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					Chapter 20 Mechanisms of Hormonal Regulation Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. Endocrine System  Functions      Differentiation of the reproductive and central nervous systems in the developing fetus Stimulation of sequential growth and development during childhood and adolescence Coordination of the male and female reproductive systems Maintenance of an optimal internal environment Initiation of corrective and adaptive responses when emergency demands occur Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 2 Hormones  General characteristics  Specific rates and rhythms of secretion • Diurnal, pulsatile and cyclic, and patterns depending on circulating substances    Operate within feedback systems Affect only cells with appropriate receptors The liver inactivates hormones, rendering the hormones more water soluble for renal excretion OR hormones are excreted by kidneys directly Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 The Endocrine System Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Regulation of Hormone Release  Hormones are released:  In response to an alteration in the cellular environment  To maintain a regulated level of certain substances or other hormones    Hormones are regulated by chemical, hormonal, or neural factors Negative feedback Positive feedback Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 5 Feedback Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 Hormone Transport  Hormones are released into the circulatory system by endocrine glands   Water-soluble hormones circulate in free, unbound forms Lipid soluble hormones are primarily circulating bound to a carrier Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Cellular Mechanism of Hormone Action   Target cell Up-regulation   Down-regulation   Low concentrations of hormone increase the number of receptors per cell High concentrations of hormone decrease the number of receptors Hormone effects   Direct effects Permissive effects Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Cellular Mechanism of Hormone Action  Hormone receptors   Water-soluble hormones    Located in or on the plasma membrane or in the intracellular compartment of target cell High molecular weight Cannot diffuse across the plasma membrane Lipid-soluble hormones  Easily diffuse across the plasma membrane and bind to cytosolic or nuclear receptors Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Cellular Mechanism of Hormone Action  Water-soluble hormones    First messenger Signal transduction Second-messenger molecules • Calcium • Cyclic adenosine monophosphate (cAMP) • Cyclic guanosine monophosphate (cGMP) Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Cellular Mechanism of Hormone Action  Lipid-soluble hormones  Steroid hormones • Androgens, estrogens, progestins, glucocorticoids, mineralocorticoids, thyroid   Diffuse across the plasma membrane • Bind to cytoplasmic or nuclear receptors Activate • RNA polymerase • DNA transcription and translation Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 Structure and Function of the Endocrine Glands  Hypothalamic-pituitary axis   Hypothalamus Pituitary gland • Anterior pituitary (adenohypophysis) • Posterior pituitary (neurohypophysis) Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 The Pituitary Gland Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Posterior Pituitary Hormones   Synthesized with binding proteins in supraoptic and paraventricular nuclei of the hypothalamus Secreted by the posterior pituitary  Antidiuretic hormone (ADH, formerly called vasopressin) • Controls plasma osmolality  Oxytocin • Uterine contractions and milk ejection in lactating women • Suggested: reduces the brain’s responsiveness to stressful stimuli, especially in the pregnant and postpartum states  Treatment of anxiety disorders and autism being explored Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Posterior Pituitary Hormones Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Anterior Pituitary Hormones          Adrenocorticotropic hormone Melanocyte-stimulating hormone Growth hormone Prolactin Thyroid-stimulating hormone Luteinizing hormone Follicle-stimulating hormone β-lipotropin β-endorphins Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Anterior Pituitary Hormones Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 17 Thyroid and Parathyroid Glands  Thyroid gland      Two lobes lateral to the trachea Isthmus Follicles (follicle cells surrounding colloid) Parafollicular cells (C cells) • Secrete calcitonin Regulation of thyroid hormone secretion • Thyrotropin-releasing hormone and thyroid-stimulating hormone Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Thyroid and Parathyroid Glands  Thyroid hormones    90% T4 and 10% T3 Bound to thyroxine-binding globulin, thyroxinebinding prealbumin, or albumin Affect growth and maturation of tissues, cell metabolism, heat production, and oxygen consumption Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Thyroid and Parathyroid Glands Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 20 Thyroid and Parathyroid Glands  Parathyroid glands   Small