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Androgen and Estrogen Metabolism
描述
This pathway describes the inactivation and catabolism of male (androgen) and female (estrogen) hormones. Many steroid hormones are transformed by sulfatases, dehydrogenases and glucuronide transferases to enhance their solubility and to facilitate their elimination. Inactivation refers to the metabolic conversion of a biologically active compound into an inactive one. Peripheral inactivation (e.g. by liver enzymes) is required to ensure steady-state levels of plasma androgens and estrogens. Specifically, if an androgen or estrogen is to act as a " chemical signal ", its half-life in the circulation must be limited, so that any change in secretion rate is immediately reflected by a change in its plasma concentration. But hormone inactivation can also occur in target tissues, notably after the hormone has triggered the relevant biological effects in order to ensure termination of hormone action. The main site of peripheral androgen/estrogen inactivation and catabolism is the liver, but some catabolic activity also occurs in the kidneys. Inactive androgens and estrogens are mainly eliminated as urinary (mostly conjugated) metabolites. This elimination requires conversion to hydrophilic compounds in order to ensure their solubility in biological fluids at rather high concentrations. Depending on the structure of the starting steroid there may be: 1) Reduction of a double bond at C-4 and reduction of an oxo(keto) group at C-3 to a secondary alcoholic group; 2) Reduction of an oxo group at C-20 to a secondary alcoholic group; 3) Oxidation of a 17?-hydroxyl group; 4) Further hydroxylations at various positions of the steroid nucleus (e.g. 7-hydroxylation of 5a-reduced androgens) or 5) Conjugation (sulphate and/or glucuronide derivatives).