Some Definitions I Endocrine: glandular secretion of substances inside the body Exocrine: glandular secretion of substances outside the body (sweat gland, liver, pancreas) The endocrine system uses hormones to convey information through the bloodstream

Hormone: a substance released by an endocrine gland and transported through the bloodstream to another tissue (target) where it exerts its function (stimulatory or inhibitory) Autocrine: the hormone acts on the cell that has produced it(insulin) Paracrine: the hormone acts locally on nearby cells (sex steroids in the ovary) Some Definitions II

The endocrine glands Several glands located in different areas of the body Ductless (do not have a duct system) Richly vascularized

“Classic” Endocrine Glands Anterior Hypophysis ACTH, TSH, LH, FSH, GH, PRL Posterior Hypophysis Oxytocin and ADH Thyroid T4, T3 and calcitonin Parathyroid PTH Adrenal Cortex Aldosteron, Cortisol, DHEA et al. Adrenal Medulla Epinephrine and Norepinephrine Testis Testosterone, Inhibin Ovary Estradiol, androgens Pancreatic Islets Insulin, glucagon, somatostatin, etc Placenta hCG, hPL, estradiol, progesterone

“Non-classic” Endocrine Glands Brain CRH, TRH, GnRH, dopamine, GHRH, somatostatin Heart Atrial natriuretic peptide Kidney Renin, 1,25-Vit. D, erythropoietin Liver Insulin-like growth factor-1 Stomach Gastrin Small intestine Many regulatory peptides

Chemical Nature of Hormones Derived from one amino acid (tyrosine): amine: dopamine, norepinephrine, epinephrine thyroid hormones: T4 and T3 Polypeptides: some are small (TRH is 3 AA) some are big (GH is ~200 AA) Steroid hormones (derived from cholesterol): with intact steroid nucleus (gonadal and adrenal) with broken steroid nucleus (vitamin D)

Amine

Thyroid Hormones

Peptides & Steroids Hormones

Functions of Hormones Reproduction and Sex Ex: LH, FSH, PRL, E2 and T Growth Ex: GH, insulin-like growth factors Maintenance of water, electrolyte & blood pressure: ADH water Aldosterone Na and K PTH, Vit. D, calcitonin calcium and phosphate Epi. & norepinephrine blood pressure Regulation of energy availability: Insulin, glucagon and cortisol glucose Thyroid hormones basal metabolism

Hormone Synthesis & Release Vescicular versus nonvescicular The basal secretion is pulsatile (not continuous) The secretory episodes may have different periodicity: Circa-horal Circa-dian Circa-trigintan Circa-annual (seasonal)

Vescicular & Non-vesc. Secretion

Hormone Transport Amine and Polypetide hormones usually circulate free in the bloodstream Exception: insulin-like growth factors Steroids and thyroid hormones circulate bound to transport proteins: Specific: TBG for T4 and T3, SHBG for T and E2, CBG for cortisol Non-specific: albumin and pre-albumin

Hormone Transport Binding influences clearance Only the free hormone is “active” Only the free hormone dictates the feedback

Mechanisms of Hormone Action Cell surface receptors: Seven transmembrane receptors (G linked) Growth factor receptors Nuclear receptors: Steroids receptor family Thyroid hormones receptor family

G-protein coupled Receptor

Nuclear Receptor

Effects of Hormone Action Agonist Weak agonist (partial agonist) Antagonist

Hormone Metabolism & Clearance Only a small fraction of circulating hormone is taken up by the target tissue The bulk of clearance is done by liver and kidneys Many kinds of enzymatic reactions: hydrolysis, oxidation, hydroxylation, methylation, decarboxylation, sulfation, glucuronidation Only a small fraction is excreted intact in urine or feces

The feedbacks controller target controller target abab

The negative feedback Long loop: inhibition of pituitary secretion by hormones released by the target organs Short loop: inhibition of hypothalamic secretion by pituitary hormones Ultrashort loop: inhibition of hypothalamic secretion by hypothalamic hormones

Mechanisms of Endocrine Disease Hypofuction (hormone deficiency) Hyperfunction (hormone excess) Hormone resistance: the hormone itself is abnormal the receptor is “blocked” by antibodies the receptor itself is abnormal the post-receptor pathway is abnormal