Formation, metabolism, and physiologic importance of catecholestrogens.
The metabolism of natural and synthetic estrogens is governed primarily by hydroxylations, leading to polyhydroxylated derivatives of the steroid molecule. In mammals aromatic hydroxylation is most prominent quantitatively. The 2- and 4-hydroxyestrogens (catecholestrogens) formed are secreted not only in high amounts in urine but are also present in significant quantities in different organs, such as the liver, pituitary gland, and hypothalamus. This A ring hydroxylation of primary estrogens is affected by peroxidases, tyrosinases, and unspecific monooxygenases by mechanisms still not completely understood. The activity of the aromatic hydroxylases is regulated not only with respect to the overall extent but also to the relative rate of hydroxylation at C-atoms 2 and 4. The metabolism of catecholestrogens may be divided into reversible and irreversible reactions, of which the reaction with the catechol-O-methyltransferase, and thereby the interaction with catecholamines, the conjugation, and the thioether formation are the most prominent. Low- and high-affinity binding is operative in binding to plasma proteins and receptors. Finally, irreversible binding to cellular macromolecules, such as proteins and deoxyribonucleic acid, and the oncogenic potential of natural and synthetic catecholestrogens are discussed.
Ball
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Klinische Endokrinologie, Medizinische Universität zu Lübeck, West Germany.
Knuppen
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D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D002393:Estrogens, Catechol / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D008099:Liver / Q000378:metabolism; D011506:Proteins / Q000378:metabolism
D002395:Catecholamines; D004967:Estrogens; D002393:Estrogens, Catechol; D011506:Proteins; D004958:Estradiol; D004247:DNA