Endocrine Control of Growth
and Metabolism

LECTURE OUTLINE (CHAPTERS 22 and 23)

LECTURE OBJECTIVES

1. Describe the structure and function of the "classical" endocrine glands.
2 . Explain the regulation and actions of Insulin and Glucagon on glucose.
3 . Discuss fuel metabolism in general and establish that its regulation results from an interplay of multiple hormonal systems.
4 . Describe how hormones regulate fuel metabolism during (=absorptive) and between (=postabsorptive) meals.
5. Explain the regulation and actions of hormones from the adrenal cortex and adrenal medulla.
6 . Describe how the adrenal gland is involved in acute and chronic stress.
7. Explain the unique way that Thyroid Hormones are synthesized and secreted, what regulates their levels in the blood, and how they act.
8 . Review bone structure and its deposition/resorption.
9. Explain the regulation and actions of Growth Hormone, the role of Insulin-like Growth Factors in growth, and the disorders that result from too little or too much Growth Hormone.
10. Explain the regulation and actions of Parathyroid Hormone and Calcitonin on Ca++ metabolism and describe how Calcitriol is involved in this process.
11. Discuss how hyperfunction and hypofunction of an endocrine gland leads to disease and provide examples.

LECTURE OUTLINE

I. INTRODUCTION

   A. Important peripheral endocrine glands (pancreas, adrenal, thyroid, 
       and parathyroid)

II. PANCREAS

  A. Structure
       1. Islet of Langerhans
           a. Beta cells secrete insulin
           b. Alpha cells secrete glucagon 
  B. Insulin Function
      1. Insulin lowers blood glucose and promotes nutrient storage following a meal
      2. Direct regulation through plasma glucose
          a. Insulin acts through glucose transporters (e.g., GLUT 4)
      3. Hypofunction:  Diabetes mellitus
          a. Distinctions between Type I and Type II diabetes
          b. Body Mass Index (BMI) and health risk
             a. Calculate your BMI
  C. Glucagon Function  
      1. Role of glucagon between meals and during fasting
      2. Glucagon promotes catabolism of fuel stores
         	a. Catabolism of fats, protein, and glycogen in liver cells
      3. Glucagon causes hyperglycemia in diabetics.  

III. ADRENAL GLAND

   A. Structure
        1. Adrenal cortex and medulla
   B. Function of Cortex
        1. Aldosterone regulates Na+ retention
        2. Cortisol effects on cellular metabolism
            a. Enhances gluconeogenesis
            b. Anti-inflammatory action; suppresses immune response
   C. Regulation of Adrenal Cortex
   D. Hypofunction and Hyperfunction 
        1. Cushing's Disease
            a. Symptoms and treatment
        2. Addison's Disease
            a. Symptoms and treatment  
   E. Functions of adrenal medulla--Role in acute stress
        1. Relationship to Sympathetic Nervous System
            a. Epinephrine has multiple effects 
        2. "Fight or flight" response of W.B. Cannon
   F. General Adaptation Syndrome of H Seyle-- Response to chronic stress
       1. Non-specific stressors elicit this syndrome
       2. Roles for Epinephrine, Cortisol, and ACTH

IV. THYROID GLAND

   A. Structure of the Thyroid
        1. Follicles enclose colloid
   B. Synthesis, Storage, Release, and Transport of Thyroid Hormone
        1. Synthesis in colloid on thyroglobulin        
            a. Roles of iodine and tyrosine in T3/T4 synthesis
        2. Storage and Secretion of thyroid hormone
        4. Transport in blood
   C. Physiological Effects
        1. Increases BMR 
        2. Accelerates protein synthesis in children
        3. Enhances sympathetic tone (sympathomimetic effect on heart, brown fat)
   D. Regulation of thyroid hormone
        1. Roles of TRH, TSH, stress, and cold in regulation  
   E. Hypofunction and Hyperfunction (if time permits)
        1. Myxedema and Cretinism (in children)
        2. Grave's disease 
        3. Goiter

V. THE ENDOCRINOLOGY OF GROWTH

  A. Growth Hormone (GH) and other factors affect growth
  B. Peripheral Effects of GH
     1. GH stimulates Insulin-like Growth Factors from the liver
  C. Regulation of Growth Hormone
     1. GH inhibitory hormone (=Somatostatin) and GH releasing hormone
  D. Abnormalities in GH Secretion (if time permits)
     1.  Hyposecretion:  Dwarfism
     2.  Hypersecretion:  Gigantism and acromegaly 

