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Some Definitions I

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. Some Definitions II.

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Some Definitions I

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  1. 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

  2. Some Definitions II • 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)

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

  4. 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 “Classic” Endocrine Glands

  5. 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 “Non-classic” Endocrine Glands

  6. 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)

  7. Amine

  8. Thyroid Hormones

  9. Peptides & Steroids Hormones

  10. 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

  11. 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)

  12. Vescicular & Non-vesc. Secretion

  13. 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

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

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

  16. G-protein coupled Receptor

  17. Nuclear Receptor

  18. Effects of Hormone Action • Agonist • Weak agonist (partial agonist) • Antagonist

  19. 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

  20. The feedbacks controller controller a b a b target target

  21. 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

  22. 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

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