Costanzo | Physiology | Chapter 9 | Endocrine Physiology | Study Guide

Chapter 9: Endocrine Physiology Notes

I. Hormone Synthesis and Regulation

• Synthesis Mechanisms:

  • Peptide/Protein Hormones: Synthesized on ribosomes, processed in the rough ER (preprohormone to prohormone), and packaged in the Golgi apparatus into secretory vesicles [885t, 913, 951].

  • Steroid Hormones: Derived from cholesterol; includes cortisol, aldosterone, androgens, estrogen, and progesterone [885t, 887, 928].

  • Amine Hormones: Derivatives of the amino acid tyrosine; includes catecholamines (epinephrine, norepinephrine, dopamine) and thyroid hormones [885t, 887].

• Secretion Regulation:

  • Negative Feedback: The most common mechanism. Some feature of hormone action directly or indirectly inhibits further secretion (e.g., insulin secretion decreasing as blood glucose falls) [886, 888f, 889].

  • Positive Feedback: Uncommon and leads to explosive events (e.g., the estrogen-induced LH surge before ovulation or oxytocin in labor).

• Receptor Regulation: Down-regulation reduces the number/affinity of receptors to decrease sensitivity (e.g., in obesity for insulin receptors); up-regulation increases them to increase sensitivity.

II. Mechanisms of Hormone Action

• Adenylyl Cyclase (cAMP): Uses Gs​ or Gi​ proteins to alter cAMP levels; used by ACTH, LH, FSH, TSH, ADH (V2​ receptors), PTH, and Glucagon [894, 897t, 900f].

• Phospholipase C (IP3​/Ca2+): Hormone binds to Gq​, activating phospholipase C to produce IP3​ and diacylglycerol, which release Ca2+; used by GnRH, TRH, GHRH, Angiotensin II, and ADH (V1​ receptors) [897t, 898, 903f].

• Steroid and Thyroid Hormones: Diffuse into cells to bind cytosolic or nuclear receptors, acting as transcription factors to synthesize new proteins [897t, 908, 910f, 925, 926f].

• Tyrosine Kinase: Involves intrinsic (Insulin, IGF-1) or associated (Growth Hormone, Prolactin) kinase activity [897t, 903, 907f].

III. The Hypothalamic-Pituitary Axis

• Anterior Pituitary (Adenohypophysis): Connected to the hypothalamus via hypothalamic-hypophysial portal vessels. Hormones include TSH, ACTH, FSH, LH, Growth Hormone (GH), and Prolactin [884t, 910].

• Posterior Pituitary (Neurohypophysis): A neural extension of the hypothalamus. Secretes ADH (water reabsorption) and Oxytocin (milk ejection and uterine contraction).

• Growth Hormone: Stimulated by GHRH and inhibited by Somatostatin. Its growth-promoting effects are largely mediated by somatomedins (IGF-1) produced in the liver [916, 917f].

IV. Thyroid, Adrenal, and Pancreatic Hormones

• Thyroid Hormones (T3​,T4​): Synthesized via organification of iodine and coupling of tyrosine residues on thyroglobulin [924t]. T3​ is the more active form, increasing BMR, heat production, and O2​ consumption [925, 926f].

• Adrenal Cortex:

  • Zona Glomerulosa: Produces Aldosterone (mineralocorticoid).

  • Zona Fasciculata/Reticularis: Produces Cortisol (glucocorticoid) and androgens.

• Endocrine Pancreas: Insulin (β cells) promotes nutrient storage (decreases blood glucose); Glucagon (α cells) promotes nutrient mobilization (increases blood glucose) [885t, 940, 942, 946f].

V. Calcium and Phosphate Metabolism

• Parathyroid Hormone (PTH): Secreted when plasma [Ca2+] is low. It increases plasma Ca2+ by stimulating bone resorption, renal Ca2+ reabsorption, and renal Vitamin D activation. It also causes phosphaturia (decreased phosphate reabsorption).

• Vitamin D (1,25-dihydroxycholecalciferol): Activated in the kidney by 1α-hydroxylase (stimulated by PTH). Its primary role is to increase Ca2+ and phosphate absorption in the intestine [954, 961, 962f].

