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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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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
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
GnRH Hypothalamus FSH LH Estradiol Pituitary gland Ovary
Granulosa cells Basement membrane Antrum Oocyte Theca externa Theca interna
Granulosa cells (GC) Theca cells (TC) Basement membrane
General characteristics of hormones • Very low in concentrations • Ppb (ng/ml) or ppt (pg/ml) • Very specific receptor • One hormone, one receptor
Chemical nature of hormones • Classes • Lipids • Steroids • Eicosanoids • Proteins • Short polypeptides • Large proteins • Chemical modification through glycosylation • Amino acid derivatives
Steroid hormones • Derivative of cholesterol • Large molecule • Hydrocarbon ring • Highly hydrophobic • Source • Diet • De Novo synthesis • Found in cell membrane
Cholesterol and its derivatives • Derivatives • Vitamin D • Bile acid • Lipid digestion • Steroid hormones • Sex steroids • Adrenal steroild • All cholesterol derivatives contain sterol ring
Steroid hormones • Origins • Adrenal • Mineralocorticoids • Affect mineral homeostasis • Glucocorticoids • Affect glucose metabolism and immune function • Gonads (testis and ovaries) • Estrogens • Progestins/progestagens • Androgens
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
Protein hormones • Short chain of amino acids • Neurohormones • GnRH (10) • Oxytocin (9) • TRH (3)
Protein hormones • Large polypeptides • Linear chain • Subunits • Linked by disulfide bridge(s) • 3-D structure • Critical for interaction with receptor
Chemical modification • Glycosylation • Common in gonadotropins (LH, FSH, hCG, eCG) • Sulfation • Acetylation
Protein hormones • Isoform and variants • Amino acid substitution • Gene duplication
Amino acid metabolites • Tyrosine metabolites • Thyroid hormones • Thyroxine • Triiodothyronine • Adrenal medulla • Epinephrine • Norepinephrine • Dopamine • Often used as neurotransmitters
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
Cells that produce hormone • Specialized secretory cells • Usually one type of cells produce one hormone • Neurons • Hypothalamus • Posterior pituitary • Adrenal medulla
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
Metabolism • Cholesterol (steroids) • Smooth ER • Mitochondria • Tyrosine • Thyroid follicular cells (thyroid hormones) • Thyroglobulin • Adrenal medulla • Nerve terminals
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
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
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