glands located behind the upper and lower poles of the thyroid gland Produce parathyroid hormone • Regulator of serum calcium • Antagonist of calcitonin Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Parathyroid Glands Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Endocrine Pancreas   The pancreas is both an endocrine (producing hormones glucagon, insulin) and an exocrine gland (producing digestive enzymes) Houses the islets of Langerhans  Secretion of glucagon and insulin  Cells • Alpha—glucagon • Beta—insulin • Delta—somatostatin and gastrin • F cells—pancreatic polypeptide Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Endocrine Pancreas Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 24 Endocrine Pancreas Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 25 Endocrine Pancreas  Insulin  Regulated by chemical, hormonal, neural mechanisms  Synthesized from proinsulin  Secretion promoted by increased blood glucose levels  Facilitates rate of glucose uptake into body’s cells • Sensitivity of the insulin receptor is a key component in maintaining normal cellular function (insulin resistance)  Facilitates the intracellular transport of potassium  Anabolic hormone • Synthesis of proteins, lipids, and nucleic acids Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 26 Endocrine Pancreas  Glucagon    Insulin antagonist Secretion promoted by decreased blood glucose levels Stimulates glycogenolysis, gluconeogenesis, and lipolysis Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Endocrine Pancreas  Somatostatin   Produced by delta cells of the pancreas Little is known • In animal studies found to be involved in the regulation of alpha cell and beta cell function • May inhibit glucagon and insulin secretion • May prevent excess secretion of insulin Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 28 Endocrine Pancreas  Gastrin   Likely controls the secretion of glucagon Grehlin    Stimulates GH secretion Controls appetite Regulation of insulin sensitivity Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 29 Endocrine Pancreas  Pancreatic polypeptide      Released by F cells in response to hypoglycemia and protein-rich meals Signals satiety Inhibits gallbladder contraction and exocrine pancreas secretion Increases gastric acid secretion Frequently increased in pancreatic tumors and in diabetes Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 30 Endocrine Pancreas Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 31 Adrenal Glands  Adrenal cortex      80% of an adrenal gland’s total weight Zona glomerulosa Zona fasciculata Zona reticularis Adrenal medulla  Innervated by the sympathetic and parasympathetic nervous systems Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 32 Adrenal Glands  Adrenal cortex   Stimulated by adrenocorticotropic hormone (ACTH) Glucocorticoid hormones • Direct effects on carbohydrate metabolism • Anti-inflammatory, growth-suppressing effects • Influence awareness and sleep habits • Most potent naturally occurring glucocorticoid is cortisol Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 33 Adrenal Glands  Adrenal cortex  Mineralocorticoid hormones • Affect ion transport by epithelial cells   Increase the activity of the sodium pump of the epithelial cells Cause sodium retention and potassium and hydrogen loss • Most potent naturally occurring mineralocorticoid is aldosterone  Regulated by the renin-angiotensin-aldosterone system Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 34 Aldosterone Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 35 Adrenal Glands  Adrenal cortex  Adrenal estrogens and androgens • Estrogen secretion by the adrenal cortex is minimal • The adrenal cortex secretes weak androgens  Androgens converted by peripheral tissues to stronger androgens such as testosterone Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 36 Adrenal Glands  Adrenal medulla  Chromaffin cells (pheochromocytes) • Chromaffin cells secrete the catecholamines epinephrine (majority) and norepinephrine   Release of catecholamines has been characterized as a “fight or flight” response Catecholamines promote hyperglycemia Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 37 Catecholamines Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 38 Neuroendocrine Response to Stress    The endocrine system reacts with the nervous system to respond to stressors The stress response also involves the immune system Influenced by corticotropin-releasing hormone from the hypothalamus Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 39 Tests of Endocrine Function    Radioimmunoassay Enzyme-linked immunosorbent assay (ELISA) Bioassay Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 40 Aging and the Endocrine System   Endocrine changes: consequence or cause? Thyroid gland   Parathyroid glands   Glandular atrophy, fibrosis, nodularity, and increased inflammatory infiltrates Related to alterations in calcium balance • Inadequate intake, malabsorption, or renal changes Adrenal glands  Decreased clearance of cortisol Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 41
 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                            