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Endocrinology & Metabolism

Endocrinology & Metabolism. Introduction EM001, 002, 003. Introduction. Robert Shiu, Ph.D. (Notes prepared by Janice Dodd, Ph.D.) Department of Physiology. Agenda. Role of the endocrine system Structure and function of hormones How hormones are measured. Chapter 1. Endocrine system

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Endocrinology & Metabolism

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  1. Endocrinology & Metabolism Introduction EM001, 002, 003

  2. Introduction Robert Shiu, Ph.D. (Notes prepared by Janice Dodd, Ph.D.) Department of Physiology

  3. Agenda • Role of the endocrine system • Structure and function of hormones • How hormones are measured

  4. Chapter 1 • Endocrine system • overview of endocrine effects • endocrine glands, target cells • Hormones • synthesis, structure, storage, secretion, and transport

  5. Overview • Endocrine system controls • Development and Growth • Energy regulation (storage & mobilization) • Internal homeostasis (fluids, ions) • Reproduction (sex, pregnancy, lactation)

  6. Endocrine action • Endocrine system controls physiology via chemical signals from one part of the body to another • Target cell undergoes a biological response

  7. Vocabulary • Endocrine - borne via bloodstream • Paracrine - acting in local environment • Autocrine - acting on secreting cell

  8. more Vocabulary • Neurocine - neural cells that release chemical signals into the bloodstream

  9. Major Endocrine Glands • Hypothalamus • Anterior pituitary • Posterior pituitary • Pineal • Thyroid • Parathyroids • Adrenal medulla • Adrenal cortex • Pancreas • Ovaries • Testes • Placenta

  10. Functional classifications • Releasing hormones • From hypothalamus to act on pituitary • Stimulating (or tropic) hormones • From pituitary to act on another endocrine gland • Non-tropic hormones • From an endocrine gland to target cells

  11. Releasing, Stimulating and Non-tropic Hormones • Hypothalamus releases Thyrotropin Releasing Hormone (TRH) • Anterior pituitary releases Thyroid Stimulating Hormone (TSH) • Thyroid releases Thyroid Hormone (T3 and T4) • Target cells respond • Feedback (stay tuned)

  12. Endocrine target cells • Target cells respond to hormones via specific receptors • All cells respond to multiple hormones • Receptors may be at the cell surface or intracellular

  13. Chemical Classification of Hormones • Amino hormones -derived from tyrosine • Peptide and protein hormones - encoded in genes • Steroid hormones • derived from cholesterol • Eicosanoid hormones • derived from fatty acids (arachadonic acid)

  14. Amino Hormones • Derived from the amino acid tyrosine • Includes the catecholamines epiniephrine and norepinephrine from adrenal medulla • Includes thyroid hormones thyroxine (T4) and trioiodothyronine (T3) from thryoid

  15. Thyroid Hormones • Thyroid pro-hormone is stored as thyroglobulin as an extracellular colloid • T3 and T4 can cross lipid membranes readily (secretion and uptake) • T3 and T4 are small, hydrophobic and circulate bound to Thyroxine-binding globulin (TBG)

  16. Protein & Polypeptide Hormones Insulin Synthesis • Transcribed from genes • Translated in rough ER, processed in Golgi, stored in secretory vesicles • May undergo one or more post-translational modifications including cleavage, glycosylation, disulfide bridging

  17. Subunit Hormones • Several tropic hormones made by the anterior pituitary are glycoproteins that share a common alpha subunit • Human chorionic gonadotropin (hCG) from the placenta also has the same alpha subunit • Specificity is achieved through beta subunit

  18. Protein Hormones • Protein and polypeptide hormones (including glycoprotein subunit hormones) are stored in secretory granules and released on stimulation • Ca++ dependent event – exocytosis • Hydrophilic - cannot freely cross membranes

  19. Steroid Hormones • Not encoded in genes, but derived from cholesterol through enzymatic reactions • Cholesterol is converted to pregnenolone • Pregnenolone moves between mitochondria and ER and is precursor to all steroids • Includes Glucocorticoids, Mineralocorticoids, Androgens, Estrogens and Progestins

  20. Enzymes in Steroid Biosynthesis • Side-chain cleavage enzyme; desmolase (CYP11A1) • 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) • 17 alpha-hydroxylase/17,20 lyase (CYP17) • 21-hydroxylase (CYP21A2) • 11 beta-hydroxylase (CYP11B1) • Aldosterone synthase (CYP11B2) • Aromatase (CYP19) • Mutation or failure of any of these genes can lead endocrine disease • Eg. Aromatase (CYP19) block will prevent estrogen synthesis

  21. Steroid Hormones • Steroids are lipophilic molecules that freely cross membranes • Steroids are not stored in endocrine glands but are released as made • Steroids travel in the blood associated with Steroid-binding Globulins (SBGs)

  22. Eicosanoid hormones • Small lipid molecules • Most abundant precursor is arachadonic acid • Includes prostaglandins, prostacyclins, leukotrienes, thromboxanes • Very short half-lives

  23. Terminology Tyranny • Hormones are often named after the first site of extraction or first demonstrated biological effect • Names are historical records - don’t limit your thinking! • Eg. Prostaglandins

  24. Summary • Overview of endocrine effects • Major endocrine glands • Chemical classification of hormones • Functional classification

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