1. Endocrine Physiology Bob Bing-You, MD, MEd, MBA Medical Director Maine Center for Endocrinology

2. What is physiology? A. Study of function in living matter B. Specific characteristics and mechanisms of the human body that make it a living being C. “The human being is actually an automaton.” D. All of the above.

3. Learning Objectives Explain normal feedback mechanisms for normal endocrine function Describe abnormal pathophysiologic states Define treatment approaches for such states

4. Ground Rules Case-based, common examples Feel to ask questions anytime Take a few breaks for Q and A Call or e-mail [bingyb@mmc.org] with confused thoughts, concepts, etc.

5. Major Areas Thyroid gland Adrenal gland function, steroid Rx Diabetes: glucose monitoring, insulin Rx Calcium homeostasis, vitamin D Pheochromocytoma Diabetes insipidus

6. Design Exercise New heat source for your house in the basement Need monitor system 3 floors above Thermostats not invented yet! Task= design system to regulate temperature in your house

7. Purpose of Endocrine System Principally concerned with control of different metabolic functions of the body [e.g., transport of substances through cell membranes] Hormonal effects can occur in seconds while others require days or weeks

8. What is a hormone? A chemical substance secreted into body fluids by one cell or group of cells Exerts a physiological control effect on other cells in the body General vs. local hormones General hormones may effect all cells [e.g. GH] or some effect specific tissues

11. Major Hormones Anterior pituitary –Growth hormone –Adrenocorticotropin [ACTH] –Thyroid-stimulating hormone [TSH] –Follicle-stimulating hormone [FSH] –Luteinizing hormone [LH] –Prolactin [PRL]

13. More Hormones Posterior pituitary: antidiuretic hormone [ADH] Adrenal –Aldosterone –Glucocorticoids [cortisol] –Testosterone, estrogen –catecholamines

14. Even More Hormones! Thyroid hormones: thyroxine [T4], triiodothyronine [T3] Pancreatic: insulin, glucagon Parathyroid: parathyroid hormone [PTH]

15. Chemistry of Hormones Two types –Proteins or derivatives of proteins or amino acids [e.g., anterior pituitary, thyroid] –Steroid hormones [e.g., adrenal cortex, gonads] Circulate in minute quantities [e.g., one- millionth of a milligram] Bioassay vs. radioimmunoassay

16. What describes hormones effecting other local cells? A. Paracrine B. Endocrine C. Autocrine D. None of the above.

17. Bioassay Animal cell tissue system Plasma or some extract added to see effect E.g., testosterone

18. Immunoassay Sandwich-type Very quick [e.g., intra-op PTH] Minimal blood or serum required

20. Mechanisms of Action Activation of cyclic AMP system of cells Need hormone receptor [key and lock] Cyclic AMP forms as an intracellular hormonal mediator [aka as “second messenger”] ACTH, TSH, FSH, LH, ADH, PTH, glucagon Effects can be instantaneous

22. 2nd mechanism of action Activation of genes in target cells, causing formation of intracellular proteins Steroid hormone enters cytoplasm and binds to receptor proteins Enters nucleus to activate genes to form messenger RNA m-RNA promotes new proteins to be made Delayed effect of mins [aldosterone] to days

24. Transport of Hormones Biologic effect due to free hormones Binding globulins – “the buses” –Thyroid Binding Globulin [TBG] –Sex-hormone Binding Globulin [SHBG] –Cortisol Binding Globulin [CBG] –Produced in liver What is assay measuring? “Total” [I.e., bound] vs. “Free”

25. Sandwich-type assays refer to: A. Dialysis method B. Ham and cheese C. Two antibodies D. Live cellular responses

26. Control of Hormonal System Tendency of each gland is to oversecrete Need method to prevent oversecretion Need method to stimulate production if undersecreting KEY is Negative Feedback Some exceptions [e.g., prolactotrophs and dopaminergic inhibitory fibers]

29. Key Points Hormones effect metabolism all tissues Instantaneous vs. prolonged effects Free hormones biologically active Negative feedback is KEY to normal homeostasis