AP Ch 21 Mechanisms of Hormonal Regulation PDF

## SUMMARY REVIEW ### Mechanisms of Hormonal Regulation 1. The endocrine system has diverse functions: - reproductive and CNS differentiation - sequential growth and development - coordination of reproductive systems - continuous maintenance of the body's internal environment -...

## SUMMARY REVIEW ### Mechanisms of Hormonal Regulation 1. The endocrine system has diverse functions: - reproductive and CNS differentiation - sequential growth and development - coordination of reproductive systems - continuous maintenance of the body's internal environment - adaptive responses to stress 2. Hormones are chemical messengers synthesized by endocrine glands and released into the circulation. They work with the nervous and immune systems to maintain communication and control. 3. Hormones have specific: - negative-feedback mechanisms - positive-feedback mechanisms Most hormone levels are regulated by negative feedback, in which tropic hormone secretion raises the level of a specific hormone. The elevated level of the specific hormone then causes negative feedback, decreasing secretion of the tropic hormone. Positive feedback systems, in which elevated hormone levels increase a response which then further increases hormone secretion, are most often seen in reproductive hormones. 4. In addition to negative and positive feedback systems, endocrine feedback is described in terms of the levels of feedback (long and short feedback loops). 5. Endocrine communications occur: - within cells (autocrine) - between cells (paracrine) - between remote cells (endocrine) 6. Water-soluble hormones circulate throughout the body in unbound form. Whereas lipid-soluble hormones (i.e., steroid and thyroid hormones) circulate throughout the body bound to carrier proteins. 7. Hormones affect only cells with appropriate receptors (target cells) and then act on those cells to initiate specific cell functions or activities. ### Structure and Function of the Endocrine Glands 1. The hypothalamic-pituitary axis (HPA) forms the structural and functional basis for central integration of the neurologic and endocrine systems. 2. The pituitary gland, consisting of anterior and posterior portions, is connected to the central nervous system through the hypothalamus. 3. The hypothalamus regulates anterior pituitary function by secreting releasing hormones into the portal circulation. 4. Hypothalamic hormones include: - dopamine, which inhibits prolactin secretion - TRH, which affects release of thyroid hormones - CRH, which facilitates release of ACTH and endorphins - substance P, which inhibits ACTH release and stimulates release of a variety of other hormones - ADH and oxytocin are synthesized in the hypothalamus and stored and secreted by the posterior pituitary. 5. The posterior pituitary stores and secretes oxytocin and ADH, also called arginine-vasopressin. 6. ADH controls serum osmolality, increases the permeability of the renal tubules to water, and causes vasoconstriction when administered pharmacologically in high doses. ADH also may regulate some central nervous system functions. 7. Oxytocin causes uterine contraction and lactation in women and may have a role in sperm motility in men. In men and women, oxytocin has an antidiuretic effect similar to that of ADH. 8. The majority of the hormones of the anterior pituitary are regulated by: - secretion of hypothalamic-releasing hormones or factors - negative feedback from hormones secreted by target organs - mediating effects of neurotransmitters. Prolactin is regulated by a positive feedback system. 9. Hormones of the anterior pituitary include: - ACTH - MSH - somatotropic hormones (GH and prolactin) - glycoprotein hormones (FSH, LH, and TSH) 10. Growth hormone stimulates: - bone growth - increased protein metabolism in muscles - lipolysis - Its anabolic effects are mediated in part by IGFs, of which IGF-1 is the most biologically active. 11. Prolactin functions to produce milk during pregnancy and lactation. 12. The pineal gland produces melatonin, which affects: - sleep - circadian rhythms - secretion of GHRH onset of puberty - immune function - aging. 13. The two-lobed thyroid gland contains: - follicles, which secrete the thyroid hormones - parafollicular cells (C cells), which secrete calcitonin and, in smaller quantities, the neuropeptides ghrelin, serotonin, and somatostatin. 14. Regulation of TH levels is complex and involves: - the hypothalamus (TRH) - anterior pituitary (TSH) - thyroid gland - numerous biochemical variables. 15. TH secretion is regulated by TRH through a negative-feedback loop that involves the anterior pituitary and hypothalamus. 16. TSH, which is synthesized and stored in the anterior pituitary, stimulates secretion of TH by activating intracellular processes, including uptake of iodine necessary for the synthesis of TH. 17. Synthesis of TH depends on the glycoprotein thyroglobulin, which contains a precursor of TH, tyrosine. Tyrosine then combines with iodide to form precursor molecules of the thyroid hormones T₁ and T3. 18. When released into the circulation, T3 and T₄ are bound by carrier proteins in the plasma that store these hormones and provide a buffer for rapid changes in hormone levels. 19. Thyroid hormones alter protein synthesis and have a wide range of metabolic effects on proteins, carbohydrates, lipids, and vitamins. TH is responsible for growth, maturation, and function of cells and body systems throughout the body and across the life span. 20. The paired parathyroid glands normally are located behind the upper and lower poles of the thyroid gland. These glands secrete PTH, the single most important regulator of serum calcium and phosphate levels. 21. PTH secretion is regulated by levels of ionized calcium in the plasma and by cAMP within the cell. Some other substances— hormones, neurotransmitters, and ions—affect PTH secretion by inhibiting cAMP or by changing calcium levels. 