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Estradiol metabolism


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Estradiol metabolism

Estradiol metabolism.

Endogenous and exogenous estrogens undergo oxidative metabolism by hepatic microsomalcytochrome P-450. Aromatic hydroxylation at either the C2 or C4 position is a major routeof Estradiol metabolism in humans and other mammals, although there is less4-hydroxylation than 2-hydroxylation. 

Several cytochrome P450 isoforms including Cytochrome P450, family 2, subfamily C,polypeptides 8 ( CYP2C8 ) [1] and 9 ( CYP2C9 ) [1], Cytochrome P450, family 3, subfamily A, polypeptides 4 ( CYP3A4 )[2] and 5 ( CYP3A5 ) [1], Cytochrome P450, family 2,subfamily D, polypeptide 6 ( CYP2D6 ) [1], Cytochrome P450, family 1,subfamily A, polypeptides 1 ( CYP1A1 ) [2] and 2 ( CYP1A2 )[2], Cytochrome P450, family 1, subfamily B, polypeptide 1 ( CYP1B1 )[3] and Cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19 ) [1] were shown to catalyze hydroxylation ofEstradiol to 2-Hydroxyestradiol or/and 4-Hydroxyestradiol.Furthermore, Catechol-O-methyltransferase ( COMT ) catalyzes the methylation of2-Hydroxyestradiol and 4-Hydroxyestradiol to 2-Methoxyestradiol and4-Metoxyestradiol, respectively [4].

Cytochrome 450 isoforms CYP1A2 and CYP3A4 catalyzes the16alpha-hydroxylation of Estradiol forming Estriol [2].Estriol is glucuronidated to Estriol 16-D-glucuronoside by UDPglucuronosyltransferase 2 family, polypeptide B11 ( UGT2B11 ) [5].

Other pathways of Estradiol metabolism include formation of glucuronideconjugates and sulfation. UDP glucuronosyltransferase 1 family, polypeptides A1 (UGT1A1 ) [6] and A10 ( UGT1A10 ) [6], and UDPglucuronosyltransferase 2 family, polypeptide B28 ( UGT2B28 ) [7]convert Estradiol to Estradiol 3-glucuronide.

Several sulfotransferases including Sulfotransferase family, cytosolic, 1A,phenol-preferring, members 1 ( SULT1A1 ) [8] and 3 ( SULT1A3 )[9], Sulfotransferase family 1E, estrogen-preferring, member 1 (SULT1E1 ) [10] and Sulfotransferase family, cytosolic, 2A,dehydroepiandrosterone (DHEA)-preferring, member 1 ( SULT2A1 ) [11]catalyze sulfation of Estradiol to 17beta-Estra-1,3,5-trien-3,17-diol3-sulfate.