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Chapter 9 Study Guide

I. Glossary of Key Terms

• Acromegaly: Condition caused by excess growth hormone secretion after puberty.

• BMR (Basal Metabolic Rate): The rate of energy expenditure at rest; significantly increased by thyroid hormones.

• Conn Syndrome: Primary hyperaldosteronism caused by an aldosterone-secreting tumor.

• Cushing Disease: Excess cortisol caused by an ACTH-secreting pituitary tumor.

• Gluconeogenesis: The synthesis of glucose from non-carbohydrate sources, stimulated by cortisol and glucagon [926f, 940, 946f].

• Incretin: A gastrointestinal hormone, such as GIP, that stimulates insulin secretion.

• Somatomedins: Insulin-like growth factors (e.g., IGF-1) that mediate the growth-promoting effects of GH.

• Steatorrhea: Excess fat in the stool, often caused by high gastrin levels in Zollinger-Ellison syndrome inactivating lipase.

• Trophic Effect: The growth-promoting effect of a hormone on its target gland (e.g., ACTH on the adrenal cortex).

• Up-Regulation: An increase in the number or affinity of receptors in a target tissue.

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II. 50 Question-and-Answer Quiz

Questions

1. What are the three classes of hormones based on chemical structure?

2. Which precursor is used for all steroid hormones?

3. What amino acid is the precursor for thyroid hormones?

4. Where are peptide hormones primarily synthesized?

5. What is the most common mechanism for regulating hormone secretion?

6. Give an example of hormonal positive feedback.

7. What is the effect of "down-regulation" on a target tissue?

8. Which G protein is associated with the adenylyl cyclase mechanism?

9. Which second messenger is generated by phospholipase C?

10. Which hormones utilize the tyrosine kinase mechanism?

11. How are thyroid hormones transported in the blood?

12. Where are the receptors for steroid hormones located?

13. What is the primary function of the hypothalamic-hypophysial portal system?

14. Which hormones are secreted by the posterior pituitary?

15. Where are ADH and oxytocin synthesized?

16. What is the major stimulus for ADH secretion?

17. Which receptor mediates the water-reabsorptive effect of ADH?

18. What is the effect of ADH on vascular smooth muscle via V1​ receptors?

19. Which hypothalamic hormone inhibits growth hormone secretion?

20. What are the liver-derived mediators of GH's growth effects?

21. What is the metabolic effect of GH on blood glucose?

22. Which condition results from GH excess before puberty?

23. What does Prolactin inhibit in the hypothalamus?

24. Which enzyme catalyzes the organification of iodine in the thyroid?

25. Which is more biologically active: T3​ or T4​?

26. What is the effect of thyroid hormone on the heart?

27. Which thyroid disorder is caused by thyroid-stimulating immunoglobulins?

28. Name the three layers of the adrenal cortex.

29. Which adrenal layer produces aldosterone?

30. What is the primary regulator of aldosterone secretion?

31. What are the major actions of cortisol?

32. Which enzyme deficiency causes virilization and decreased cortisol?

33. What characterizes Addison disease?

34. What are the primary symptoms of Conn syndrome?

35. Which cells in the pancreas secrete insulin?

36. Which cells in the pancreas secrete glucagon?

37. What is the primary stimulus for insulin secretion?

38. How does insulin affect blood potassium levels?

39. What is the major action of glucagon?

40. Which pancreatic hormone inhibits both insulin and glucagon?

41. What percentage of total plasma calcium is ionized (biologically active)?

42. What is the primary regulator of PTH secretion?

43. What is the effect of PTH on bone?

44. Which part of the nephron is the site for PTH-induced phosphate inhibition?

45. What is the effect of PTH on renal calcium handling?

46. Where is Vitamin D converted to its active form?

