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Nature of hormones
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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
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Endocrine factors Autocrine factors Paracrine 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
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GnRH Hypothalamus FSH LH Estradiol Pituitary gland Ovary
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Granulosa cells Basement membrane Antrum Oocyte Theca externa Theca interna
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Granulosa cells (GC) Theca cells (TC) Basement membrane
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General characteristics of hormones
Very low in concentrations Ppb (ng/ml) or ppt (pg/ml) Very specific receptor One hormone, one receptor
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Chemical nature of hormones
Classes Lipids Steroids Eicosanoids Proteins Short polypeptides Large proteins Chemical modification through glycosylation Amino acid derivatives
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Steroid hormones Derivative of cholesterol Large molecule
Hydrocarbon ring Highly hydrophobic Source Diet De Novo synthesis Found in cell membrane
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Cholesterol and its derivatives
Vitamin D Bile acid Lipid digestion Steroid hormones Sex steroids Adrenal steroild All cholesterol derivatives contain sterol ring
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Steroid hormones Origins Adrenal Gonads (testis and ovaries)
Mineralocorticoids Affect mineral homeostasis Glucocorticoids Affect glucose metabolism and immune function Gonads (testis and ovaries) Estrogens Progestins/progestagens Androgens
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Eicosanoids Metabolites of 12-C fatty acid Prostaglandins
Arachidonic acid Prostaglandins Produced by numerous tissues and organs Originally isolated from prostate gland secretion Inflammatory reaction Reproduction Thromboxanes, leukotriens, and prostacyclins
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Protein hormones Short chain of amino acids Neurohormones GnRH (10)
Oxytocin (9) TRH (3)
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Protein hormones Large polypeptides Linear chain Subunits
Linked by disulfide bridge(s) 3-D structure Critical for interaction with receptor
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Chemical modification
Glycosylation Common in gonadotropins (LH, FSH, hCG, eCG) Sulfation Acetylation
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Protein hormones Isoform and variants Amino acid substitution
Gene duplication
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Amino acid metabolites
Tyrosine metabolites Thyroid hormones Thyroxine Triiodothyronine Adrenal medulla Epinephrine Norepinephrine Dopamine Often used as neurotransmitters
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Endocrine glands Composition Permanent or transient
Parenchyma (mass of cells) Secretory cells Blood vessels Highly vasucualized No ducts Permanent or transient Pituitary, adrenal, pancreas etc Ovarian follicle and corpus luteum
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Cells that produce hormone
Specialized secretory cells Usually one type of cells produce one hormone Neurons Hypothalamus Posterior pituitary Adrenal medulla
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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
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Metabolism Cholesterol (steroids) Tyrosine Smooth ER Mitochondria
Thyroid follicular cells (thyroid hormones) Thyroglobulin Adrenal medulla Nerve terminals
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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
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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
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Steroids Thyroid hormones 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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