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Estrone metabolism
Estrone metabolism

Object List (links open in MetaCore):

estriol, SULT2B1, 2.1.1.6, 3.1.6.2, 5.1.99.2, Estrone-3 sulfate, HSD17B8, HSD17B7, 1.1.1.62, Estrone, 2.8.2.4, 1.14.14.1, 1.14.14.1, 16beta-3,16- Dihydroxy-estra- 1,3,5-trien-17-one, 2.8.2.15, COMT, 16alpha-3,16- Dihydroxy-estra-1,3,5-trien-17-one, CYP2C19, 4-Hydroxyestrone, HSD17B2, 2.1.1.6, 3,4-dihydroxy-Estra-1,3,5-trien-17-one 4-methyl ether, CYP1A2, STS, HSD17B3, 2,3-dihydroxy-Estra-1,3,5-trien-17-one 2-methyl ether sulfate, 5.1.99.2, 2-Hydroxyestrone, 2,3-dihydroxy-Estra-1,3,5-trien-17-one 2-methyl ether, HSD17B1, CYP2C9, CYP3A5, 1.14.14.1, SULT1E1, CYP3A4

Description

Estrone metabolism.

Endogenous and exogenous estrogens undergo oxidative metabolism by hepatic microsomal cytochrome P-450. Aromatic hydroxylation at either the C2 or C4 position is a major route of Estrone metabolism in humans and other mammals, although there are less 4-hydroxylation than 2-hydroxylation events.

Several cytochrome P450 isoforms including Cytochrome P450, family 2, subfamily C, polypeptide 9 ( CYP2C9 ), Cytochrome P450, family 3, subfamily A, polypeptides 4 ( CYP3A4 ) and 5 ( CYP3A5 ), Cytochrome P450, family 1, subfamily A, polypeptide 2 ( CYP1A2 ), and Cytochrome P450, family 2, subfamily C, polypeptide 19 ( CYP2C19 ) [1] catalyze the hydroxylation of Estrone to 2-Hydroxyestrone or/and 4-Hydroxyestrone. Further, Catechol-O-methyltransferase ( COMT ) catalyzes the methylation of 2-Hydroxyestrone and 4-Hydroxyestrone to corresponding 2-Methoxyestrone and 4-Metoxyestrone [2].

CYP3A4 [3], [4], CYP3A5 [3], [4], and CYP2C19 [5] also catalyze 16alpha-hydroxylation of Estrone forming 16alpha-Hydroxyestrone. 16-Hydroxysteroid epimerase converts 16alpha-Hydroxyestrone to 16beta-Hydroxyestrone [6].

16alpha-Hydroxyestrone is also formed via Estriol oxidation by Hydroxysteroid (17-beta) dehydrogenases 1, 2, 3, 7 and 8 ( HSD17B1, HSD17B2, HSD17B3, HSD17B7 and HSD17B8).

Sulfotransferase family 1E, estrogen-preferring, member 1 ( SULT1E1 ) [7] catalyzes sulfation of Estrone to Estrone 3-sulfate. Reverse reaction, the hydrolysis of Estrone 3-sulfate, is catalyzed by Steroid sulfatase (microsomal), isozyme S ( STS ) [8].

References:

  1. Lee AJ, Cai MX, Thomas PE, Conney AH, Zhu BT
    Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology 2003 Aug;144(8):3382-98
  2. Dawling S, Roodi N, Mernaugh RL, Wang X, Parl FF
    Catechol-O-methyltransferase (COMT)-mediated metabolism of catechol estrogens: comparison of wild-type and variant COMT isoforms. Cancer research 2001 Sep 15;61(18):6716-22
  3. Huang Z, Guengerich FP, Kaminsky LS
    16Alpha-hydroxylation of estrone by human cytochrome P4503A4/5. Carcinogenesis 1998 May;19(5):867-72
  4. Lee AJ, Mills LH, Kosh JW, Conney AH, Zhu BT
    NADPH-dependent metabolism of estrone by human liver microsomes. The Journal of pharmacology and experimental therapeutics 2002 Mar;300(3):838-49
  5. Cribb AE, Knight MJ, Dryer D, Guernsey J, Hender K, Tesch M, Saleh TM
    Role of polymorphic human cytochrome P450 enzymes in estrone oxidation. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2006 Mar;15(3):551-8
  6. Dahm K, Lindlau M, Breuer H
    [Steroid epimerase--a new enzyme of estrogen metabolism] Biochimica et biophysica acta 1968 Jun 4;159(2):377-89
  7. Tseng L, Lee LY, Mazella J
    Estrogen sulfotransferase in human placenta. Journal of steroid biochemistry 1985 May;22(5):611-5
  8. Dibbelt L, Kuss E
    Human placental steroid-sulfatase solubilized with a cholic-acid derivative: molecular mass, kinetic properties and susceptibility to glycosidases. Hoppe-Seyler's Zeitschrift fur physiologische Chemie 1984 Sep;365(9):1145-53