2-Hydroxyestrone

2-Hydroxyestrone.svg skin-invert-image 200px 2,3-Dihydroxyestra-1,3,5(10)-trien-17-one (3aS,3bR,9bS,11aS)-7,8-Dihydroxy-11a-methyl-2,3,3a,3b,4,5,9b,10,11,11a-decahydro-1H-cyclopenta[a]phenanthren-1-one 2-OHE1; Estra-1,3,5(10)-trien-2,3-diol-17-one 362-06-1 1156 1627343 C05298 440623 389514 Oc1c(O)cc2[C@H]3CC[C@]4(C)C(CC[C@H]4[C@@H]3CCc2c1)=O 1S/C18H22O3/c1-18-7-6-11-12(14(18)4-5-17(18)21)3-2-10-8-15(19)16(20)9-13(10)11/h8-9,11-12,14,19-20H,2-7H2,1H3/t11-,12+,14-,18-/m0/s1 SWINWPBPEKHUOD-JPVZDGGYSA-N UQS3A06ILY 18 22 3 286.371 g/mol 2-Hydroxyestrone (2-OHE1), also known as estra-1,3,5(10)-trien-2,3-diol-17-one, is an endogenous, naturally occurring catechol estrogen and a major metabolite of estrone and estradiol. Michael Oettel Ekkehard Schillinger vanc Estrogens and Antiestrogens I: Physiology and Mechanisms of Action of Estrogens and Antiestrogens https://books.google.com/books?id=0BfrCAAAQBAJ&pg=PA235 6 December 2012 Springer Science & Business Media 978-3-642-58616-3 227 David Rakel vanc Integrative Medicine https://books.google.com/books?id=jlVtJzBwAcEC&pg=PA338 2012 Elsevier Health Sciences 978-1-4377-1793-8 338– Buchsbaum HJ The Menopause https://books.google.com/books?id=z0LuBwAAQBAJ&pg=PA65 6 December 2012 Springer Science & Business Media 978-1-4612-5525-3 64–65 It is formed irreversibly from estrone in the liver and to a lesser extent in other tissues via 2-hydroxylation mediated by cytochrome P450 enzymes, mainly the CYP3A and CYP1A subfamilies. 2-OHE1 is the most abundant catechol estrogen in the body. 2-Hydroxyestrone is not significantly uterotrophic in bioassays, whereas other hydroxylated estrogen metabolites including 2-hydroxyestradiol, 16α-hydroxyestrone, estriol (16α-hydroxyestradiol), 4-hydroxyestradiol, and 4-hydroxyestrone all are. Bhavnani BR, Nisker JA, Martin J, Aletebi F, Watson L, Milne JK Comparison of pharmacokinetics of a conjugated equine estrogen preparation (premarin) and a synthetic mixture of estrogens (C.E.S.) in postmenopausal women Journal of the Society for Gynecologic Investigation 7 3 175–83 2000 10865186 10.1016/s1071-5576(00)00049-6 In addition, although not antiestrogenic in the uterus, Martucci C, Fishman J Direction of estradiol metabolism as a control of its hormonal action--uterotrophic activity of estradiol metabolites Endocrinology 101 6 1709–15 December 1977 590186 10.1210/endo-101-6-1709 free Kono S, Brandon DD, Merriam GR, Loriaux DL, Lipsett MB Metabolic clearance rate and uterotropic activity of 2-hydroxyestrone in rats Endocrinology 108 1 40–3 January 1981 7460827 10.1210/endo-108-1-40 2-hydroxyestrone shows antiestrogenic effects on luteinizing hormone and prolactin levels. Martucci CP, Fishman J Impact of continuously administered catechol estrogens on uterine growth and luteinizing hormone secretion Endocrinology 105 6 1288–92 December 1979 499073 10.1210/endo-105-6-1288 Katayama S, Fishman J 2-Hydroxyestrone suppresses and 2-methoxyestrone augments the preovulatory prolactin surge in the cycling rat Endocrinology 110 4 1448–50 April 1982 7199421 10.1210/endo-110-4-1448 free Okatani Y, Fishman J Suppression of the preovulatory luteinizing hormone surge in the rat by 2-hydroxyestrone: relationship to endogenous estradiol levels Endocrinology 115 3 1082–9 September 1984 6378602 10.1210/endo-115-3-1082 Okatani Y, Fishman J Inhibition of the preovulatory prolactin surge in the rat by catechol estrogens: functional and temporal specificity Endocrinology 119 1 261–7 July 1986 3013588 10.1210/endo-119-1-261 The lack of estrogenic or antiestrogenic activity of 2-hydroxyestrone in the uterus may be attributable to an extremely high metabolic clearance rate. MacLusky NJ, Naftolin F, Krey LC, Franks S The catechol estrogens J. Steroid Biochem. 15 111–24 December 1981 6279963 10.1016/0022-4731(81)90265-x When incubated at very high concentrations or in combination with a catechol O-methyltransferase (COMT) inhibitor to prevent its metabolism, 2-hydroxyestrone shows antiestrogenic effects in estrogen receptor-positive human breast cancer cells.Gupta Mona McDougal Andrew Safe Stephen Estrogenic and antiestrogenic activities of 16α- and 2-hydroxy metabolites of 17β-estradiol in MCF-7 and T47D human breast cancer cells The Journal of Steroid Biochemistry and Molecular Biology 67 5–6 1998 413–419 0960-0760 10.1016/S0960-0760(98)00135-6 10030690 54268416 Schneider J, Huh MM, Bradlow HL, Fishman J Antiestrogen action of 2-hydroxyestrone on MCF-7 human breast cancer cells J. Biol. Chem. 259 8 4840–5 April 1984 10.1016/S0021-9258(17)42922-X 6325410 free 2-Hydroxyestrone dissociates from the estrogen receptors much more rapidly than does estradiol. Barnea ER, MacLusky NJ, Naftolin F Kinetics of catechol estrogen-estrogen receptor dissociation: a possible factor underlying differences in catechol estrogen biological activity Steroids 41 5 643–56 May 1983 6658896 10.1016/0039-128x(83)90030-2 27048999 See also 2-Methoxyestradiol Estrogen conjugate Lipoidal estrogen References External links Metabocard for 2-Hydroxyestrone (HMDB12623) - Human Metabolome Database Category:Catechol-O-methyltransferase inhibitors Category:Estranes Category:Human metabolites Category:Selective estrogen receptor modulators Category:Tyrosine hydroxylase inhibitors Category:Hydroxyarenes