nature of hormones
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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 - PowerPoint PPT PresentationTRANSCRIPT
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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– 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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LH FSH
Estradiol
Hypothalamus
Pituitarygland
GnRH
Ovary
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Antrum
Granulosa cells
Theca internaTheca externa
Basementmembrane
Oocyte
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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
• 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
• Mineralocorticoids– Affect mineral homeostasis
• Glucocorticoids– Affect glucose metabolism and immune function
– Gonads (testis and ovaries)• Estrogens• Progestins/progestagens• Androgens
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www.endotext.org/male/male1/figures1/figure13.gif
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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
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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– 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)
• Smooth ER• Mitochondria
– Tyrosine• 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– 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