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:
- 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
- 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
- Huang Z, Guengerich FP, Kaminsky LS
16Alpha-hydroxylation of estrone by human cytochrome P4503A4/5.
Carcinogenesis 1998 May;19(5):867-72
- 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
- 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
- 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
- Tseng L, Lee LY, Mazella J
Estrogen sulfotransferase in human placenta.
Journal of steroid biochemistry 1985 May;22(5):611-5
- 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