22. In bone, PTH causes bone breakdown and resorption. In the kidney, PTH increases reabsorption of calcium, decreases reabsorption of phosphorus and bicarbonate, and stimulates synthesis of the active form of vitamin D. Paradoxically, low-dose PTH, administered intermittently, stimulates bone formation. 23. Parathyroid hormone-related peptide (PTHrP) has properties similar to those of PTH and plays a role in placental calcium transport, lactation, and fetal tooth development. 24. The endocrine pancreas contains the islets of Langerhans, which secrete hormones responsible for much of the carbohydrate metabolism in the body. 25. The islets of Langerhans consist of alpha cells, beta cells, delta cells, and F cells. 26. Alpha cells produce glucagon, which is secreted inversely to blood glucose concentrations and stimulates glycogenolysis, gluconeogenesis, and lipolysis. 27. Beta cells synthesize insulin, a hormone that regulates blood glucose concentrations and overall body metabolism of fat, protein, and carbohydrates. Secretion of insulin is regulated by chemical, hormonal, and neural control. Biological responsiveness to insulin is affected by age, weight, abdominal fat, and physical activity. 28. Beta cells also secrete amylin, which promotes glucose-dependent insulin secretion, inhibits glucagon synthesis, and delays gastric emptying, producing an antihyperglycemic effect. 29. Delta cells secrete pancreatic somatostatin, which inhibits secretion of glucagon, insulin, and polypeptide. 30. F cells secrete pancreatic polypeptide, which stimulates Y receptors, promotes gastric secretion, and antagonizes cholecystokinin. 31. Incretin hormones are produced by endocrine cells of the gastrointestinal tract and promote glucose-dependent insulin secretion, inhibit glucagon synthesis, and delay gastric emptying. 32. The paired adrenal glands are situated on the kidneys. Each gland consists of an adrenal medulla, which secretes catecholamines, and an adrenal cortex, which secretes steroid hormones. 33. The steroid hormones secreted by the adrenal cortex are all synthesized from cholesterol. These hormones include glucocorticoids, mineralocorticoids, and adrenal androgens and estrogens. 34. Glucocorticoids directly affect carbohydrate metabolism by increasing blood glucose concentration through gluconeogenesis in the liver and by decreasing use of glucose. Glucocorticoids also inhibit immune and inflammatory responses, inhibit bone formation and ADH secretion, and stimulate gastric secretion. 35. Cortisol secretion is related to secretion of ACTH, which is stimulated by CRH. ACTH binds with receptors of the adrenal cortex, which activates intracellular mechanisms (specifically cAMP) and leads to cortisol release. 36. Mineralocorticoids, especially aldosterone, are steroid hormones that directly affect ion transport by epithelial cells, causing sodium retention and potassium and hydrogen loss. 37. Aldosterone secretion is controlled by the renin-angiotensin-aldosterone system and acts by binding to a site on the cell nucleus and altering protein production within the cell. Its principal site of action is the kidney, where it causes sodium reabsorption and potassium and hydrogen excretion. 38. Androgens and estrogens secreted by the adrenal cortex act in the same way as those secreted by the gonads. 39. The adrenal medulla secretes the catecholamines epinephrine and norepinephrine. Catecholamines are synthesized from the amino acid phenylalanine. Their release is stimulated by sympathetic nervous system stimulation, ACTH, and glucocorticoids. 40. Catecholamines bind with various target cells and are taken up by neurons or excreted in the urine. They cause a range of metabolic effects that generally are characterized as the "fight or flight" response. 41. The endocrine system acts together with the nervous and immune systems to respond to stressors, providing an integrated and protective response. 42. Several assay methods are used to measure levels of hormones in the plasma. RIA compares the proportion of radiolabeled and nonradiolabeled hormone against standard reference curves. 43. ELISA is a method similar to RIA, but uses a radiolabeled enzyme rather than a radiolabeled hormone. 44. Bioassays use graded doses of hormone, a reference preparation, and then compare the results with an unknown sample to determine the hormone level. ### Aging and the Endocrine System 1. Endocrine changes that may be associated with aging include: - altered biologic activity of hormones - altered circulating levels of hormones - altered secretory responses of endocrine glands - altered metabolism of hormones - loss of circadian control of hormone release - changes in secretion of hypothalamic regulatory hormones. 2. Cellular damage associated with aging, genetically programmed cell change, and chronic wear and tear may contribute to endocrine gland dysfunction or alterations in the responsiveness of target organs. 3. Aging apparently causes atrophy of the thyroid gland and is associated with infiltrative glandular changes. Secretion of thyroid hormones may diminish with age. 4. Aging causes pancreatic fat deposition and is associated with a decrease both in insulin secretion and in insulin sensitivity. In addition, there is an age-dependent decline in beta-cell function. 5. Growth hormone levels decrease with aging, leading to decreased bone and muscle mass. 6. Aging is associated with alterations in calcium steady states, which may be related to alterations in PTH secretion from the parathyroid glands. 7. Age-related changes in adrenal function include decreased clearance of glucocorticoids and a decrease in levels of adrenal androgens. The effects of these changes, however, are offset by feedback mechanisms that maintain glucocorticoid levels and by gonadal secretion of androgens. 8. The kidney, choroid plexus, and parathyroid gland secrete the Klotho protein, which has antiaging effects.