates ovulation, formation of corpus luteum, and synthesis of estrogen and progesterone; males: stimulates synthesis of testosterone; stimulated by hypothalamic GnRH.

Stimulates growth of mammary gland and synthesis of milk.

Stimulates growth of all cells, but the cells of the bone and cartilage are especially sensitive.

Stimulates production of steroids in adrenal cortex, part of the response to stress.

Increases melanin synthesis in epidermis (not active in adults except pregnant women).

Increases calcium in circulation by stimulating bones to release it, enhances digestive uptake, and inhibits kidney removal.

Opposite effect of PTH, decreases calcium in blood.

Release stimulated by stretch receptors in cardiac muscle; it promotes loss of sodium and water in kidney, supresses thirst and water-conserving hormones.

A blend of hormones that induce T-cell differentiation in the immune system.

Stimulates the uptake and use of glucose by cells throughout the body, the production of glycogen by the liver and skeletal muscles, and the formation of fats by adipose tissue. The effect of insulin on glucose uptake by cells is indirect; it stimulates an increase in the production of membrane proteins that transport glucose through the membrane by facilitated diffusion.

Released when blood glucose is low: stimulates cells throughout the body to release glucose, the liver to break down glycogen into glucose, and the breakdown of fats by adipose tissue.

Stimulates hydrochloric acid secretion by the stomach.

Stimulates the exocrine cells of the pancreas to secrete digestive enzymes.

Produced in response to low oxygen in the kidney; stimulates red blood cell production by bone

Liver

Renin (actually an enzyme) Angiotensinogen (a plasma protein)

Converts angiotensinogen to angiotensin I in the blood.

After conversion by renin in the blood and other enzymes in the lungs, it becomes angiotensin II, which stimulates thirst and production of aldosterone and ADH, causing sodium and water retention. This is part of the response to low blood volume.

TABLE 9.2 Amino-Acid-Derived Hormones

Gland

Hormone

Target and Function

Pineal gland

Melatonin

Thyroid

Thyroxine (T4) and triiodothyronine (T3)

Pineal gland receives stimuli from visual neurons that reduce melatonin production during the day and increase it at night.-Thought to be involved in circadian (daily) rhythms of the body. Increases during dark winters thought to cause seasonal affective disorder (SAD), a disorder that affects mood, sleeping, and eating. Synthesis of thyroxine and triiodothyronine requires iodide. Synthesis and release is stimulated by hypothalamic regulatory enzymes. Produces a rapid, short-term increase in metabolic rate by binding to mitochondria, and by activated genes that code for glycolysis enzymes.

Catecholamines

Adrenal medulla

Epinephrine (adrenaline) and norepinephrine

Hypothalamus

Dopamine

Epinephrine makes up about 75% of the release of the adrenal medulla; the rest is norepinephrine. Release is stimulated by the sympathetic division of the autonomic nervous system as part of the fight or flight response. Causes skeletal muscles to break down glycogen to glucose as a ready source of energy, adipose tissue to break fats down to fatty acids for other tissues to use, the liver to break down glycogen for use by the neurons that cannot use fatty acids.

Controls release of prolactin.

The molecules that the hormones interact with are called receptors. The effect of a hormone depends not only on how much hormone is in circulation but how many receptors are present and on which cells. This is an important aspect of hormone control. Different tissues may vary in their numbers of receptors for a particular hormone. This enables the action of hormones to be selective. Change in receptors is also a mechanism for the control of hormone response. For example, thyroid hormone stimulates adipose cells to produce receptors for epinephrine, increasing their sensitivity to epinephrine's causing the release of fatty acids. The interaction of a hormone with a cell-surface receptor ultimately results in the activation or inhibition of an enzyme within the cell. Many drugs are designed to either stimulate or interfere with receptors.

The lipid hormones enter the cell and complex with the DNA in the nucleus. They then either stimulate or inhibit gene expression, and ultimately, the cell function. For example, testosterone stimulates production of structural proteins in skeletal muscles, increasing muscle size and strength. Thyroid hormones, in addition to complexing with DNA, may bind to mitochondria, causing an increase in ATP production.

Hormones are also controlled by changes in the composition of intercellular fluids, by other hormones, or by neural stimulation. The hypothalamus and the adrenal medulla are

TABLE 9.3 Lipid-Derived Hormones

Gland

Hormone

Target and Function

Many tissues

Eicosanoids

Leukotrienes Released by white blood cells, they coordinate tissue responses to injury and disease.

Prostaglandins Generated by most tissues of the body, converted by platelets in the blood to thromboxanes.

Thromboxanes Causes platelets to aggregate and the smooth muscles of the blood vessel walls to contract.

Steroids

Reproductive organs

Follicles of ovaries Corpus luteum of ovaries

Adrenal cortex

Kidneys

Androgens (testosterone and others) Testosterone

Estrogens (e.g., estradiol) Progestins (e.g., progesterone)

Several dozen hormones, e.g.: Aldosterone

Glucocorticoids (e.g., cortisol, hydrocortisone, corticosterone)

Androgens Calcitriol

Produced by testes, it promotes sperm growth, stimulates overall growth, especially of the skeletal muscles, and produces aggressive behavior.

Stimulates maturation of egg cells and growth of the lining of the uterus.

Prepares uterus for embryo, stimulates movement of egg or embryo, stimulates enlargement of mammary glands.

In response to drop in blood sodium, volume, or pressure, stimulates retention of sodium by kidneys, sweat glands, salivary glands, and pancreas; increases sensitivity of salt-sensing taste buds in tongue; also stimulated by angiotensin II.

Accelerates glucose synthesis and glycogen formation, especially in the liver; stimulates tissues to use fatty acids for energy instead of glucose, reduce inflammation by inhibiting white blood cells and mast cells. Cortisol inhibits its own production by a negative feedback loop involving the hypothalamus and ACTH.

The ''sex'' hormones, including testosterone. Some are converted to estrogen.

One of the D vitamins, released in response to PTH. Stimulates absorption of calcium and phosphate by the digestive tract, stimulates differentiation and behavior of bone cells, and inhibits PTH production.

stimulated directly by nervous activity. The hypothalamus controls the release of many hormones from the anterior pituitary, which in turn affects numerous other hormones and tissues. It also controls the release of vasopressin and oxytocin, which it produces, but which are stored in the posterior pituitary. This arrangement makes it possible to have a rapid response for urgent needs such as blood pressure control.

Hormones, endocrine organs, and the nervous system interact in complex ways. Figure 9.6 shows one case that illustrates this complexity schematically. That this system is much more complex than portrayed in the figure is apparent when one considers that each box represents a complex stimulus-response process in itself.

One of the most common diseases of the endocrine system is diabetes mellitus, which results in unstable blood glucose levels. Diabetes is the result of either inadequate insulin production, production of abnormal insulin, or production of defective receptors. These, in turn, may be determined genetically. Without effective levels of insulin, cells cannot remove glucose from the bloodstream. As a result, the liver, brain, and other tissues "starve" despite the ready supply. The kidneys work to remove the excess glucose, resulting in the loss of large amounts of water. This produces the symptoms of copious production of sweet urine, thirst, and dehydration.

Hydrocortisone creams are used in the treatment of rashes or excessive itching. These symptoms are overreactions of the immune or nervous systems. However, these medicines should never be applied to wounds, because they inhibit the inflammation response that would otherwise speed healing.

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