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Endocrine Physiology Bob Bing-You, MD, MEd, MBA Medical Director Maine Center for Endocrinology 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 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 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 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] org] with confused thoughts, concepts, etc.

Major Areas • • • Thyroid gland Adrenal gland function, steroid Rx Diabetes: glucose 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 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 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 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 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 More Hormones • Posterior pituitary: antidiuretic hormone [ADH] • Adrenal – Aldosterone – Glucocorticoids [cortisol] – Testosterone, estrogen – catecholamines

Even More Hormones! • Thyroid hormones: thyroxine [T 4], triiodothyronine [T 3] • Pancreatic: Even More Hormones! • Thyroid hormones: thyroxine [T 4], triiodothyronine [T 3] • Pancreatic: insulin, glucagon • Parathyroid: parathyroid hormone [PTH]

Chemistry of Hormones • Two types – Proteins or derivatives of proteins or amino 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. 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 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 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 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

2 nd mechanism of action • Activation of genes in target cells, causing formation 2 nd 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 – 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. 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 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 Key Points • • Hormones effect metabolism all tissues Instantaneous vs. prolonged effects Free hormones biologically active Negative feedback is KEY to normal homeostasis