1. ANPS Anatomy & Physiology Endocrinology II

2. Hypothalamus CRH corticotropin releasing hormone TRH thyrotropin releasing hormone GnRH gonadotropin releasing hormone GHRH GH releasing hormone GIH (somatostatin) GH inhibitory hormone PRL prolactin releasing hormone Gonadotrophs (LH / FSH cells) Corticotrophs (ACTH) Thyrotrophs (TSH) Lactotrophs (PRL) Adrenal gland Thyroid gland Ovary, Testis Mammary tissue Anterior pituitary cell types Somatotrophs (GH) Liver, Muscle, fat

3. Growth Hormone (GH): primary hormone in human growth secreted throughout life but declines with age produced by anterior pituitary somatotroph cells targets muscle, liver and adipose (fat) tissues GH has direct and indirect effects indirect effects mediated by liver insulin-like growth factors (IGFs) actions on organs/bones stimulated by hypothalamic GHRH release into portal system inhibited by somatostatin (GIH) and feedback mechanisms stimulates linear growth increases organ growth, increases muscle mass generates fuel – stimulates lipolysis (decreases fat depots) – increases liver glucose production – decreases tissue glucose storage proliferation/survival effects Somatotrophs Muscle, Liver, Fat (adipose), Bone (indirect) Hypothalamus GHRH GH releasing hormone GIH (somatostatin) GH inhibitory hormone GHRH (GH)

4. Target tissues (muscle, liver, fat) GH release G protein coupled receptors Hypothalamus Anterior pituitary somatotrophs GH GHRH (+) (GIH) Somatostatin (-)

5. Growth Hormone (GH)

6. Hypothalamus Anterior pituitary GH Adipose tissue (GH receptors) Liver (GH receptors) Muscle (GH receptors) GHRH (+) Somatostatin (-) (GPCR) Somatic cell growth (IGF receptors) Insulin-like growth factors (IGFs) Bone chondrocyte/osteoblast function (IGF receptors)

7. Hypothalamus Anterior pituitary GH Adipose tissue Lipolysis glucose uptake Liver Gluconeogenesis Muscle Amino acid uptake protein synthesis glucose uptake GHRH (+) Somatostatin (-) lean body mass free fatty acids blood glucose (-) IGFs Somatic cell growth organ/tissue size and function Bone chondrocyte/osteoblast function linear growth IGFs

8. Growth Hormone: net effects Direct effects: Adipose tissue stimulates lipolysis, increasing blood free fatty acid  fuel (muscle) decreases glucose uptake Liver increases gluconeogenesis increases IGF production (see indirect effects below) Muscle stimulates amino acid uptake/protein synthesis, increasing lean body mass decreases glucose uptake (net effect of glucose on all 3 tissues is increased blood glucose levels  fuel for brain and other tissues) Indirect effects (from IGF signaling): increase organ size and function (increased cell survival/proliferation/differentiation) stimulate bone chondrocyte function at epiphyseal plates to enhance linear growth increase in lean muscle mass may be predominantly an IGF effect

9. Gigantism v acromegaly

10. Hypothalamus CRH corticotropin releasing hormone TRH thyrotropin releasing hormone GnRH gonadotropin releasing hormone GHRH GH releasing hormone GIH (somatostatin) GH inhibitory hormone PRL prolactin releasing hormone Gonadotrophs (LH / FSH cells) Corticotrophs (ACTH) Thyrotrophs (TSH) Lactotrophs (PRL) Adrenal gland Thyroid gland Ovary, Testis Mammary tissue Anterior pituitary cell types Somatotrophs (GH) Liver, Muscle, fat

12. Thyroid follicle structure: colloid follicular cells

13. Thyroid stimulating hormone (TSH): Hypothalamus (TRH) Ant. pituitary thyrotrophs TSH Thyroid follicular cells Thyroid hormone thyroxine/triiodothyronine (T4/T3) regulated by hypothalamic TRH (thyrotropin releasing hormone) TRH binds thyrotroph GPCRs for TSH release TSH binds thyroid cells GPCRs for T3/T4 synthesis/release T3/T4 bind to cytosolic receptors in target cells Thyroid hormones: regulates basal metabolic rate (BMR) key in bone and nervous system development increases gut carbohydrate absorption decreases circulating cholesterol stimulates lipolysis increased protein breakdown (resulting in weight loss if food is not increased) facilitates autonomic function; inotropic and chronotropic