VI. PARATHYROID GLAND REGULATES CALCIUM

  A. Structure
       1. Found embedded in thyroid
  B. Function
      1. PTH is the principal regulator of plasma Ca++
          a. Why regulate plasma Ca++?
          b. PTH regulates Ca++ via kidney reabsorption, instestinal 
              absorption, and active transport from the "bone pool" 
  C. Regulation
      1. Direct regulation of PTH via plasma Ca++
  D. Other hormones involved in Ca++ balance  
      1. Calcitonin from thyroid acts in opposition to PTH
      2. Calcitriol is derived from Vitamin D and raises plasma Ca++
          a. It enhances Ca++ absorption from intestine
          b. PTH acts synergistically with Calcitriol
  E. Hyperfunction and Hypofunction.
      1. Hyperparathyroidism
      2. Hypofunction: Vitamin D deficiency  
          a. Rickets in children
  F. Osteoporosis (if time permits)
  G. Summary of Ca++ Balance

Reading Assignment. Please read Chapter 26 for the next lecture.


STUDY QUESTIONS ON ENDOCRINE CONTROL OF GROWTH/METABOLISM
(CHAPTERS 22 and 23)

    BASIC FACTS AND TERMS

  1. Important Study Question. For each of the following hormones: 1) List the endocrine gland that secretes the hormone; 2) Identify the hormone as a steroid, amine, or peptide; 3) List its actions; and 4) Describe the mechanism(s) that regulates the hormone (if appropriate).
    Growth hormone (GH) Calcitonin
    Parathyroid Hormone (PTH) Cortisol (F)
    Aldosterone Epinephrine (E)
    Secretin Cholecystokinin (CCK)
    Somatostatin (SS) Insulin
    Glucagon Gastrin
    Thyroid hormone (T3 and T4) Renin
    Ghrelin Glucose-dependent insulinotrophic peptide (GIP)
    Calcitriol  

  2. Compare the adrenal cortex and adrenal medulla with regard to location and histology.

  3. Identify the endocrine gland at the tip of the arrows.





  4. Where are the parathyroids located? What is their histology? What are the functions of parathyroid hormone (PTH) at the bone and kidney?

  5. Describe the General Adaptation Syndrome (GAS) in response to a stressor. What are the phases of the GAS? How does the hypothalamus coordinate this syndrome? What hormones are involved and what does each do?

  6. Define and give the physiological significance (how or why it is important) for the following terms:

    • Glucocorticoid
    • Mineralocorticoid
    • Islet of Langerhans (alpha and beta cells)
    • Thyroxine-binding globulin
    • Thyroglobulin
    • Thyroid-stimulating immunoglobulin (TSI)
    • Insulin shock
    • Colloid (in thyroid gland)
    • Gluconeogenesis
    • Glycogenesis
    • Glycogenolysis
    • Lipolysis
    • Lipogenesis
    • Insulin-like growth factors (IGF)

  7. Distinguish between Type I and Type II diabetes mellitus with respect to: 1) age of onset, nature of the hormone defect, 2) level of insulin secretion, 3) extent of ketosis, 4) metabolism of various nutrients, and 5) treatment. What factors contribute to Type II diabetes? What is insulin resistance?

  8. In the center box write the hormone or hormones that directly regulate the following physiological conversions.Your answer to #1 should help here.

    glucose to                                 glycogen
    amino acids to   glucose
    protein to   amino acids
    glucose to   fats (triglycerides)
    glycogen to   glucose
    low blood glucose to   high blood glucose
    high blood glucose to   low blood glucose
    fats (triglycerides) to   fatty acids
    fatty acids   fats (triglycerides)

  9. What are the causes, symptoms, and treatment for the following endocrine disorders?
    Cushing's disease (=syndome) Myxedema
    Exopthalmia Addison's disease
    Hyperparathyroidism Diabetes mellitus
    Rickets Cretinism
    Grave's disease Goiter

  10. Hormones are found in many different organs, not just the traditional endocrine glands. Complete the following exercise to test how well you know these organs and the hormones they secrete: click here


    CONCEPTS

  11. Describe the location and histology of the thyroid gland. How are thyroid hormones synthesized, stored, and secreted in the gland and transported in the blood? Which of these thyroid hormones is the more potent?

  12. "Three meals a day" is our routine, but how is periodic eating handling internally? Specifically, how does the endocrine system maintain internal homeostatic processes, such as blood glucose, in the face of our "feast or famine" pattern of eating? Explain.

