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Transcript
Endocrine Physiology Bob Bing-You, MD, MEd, MBA Medical Director Maine Center for Endocrinology 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. Learning Objectives • Explain normal feedback mechanisms for normal endocrine function • Describe abnormal pathophysiologic states • Define treatment approaches for such states Ground Rules • • • • Case-based, common examples Feel to ask questions anytime Take a few breaks for Q and A Call or e-mail [[email protected]] with confused thoughts, concepts, etc. Major Areas • • • • • • Thyroid gland Adrenal gland function, steroid Rx Diabetes: glucose monitoring, insulin Rx Calcium homeostasis, vitamin D Pheochromocytoma Diabetes insipidus 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 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 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 Major Hormones • Anterior pituitary – – – – – – Growth hormone Adrenocorticotropin [ACTH] Thyroid-stimulating hormone [TSH] Follicle-stimulating hormone [FSH] Luteinizing hormone [LH] Prolactin [PRL] More Hormones • Posterior pituitary: antidiuretic hormone [ADH] • Adrenal – – – – Aldosterone Glucocorticoids [cortisol] Testosterone, estrogen catecholamines Even More Hormones! • Thyroid hormones: thyroxine [T4], triiodothyronine [T3] • Pancreatic: insulin, glucagon • Parathyroid: parathyroid hormone [PTH] 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., onemillionth of a milligram] • Bioassay vs. radioimmunoassay What describes hormones effecting other local cells? • • • • A. Paracrine B. Endocrine C. Autocrine D. None of the above. Bioassay • Animal cell tissue system • Plasma or some extract added to see effect • E.g., testosterone Immunoassay • Sandwich-type • Very quick [e.g., intra-op PTH] • Minimal blood or serum required 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 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 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” Sandwich-type assays refer to: • • • • A. Dialysis method B. Ham and cheese C. Two antibodies D. Live cellular responses 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] Key Points • • • • Hormones effect metabolism all tissues Instantaneous vs. prolonged effects Free hormones biologically active Negative feedback is KEY to normal homeostasis