14. Thyroid follicle structure: colloid follicular cells

15. Thyroid hormone (T3/T4) biosynthesis: dietary iodide and thyroglobulin (TG) are key substrates for T3/T4 synthesis synthesis occurs on TG backbone in colloid final T3/T4 products formed in cells T3 is 4x more active; T4 is 20x more abundant T4 is converted to T3 by deiodinases in tissues Long T3/T4 feedback to pituitary/hypothalamus colloid

16. Thyroid Stimulating Hormone (TSH)

17. Cellular effects: consume more O2, burn more fuel, calorigenic increase BMR (energy prod/unit time (cal)) “make things work – better” Physiological effects: contributes to bone, nervous system, tissue growth and development increase ventilation, cardiac output, renal function increase BMR – need more fuel; increase food intake, increase lipolysis (decrease fat – release FFA), increase carbohydrate absorption from gut; decrease muscle mass is food not increased. Cellular effects Physiological functions

18. Thyroid Stimulating Hormone (TSH)

19. Hyperthyroidism (too much thyroid hormone): people are “hyper”, BMR 10 – 100% above normal nervousness, fine tremor at fingers weightloss, hyperphagia increase pulse pressure, heat intolerant, sweating Grave’s disease – autoimmune antibodies activate TSH receptors resulting in increased T3/T4 production (low circulating TSH) treatment – radioactive iodine, propythiouracil (PTU), surgery Hypothyroidism (too little thyroid hormone): BMR falls to 40% of normal “can’t think”, poor memory lethargic, listless skin dry, poor cold tolerance Hashimoto’s disease – autoimmune antibodies destroy thyroid gland (high levels of circulating TSH in blood) hypothyroid children develop poorly (dwarfed) and can show mental retardation (cretinism – rare) treatment – thyroid hormone supplements

20. Parathyroid glands Calcium homeostasis Three regulators: parathyroid hormone (PTH) vitamin D calcitonin Three integrated sites of action: bone – largest reservoir of body calcium GI calcium absorption kidney calcium excretion Calcium importance: bone maintenance nervous system signaling muscle contraction, skeletal, smooth, cardiac blood clotting others.......

21. Parathyroid hormone (PTH) produced by parathyroid gland activates G protein coupled receptors on target tissues (bone, kidney) Vitamin D not one but class of compounds synthesis in 3 tissues (skin, liver, kidney) PTH important in final synthesis of active vit. D in kidney PTH Skin Liver Kidney Active form 1,25-(OH) 2 D = calcitriol hv = calcidiol

22. Body calcium homeostasis free (ionized) calcium is active (50% free - 50% bound) PTH and blood calcium levels are tightly balanced drop in blood calcium leads to increased PTH release via G protein coupled Ca sensing receptors in gland PTH does 3 things: PTH increases bone release of free calcium (slow) PTH increases recovery of calcium from kidney (fast) PTH stimulates kidney calcitriol (1,25-(OH) 2 D) synthesis Calcitriol binds to steroid-type receptors in gut to stimulate calcium absorption from food

23. 25(OH)D = calcidiol 1,25(OH)2D = calcitriol *(active)

24. Calcitonin peptide produced by thyroid C cells decreases blood calcium; opposite effects of PTH and vit. D blood calcium so tightly coupled with PTH/vit.D that calcitonin is more important during development than in adults

26. Hypothalamus CRH corticotropin releasing hormone TRH thyrotropin releasing hormone GnRH gonadotropin releasing hormone GHRH GH releasing hormone GIH (somatostatin) GH inhibitory hormone PRL prolactin releasing hormone Gonadotrophs (LH / FSH cells) CorticotrophsThyrotrophsSomatotrophsLactotrophs Adrenal gland Thyroid gland Ovary, Testis Liver, Muscle, fat Mammary tissue Anterior pituitary cell types