  13. What are glucose transporters (GLUT), how are they important, and where are they found? How does insulin act on these transporters to increase glucose uptake by insulin-sensitive cells? (See pages 732-733). Are all cells insulin-sensitive? Defend your answer.

  14. What is goiter? What underlying factors cause it? How can hypofunction and hyperfunction nof the regulatory system both result in goiter? Explain.

  15. What is the relationship between the adrenal medulla and the sympathetic nervous system? How are the actions of epinephrine similar to the sympathetic nervous system? Different?

  16. What is the "fight or flight" response (=acute stress)? Make a list of how epinephrine (an a little norepinephrine) mobilizes the body for a "fight or flight" response? How does epinephrine work at its target site and what is its half life in circulation? (See Table 22-4)

  17. Read about bone growth in the text (pages 764--766). Also read about osteoporosis. What is the hormonal basis for greater occurrence of osteoporosis in menopausal women? What remedies exist to prevent osteoporosis? See page 771 in the text.

  18. Hyperfunction of an endocrine gland can result from a number of conditions. List some of the possibilities. List possibilities for hypofunction of an endocrine gland. What general treatments are used to counter hypersecretion of a hormone? Treatments for hyposecretion of a hormone?

  19. How does Growth Hormone (GH) regulate growth? What other hormones and non-endocrine influences also influence growth processes? Explain the control of GH secretion. Outline the control mechanisms.

  20. How does interaction of multiple hormones influence the growth spurt of boys and girls at puberty? What sex differences exist in growth? What is the hormonal basis for these differences?

  21. Why must plasma Ca++ be closely regulated? How is Parathyroid Hormone (PTH) involved in Ca++ regulation? What are our major Ca++ sources? What is Calcitonin and what is its role in Ca++ regulation? What is Calcitriol's role? See Figures 23-20 and 23-23.

  22. How are Ca++ and PO4--- ions regulated in the plasma? What is the relationship between these two ions? See page 770.

  23. What are the sources of Vitamin D? What is the role of Vitamin D in Ca++ regulation? How does Vitamin D deficiency lead to bone thinning? Explain.


    REASONING AND PROBLEM SOLVING

  24. Why is it recommended that individuals who are allergic to bee stings and thus are at risk for anaphylactic shock carry a vial of injectable epinephrine in case of bee sting?

  25. African pigmies lack the normal bone growth present in most people, and this lack results from a genetic mutation. Growth Hormone (GH) titer in the blood is normal so that hormone is probably not responsible. Given your understanding of the processes controlling growth, provide a short physiological explanation as to what might be absent in pigmies that results in their short stature? There are a couple of possibilities. What are they? Explain your answers.

  26. Grandma Moses is receiving very large doses of cortisol-like drug to treat her arthritis. As a result of this drug treatment, what would most likely happen to her adrenal gland function? Explain.

  27. Propylthiouracil is a drug which blocks the synthesis of both T3 and T4 in the thyroid gland. With chronic propylthiouracil treatment, what physiological changes would you expect across time in circulating Thyroid hormone, Thyroid Stimulating Hormone, and in the anatomy of the thyroid gland itself? Briefly defend your answers..

  28. Tim suffers from diabetes mellitus, but he has normal levels of circulating insulin. How would you explain that apparent inconsistency?

  29. People who exhibit hyperthyroidism (high plasma titers of T3 and T4) usually have low fat stores. Given your understanding of thyroid hormone function, what is a probable cause for low fat stores? Explain.

  30. (Ignore. Subject not presented in 2008) The bearded lady in the circus side show probably suffered from what endocrine disorder? Explain.

  31. A patient with symptoms of hyperthyroidism is found to have circulating antibodies against the receptors for both thyroid hormones, T3 and T4. Given your understanding of the immune system, can you deduce the cause of hyperthyroidism in this case?

  32. Goiter, the enlargment of the thyroid gland, can result from either hyperthyroidism or hypothyroidism. Explain how this same physical manifestation in the thyroid gland can occur in these two opposite conditions. What criterion might you use to distinguish between the effect of hyperthroidism and hypothyroidism?

  33. In some diabetic individuals with hyperglycemia, Glucagon is actively secreted which elevates blood glucose even more. Given your knowledge how Glucagon is regulated in the pancreas, propose a mechanism that would result in Glucagon secretion even though blood sugar is high.


Last revised: April 17, 2008