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Circulation, action, and inactivation of hormones
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Many hormones are transported to their site of action by carrier proteins, where they exert their action and are then inactivated by further metabolism
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Table 37-1. The chemical derivation of hormones.
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Chemical derivation of hormones
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Derived from amino acidsView drug information
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Amino acid derivativescatecholamines, serotonin, thyroxine
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TripeptidesTRH
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Small peptidesVP (ADH), somatostatin
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Intermediate-size peptidesinsulin, parathyroid hormone
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Complex polypeptides and glycoproteinsgonadotropins, TSH
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Derived from lipid precursors
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Cholesterol derivativescortisol, testosteroneView drug information, estradiolView drug information, vitamin D
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Fatty acid derivativesprostaglandins, leukotrienes
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Phospholipid derivativeplatelet-activating factor
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Derived from other chemicals
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PurinesadenosineView drug information
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Gasesnitric oxideView drug information
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AVP/ADH, arginine vasopressinView drug information or antidiuretic hormone; TRH, thyrotropinView drug information releasing hormone; TSH, thyroid stimulating hormone.
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HORMONE IMMUNOASSAY - A BILLION DOLLAR BUSINESS
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Immunoassay is the most widely applied technique for measuring hormones in biological samples. Antibodies are produced that bind to antigenic sites on the hormone. Ideally, this antibody should possess both high specificity and affinity for the hormone of interest, e.g. the β-subunit of glycoprotein hormones.
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In the first immunoassays, the antibodies were produced in the serum of animal species (e.g. rabbit or sheep) that had been immunized with human hormone preparations. Such antisera contained a range of different antibodies (polyclonal) capable of binding to different sites on the hormone antigen. However, antibody specificity and titer varied with the animal and duration of the immune response. Today most immunoassays employ monoclonal antibodies, which are produced by fusion of spleen cells from an immunized mouse with a mouse myeloma cell line. Hybridoma cells may be cloned to produce a cell line that secretes a single antibody species for an indefinite period of time.
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Many commercial producers have designed proprietary methods for quantifying the hormone-antibody interaction. One of the most widely used formats is the two-site (sandwich) immunometric or ELISA assay assay outlined in Figure 37.2. This assay employs two antibodies binding to different epitopes on the hormone, one of which is modified to be capable of generating an optical signal. Spectrophotometric, fluorometric, luminescence and radiochemical reporter systems are in common use.
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Within the circulation, small or hydrophobic hormones are transported bound to carrier proteins. For example, thyroxine and cortisol are transported on specific plasma binding globulins such as thyroid-binding globulin (TBG) and cortisol-binding globulins (CBG). The transport proteins extend the biological half-life and increase the plasma concentration of the smaller hormones, which would otherwise be eliminated rapidly in the liver or kidney. The rate of clearance of different hormones varies enormously, from a few minutes (insulin), to hours (steroids), to days (thyroxine). At the cellular level, hormones exert their actions through a wide range of signal transduction mechanisms (Chapter 38). Hormone inactivation usually occurs by further metabolism (e.g. proteolysis, hydroxylation, and conjugation), followed by excretion of the metabolites. Measurement of urinary concentrations of hormone metabolites can be used to diagnose pregnancy or disease.
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