Mechanisms of Hormonal Regulation

1. Mechanisms of Hormonal Regulation Chapter 17

2. The Endocrine System • Functions • Differentiation of reproductive and CNS in fetus • Stimulation of growth and development • Coordination of the male and female reproductive system • Maintenance of internal environment • Adaptation to emergency demands of the body

4. Hormones • General characteristics • Specific rates and rhythms of secretion • Diurnal, pulsatile and cyclic and patterns depend upon circulating substances • Operate within feedback systems (+/-) • Affect only target cells with appropriate receptors • The liver inactivates hormones, rendering the hormones more water soluble for renal excretion

5. 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 • Mechanism – release • Chemical factors (blood sugar , Ca++ levels) • Endocrine factors (FSH → ovary → E) • Neural control (CRF → pituitary → ACTH) Feedback

7. Hormone Transport (Table 17-1) • Hormones are released into the circulatory system by endocrine glands • Water-soluble hormones circulate in free unboundforms • Short-acting responses • Bind to surface receptors • Lipid-soluble hormones are primarily circulating bound to a carrier (Table 17-2) • Rapid and long-lasting response • Bind to cytoplasm or nucleoplasm receptor

8. Cellular Mechanisms of Hormone Action • Target cell – recognize, bind and initiate • Up – regulation • Down – regulation • Hormone effects • Direct – stimulation • Permissive– facilitates maximum response/function

10. Cellular Mechanisms of Hormone Action • Hormone receptors • Located in the plasma membrane or in the intracellular compartment of the target cell • Water-soluble hormones (peptides) • High molecular weight • Cannot diffuse across the plasma membrane

11. Cellular Mechanisms of Hormone Action • Lipid-soluble hormones • Easily diffuse across the plasma membrane and bind to cytoplasm or nuclear receptors

13. Cellular Mechanisms of Hormone Action • Water-soluble hormones • First messenger • Signal transduction • Second messenger molecule (Table 17-3) • Calcium • Cyclic adenosine monophosphate (cAMP) • Cyclic guanosinemonophosphate (cGMP) • Tyrosine kinase system

15. Cellular Mechanisms of Hormone Action • Lipid-soluble hormones • Steroid hormones • Androgens, estrogens, progestins, glucocorticoids, mineralocorticoids, thyroid hormones, vitamin D, retinoid • Diffuse across the plasma membrane • Bind to cytoplasmic or nuclear receptors • Activate DNA transcriptn and translation

16. Steroid Hormone Mechanism

17. Structure and Function of the Endocrine Glands • Hypothalamus • Pituitary gland • Anterior pituitary (adenohypophysis) A) Chromophobes – non-secretory cells B) Chromophils - secretory cells 7 cell types → specific hormones

21. Structure and Function of the Endocrine Glands • Pituitary gland • Posterior pituitary(neurohypophysis) • Synthesized with binding proteins in the neurons of the supraoptic and paraventricular nuclei of the hypothalamus → stored • Anti-diuretic hormone (ADH) • Oxytocin

23. Nerve Tracts: Hypothalamus to Posterior Pituitary

24. Control of Posterior Pituitary Hormones • Release (both) • Stimulation of cholinergic receptors by Ach, angiotensin II, and B-endorphins • Inhibition • B-adrenergic receptors

25. Posterior Pituitary • Anti-diuretic hormone • Controls plasma osmolality • ↑ permeability of distal renal tubules and collecting ducts • Pharmacological levels ADH (vasopressin) → vasoconstriction and ↑ BP • Regulation • Osmoreceptorsof the hypothalamus • Baroreceptors: L atrium, carotid and aortic arches (intravascular volume) also: stress, trauma, pain, exercise, nausea, nicotine, heat, morphine → ↑ secretion, ↓ HTN, alcohol and ↑ plasma volume