47. What is the primary action of 1,25-dihydroxycholecalciferol?

48. What causes hypercalciuria in primary hyperparathyroidism?

49. What is the effect of chronic renal failure on Vitamin D levels?

50. Which hormone is secreted by "oat cell" carcinomas of the lung?

Answer Key

1. Peptides/proteins, steroids, and amines. 2. Cholesterol. 3. Tyrosine. 4. Ribosomes. 5. Negative feedback. 6. LH surge or oxytocin in labor. 7. Decreased sensitivity. 8. Gs​ (or Gi​ for inhibition) [894, 897t]. 9. IP3​ and Ca2+. 10. Insulin, IGF-1, GH, and Prolactin [897t]. 11. Bound to plasma proteins (e.g., TBG). 12. Cytosol or nucleus. 13. Deliver hypothalamic hormones to the anterior pituitary. 14. ADH and Oxytocin. 15. Hypothalamic nuclei (supraoptic and paraventricular). 16. Increased serum osmolarity. 17. V2​ receptor. 18. Vasoconstriction. 19. Somatostatin. 20. Somatomedins (IGF-1). 21. Diabetogenic (increased glucose). 22. Gigantism. 23. GnRH. 24. Thyroid peroxidase [924t]. 25. T3​. 26. Increased cardiac output, heart rate, and contractility. 27. Graves disease. 28. Zona glomerulosa, fasciculata, and reticularis. 29. Zona glomerulosa. 30. Angiotensin II and serum [K+]. 31. Gluconeogenesis, anti-inflammatory, and vascular responsiveness [926f, 930]. 32. 21β-hydroxylase. 33. Low cortisol, high ACTH, and skin hyperpigmentation. 34. Hypertension, hypokalemia, and metabolic alkalosis. 35. β cells [885t, 937]. 36. α cells [885t, 942]. 37. Increased blood glucose. 38. Promotes K+ uptake into cells. 39. Mobilize glucose (glycogenolysis, gluconeogenesis) [946f]. 40. Somatostatin. 41. 50%. 42. Decreased plasma [Ca2+]. 43. Stimulates bone resorption. 44. Proximal tubule. 45. Increases Ca2+ reabsorption in the distal tubule. 46. Kidneys. 47. Increase intestinal Ca2+ and phosphate absorption. 48. High filtered load overwhelms reabsorption. 49. Decreased (due to 1α-hydroxylase loss) [955t]. 50. ADH (causing SIADH).

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III. Short Answer Questions

1. Explain the cellular mechanism of insulin secretion from the β cell.

   • Answer: Glucose enters via GLUT2, is metabolized to ATP, which closes K+-ATP channels. This depolarizes the cell, opening voltage-gated Ca2+ channels. Ca2+ influx then triggers the exocytosis of insulin.

2. Contrast "short-loop" and "long-loop" negative feedback.

   • Answer: Long-loop feedback is when a peripheral gland hormone (e.g., cortisol) inhibits the hypothalamus or anterior pituitary. Short-loop feedback is when an anterior pituitary hormone (e.g., TSH) inhibits the hypothalamus [887, 888f, 889].

3. Why does an oral glucose load produce a larger insulin response than an IV one?

   • Answer: Oral glucose stimulates the release of GIP (an incretin) from the intestine, which provides an additional stimulus for insulin secretion beyond the direct effect of glucose.

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IV. Essay Questions

1. Describe the sequence of events in thyroid hormone synthesis, from iodine uptake to hormone release.

   • Focus: Discuss the I− trap (Na+−I− cotransport), synthesis of thyroglobulin, oxidation of I− to I2​ by peroxidase, organification to form MIT/DIT, the coupling reaction to form T3​/T4​, endocytosis of thyroglobulin, and lysosomal hydrolysis for release [924t].

2. Compare and contrast the pathophysiology of Cushing disease and Addison disease.

   • Focus: Cushing involves excess cortisol (usually ACTH tumor), leading to hyperglycemia and muscle wasting. Addison involves adrenal destruction, leading to cortisol and aldosterone deficiency, hypotension, hyperkalemia, and hyperpigmentation.

3. Explain the coordinated role of PTH and Vitamin D in maintaining calcium homeostasis.

   • Focus: Describe how low serum [Ca2+] triggers PTH release. Explain PTH's effects on bone (resorption), kidney (Ca2+ reabsorption and 1α-hydroxylase stimulation), and how active Vitamin D then increases intestinal absorption to restore [Ca2+].