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Nature of hormones

Nature of hormones. What is a hormone?. Hormone Greek “I excite” or “I arouse” Classical definition Chemical messenger released by one type of cells and carried in the bloodstream to act on specific target cells Modern definition

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Nature of hormones

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  1. Nature of hormones

  2. What is a hormone? • Hormone • Greek “I excite” or “I arouse” • Classical definition • Chemical messenger released by one type of cells and carried in the bloodstream to act on specific target cells • Modern definition • Includes factors produced and used locally without entering the blood stream

  3. Endocrine factors • Released and carried in the blood • Classical hormones • Autocrine factors • Released and used by the same cells • Paracrine factors • Affect function of neighboring cells without entering the blood stream • Interstitial fluid

  4. GnRH Hypothalamus FSH LH Estradiol Pituitary gland Ovary

  5. Granulosa cells Basement membrane Antrum Oocyte Theca externa Theca interna

  6. Granulosa cells (GC) Theca cells (TC) Basement membrane

  7. General characteristics of hormones • Very low in concentrations • Ppb (ng/ml) or ppt (pg/ml) • Very specific receptor • One hormone, one receptor

  8. Chemical nature of hormones • Classes • Lipids • Steroids • Eicosanoids • Proteins • Short polypeptides • Large proteins • Chemical modification through glycosylation • Amino acid derivatives

  9. Steroid hormones • Derivative of cholesterol • Large molecule • Hydrocarbon ring • Highly hydrophobic • Source • Diet • De Novo synthesis • Found in cell membrane

  10. Cholesterol and its derivatives • Derivatives • Vitamin D • Bile acid • Lipid digestion • Steroid hormones • Sex steroids • Adrenal steroild • All cholesterol derivatives contain sterol ring

  11. Steroid hormones • Origins • Adrenal • Mineralocorticoids • Affect mineral homeostasis • Glucocorticoids • Affect glucose metabolism and immune function • Gonads (testis and ovaries) • Estrogens • Progestins/progestagens • Androgens

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  13. Eicosanoids • Metabolites of 12-C fatty acid • Arachidonic acid • Prostaglandins • Produced by numerous tissues and organs • Originally isolated from prostate gland secretion • Inflammatory reaction • Reproduction • Thromboxanes, leukotriens, and prostacyclins

  14. Protein hormones • Short chain of amino acids • Neurohormones • GnRH (10) • Oxytocin (9) • TRH (3)

  15. Protein hormones • Large polypeptides • Linear chain • Subunits • Linked by disulfide bridge(s) • 3-D structure • Critical for interaction with receptor

  16. Chemical modification • Glycosylation • Common in gonadotropins (LH, FSH, hCG, eCG) • Sulfation • Acetylation

  17. Protein hormones • Isoform and variants • Amino acid substitution • Gene duplication

  18. Amino acid metabolites • Tyrosine metabolites • Thyroid hormones • Thyroxine • Triiodothyronine • Adrenal medulla • Epinephrine • Norepinephrine • Dopamine • Often used as neurotransmitters

  19. Endocrine glands • Composition • Parenchyma (mass of cells) • Secretory cells • Blood vessels • Highly vasucualized • No ducts • Permanent or transient • Pituitary, adrenal, pancreas etc • Ovarian follicle and corpus luteum

  20. Cells that produce hormone • Specialized secretory cells • Usually one type of cells produce one hormone • Neurons • Hypothalamus • Posterior pituitary • Adrenal medulla

  21. Hormone synthesis • Protein hormones • Transcription • Translation • Physical/chemical modification • Cleaving of long amino acid chain (preprohormones) to generate small peptide hormones (GnRH, oxytocin, TRH) • Interaction and linking of subunits • 3-D structure

  22. Metabolism • Cholesterol (steroids) • Smooth ER • Mitochondria • Tyrosine • Thyroid follicular cells (thyroid hormones) • Thyroglobulin • Adrenal medulla • Nerve terminals

  23. Control of synthesis and secretion • Neural inputs • Brain • Hypothalamus • Hormonal stimulation/inhibition • Releasing factors/hormones • Inhibitory factors • Feedback system • Metabolic status • Stress • Blood concentrations of substances • Ca • Glucose • Water

  24. Hormones in circulation • Peptides and some protein hormones (i.e. insulin) • Very short half-life • Degraded by proteolytic enzymes • Large protein hormones • Longer half-life

  25. Steroids • Water-insoluble • Bound to binding globulins (SHBG or CBG) and albumin • Some steroids exist as free form • Short half-life • Thyroid hormones • Thyroxine-binding globulin (TBG) • Transthyretin

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