26. Oxytocin • Uterine contractions and milk ejection with lactation • Role in sperm motility in men • ADH effect-weak

27. Thyroid Gland “controls the rate of metabolic processes” • Bilobed either side of trachea – joined by isthmus • Follicles – follicle cells surrounding colloid • Parafollicular cells (C cells) • Secretecalcitonin (↓ serum Ca++ by # bone – resorption) • Regulation • Thyrotropin – releasing hormone and thyroid stimulating hormone

28. Thyroid Gland • Thyroid hormones • Iodine – required for synthesis • 90% T4 and 10% T3 • Bound to thyroxine - binding globulin - mostly • Regulation - negative feedback • TRH - ↑ cold exposure, stress and ↓ T4 • Effects • ↑ metabolism of protein, fat and glucose → rapid ↑ heat production and body temperature • Normal linear growth requires TH • CNS and ANS require TH

29. Thyroid Follicle Cells

30. Thyroid and Parathyroid Glands

31. Parathyroid Glands • Parathyroid hormone • ↑ Ca++ and↓ PO4= - bone, kidneys • Antagonist of calcitonin

32. Thyroid and Parathyroid Glands

33. Endocrine Pancreas • The pancreas is both an endocrine and an exocrine gland • Islets of Langerhans • Secretion of glucagon and insulin • Cells • Alpha – glucagon • Beta – insulin • Delta – somatostatin and gastrin • F cells – pancreatic polypeptide

34. Endocrine Pancreas

35. Endocrine Pancreas • Insulin • Synthesized from proinsulin • Secretion is promoted by ↑ blood glucose • Facilitates the rate of glucose uptake into the cells • Anabolic hormone • Synthesis of proteins, lipids and nucleic acids

36. Endocrine Pancreas • Glucagon • Secretion is promoted by decreased blood glucose levels • Stimulates glycogenolysis, gluconeogenesis and lipolysis • Somatostatin(delta cells) • Regulation alpha and beta cell secretions

37. Endocrine Pancreas

38. Adrenal Glands • Adrenal cortex • 80% of an adrenal gland’s total weight • Zona glomerulosa – aldosterone 15% • Zona fasciculata – glucocorticoids 78% • Zona reticularis – androgens and estrogens (others) • 7% • Adrenal medulla • Innervation by SNS

39. Adrenal Gland & Structural Layers

40. Adrenal Cortex “all hormones derived from cholesterol” • Stimulated by adrenocorticotropic hormone (ACTH) • Glucocorticoid hormones • Direct effect on carbohydrate metabolism • Anti-inflammatory and growth suppression effects • Influences awareness and sleep habits • Inhibits bone matrix-protein matrix • Cortisol– most potent naturally occurring

41. (+) Diurnal rhythms ( - ) Hypothalamus Corticotropin-releasing factor (CRF) Stress (+) ( - ) Somatostatin Hypothalamic lesions (+) Anterior pituitary Hypoxia Hypoglycemia Hyperthermia Exercise Cortisol insufficiency Adrenocorticotropic hormone (ACTH) Adrenal cortex Glucocorticoids (especially cortisol)

42. Adrenal Cortex • Mineralocorticoid hormones – Aldosterone • ↑ Na+ uptake in epithelial cells – distal nephrons • ↑ Na retention with loss of K+ and H+ • Regulation by the renin-angiotensin system • Na+ and H2O depletion • ↑ K+ excreteion • ↓ blood volume

43. Nephron

44. Aldosterone

46. Adrenal Cortex • Adrenal estrogens and androgens • Estrogen secretion is minimal (vs. ovary) • Androgens – weak • Converted by peripheral tissues to stronger androgens such as testosterone

47. Adrenal Medulla • Chromaffin cells (pheochromocytes) • Secrete catecholamines – epinephrine andnorepinephrine • “Fight or Flight Response” • SNS, hypoglycemia, hypoxia, hypercapnia, acidosis, hemorrhage, glucagon, nicotine, pilocarpine, histamine and angiotensin II • Epinephrine is 10x more potent than NE • Promote hyperglycemia

48. Catecholamines