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2-Hydroxyestrone

2-Hydroxyestrone
Names
IUPAC name
2,3-Dihydroxyestra-1,3,5(10)-trien-17-one
Systematic IUPAC name
(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
Other names
2-OHE1; Estra-1,3,5(10)-trien-2,3-diol-17-one
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.164.607 Edit this at Wikidata
KEGG
UNII
  • InChI=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
    Key: SWINWPBPEKHUOD-JPVZDGGYSA-N
  • C[C@]12CC[C@H]3[C@H]([C@@H]1CCC2=O)CCC4=CC(=C(C=C34)O)O
Properties
C18H22O3
Molar mass 286.371 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

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.[1][2][3] 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.[1][3] 2-OHE1 is the most abundant catechol estrogen in the body.[3]

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.[1][4] In addition, although not antiestrogenic in the uterus,[5][6] 2-hydroxyestrone shows antiestrogenic effects on luteinizing hormone and prolactin levels.[7][8][9][10] The lack of estrogenic or antiestrogenic activity of 2-hydroxyestrone in the uterus may be attributable to an extremely high metabolic clearance rate.[6][11] 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.[12][13]

2-Hydroxyestrone dissociates from the estrogen receptors much more rapidly than does estradiol.[14]

Selected biological properties of endogenous estrogens in rats
Estrogen ERTooltip Estrogen receptor RBATooltip relative binding affinity (%) Uterine weight (%) Uterotrophy LHTooltip Luteinizing hormone levels (%) SHBGTooltip Sex hormone-binding globulin RBATooltip relative binding affinity (%)
Control – 100 – 100 –
Estradiol (E2) 100 506 ± 20 +++ 12–19 100
Estrone (E1) 11 ± 8 490 ± 22 +++ ? 20
Estriol (E3) 10 ± 4 468 ± 30 +++ 8–18 3
Estetrol (E4) 0.5 ± 0.2 ? Inactive ? 1
17α-Estradiol 4.2 ± 0.8 ? ? ? ?
2-Hydroxyestradiol 24 ± 7 285 ± 8 +b 31–61 28
2-Methoxyestradiol 0.05 ± 0.04 101 Inactive ? 130
4-Hydroxyestradiol 45 ± 12 ? ? ? ?
4-Methoxyestradiol 1.3 ± 0.2 260 ++ ? 9
4-Fluoroestradiola 180 ± 43 ? +++ ? ?
2-Hydroxyestrone 1.9 ± 0.8 130 ± 9 Inactive 110–142 8
2-Methoxyestrone 0.01 ± 0.00 103 ± 7 Inactive 95–100 120
4-Hydroxyestrone 11 ± 4 351 ++ 21–50 35
4-Methoxyestrone 0.13 ± 0.04 338 ++ 65–92 12
16α-Hydroxyestrone 2.8 ± 1.0 552 ± 42 +++ 7–24 <0.5
2-Hydroxyestriol 0.9 ± 0.3 302 +b ? ?
2-Methoxyestriol 0.01 ± 0.00 ? Inactive ? 4
Notes: Values are mean ± SD or range. ER RBA = Relative binding affinity to estrogen receptors of rat uterine cytosol. Uterine weight = Percentage change in uterine wet weight of ovariectomized rats after 72 hours with continuous administration of 1 μg/hour via subcutaneously implanted osmotic pumps. LH levels = Luteinizing hormone levels relative to baseline of ovariectomized rats after 24 to 72 hours of continuous administration via subcutaneous implant. Footnotes: a = Synthetic (i.e., not endogenous). b = Atypical uterotrophic effect which plateaus within 48 hours (estradiol's uterotrophy continues linearly up to 72 hours). Sources: [15][16][17][18][19][20][21][22][23]

See also

References

  1. ^ a b c Oettel M, Schillinger E (6 December 2012). Estrogens and Antiestrogens I: Physiology and Mechanisms of Action of Estrogens and Antiestrogens. Springer Science & Business Media. p. 227. ISBN 978-3-642-58616-3.
  2. ^ Rakel D (2012). Integrative Medicine. Elsevier Health Sciences. pp. 338–. ISBN 978-1-4377-1793-8.
  3. ^ a b c Buchsbaum HJ (6 December 2012). The Menopause. Springer Science & Business Media. pp. 64–65. ISBN 978-1-4612-5525-3.
  4. ^ Bhavnani BR, Nisker JA, Martin J, Aletebi F, Watson L, Milne JK (2000). "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. doi:10.1016/s1071-5576(00)00049-6. PMID 10865186.
  5. ^ Martucci C, Fishman J (December 1977). "Direction of estradiol metabolism as a control of its hormonal action--uterotrophic activity of estradiol metabolites". Endocrinology. 101 (6): 1709–15. doi:10.1210/endo-101-6-1709. PMID 590186.
  6. ^ a b Kono S, Brandon DD, Merriam GR, Loriaux DL, Lipsett MB (January 1981). "Metabolic clearance rate and uterotropic activity of 2-hydroxyestrone in rats". Endocrinology. 108 (1): 40–3. doi:10.1210/endo-108-1-40. PMID 7460827.
  7. ^ Martucci CP, Fishman J (December 1979). "Impact of continuously administered catechol estrogens on uterine growth and luteinizing hormone secretion". Endocrinology. 105 (6): 1288–92. doi:10.1210/endo-105-6-1288. PMID 499073.
  8. ^ Katayama S, Fishman J (April 1982). "2-Hydroxyestrone suppresses and 2-methoxyestrone augments the preovulatory prolactin surge in the cycling rat". Endocrinology. 110 (4): 1448–50. doi:10.1210/endo-110-4-1448. PMID 7199421.
  9. ^ Okatani Y, Fishman J (September 1984). "Suppression of the preovulatory luteinizing hormone surge in the rat by 2-hydroxyestrone: relationship to endogenous estradiol levels". Endocrinology. 115 (3): 1082–9. doi:10.1210/endo-115-3-1082. PMID 6378602.
  10. ^ Okatani Y, Fishman J (July 1986). "Inhibition of the preovulatory prolactin surge in the rat by catechol estrogens: functional and temporal specificity". Endocrinology. 119 (1): 261–7. doi:10.1210/endo-119-1-261. PMID 3013588.
  11. ^ MacLusky NJ, Naftolin F, Krey LC, Franks S (December 1981). "The catechol estrogens". J. Steroid Biochem. 15: 111–24. doi:10.1016/0022-4731(81)90265-x. PMID 6279963.
  12. ^ Gupta, Mona; McDougal, Andrew; Safe, Stephen (1998). "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): 413–419. doi:10.1016/S0960-0760(98)00135-6. ISSN 0960-0760. PMID 10030690. S2CID 54268416.
  13. ^ Schneider J, Huh MM, Bradlow HL, Fishman J (April 1984). "Antiestrogen action of 2-hydroxyestrone on MCF-7 human breast cancer cells". J. Biol. Chem. 259 (8): 4840–5. doi:10.1016/S0021-9258(17)42922-X. PMID 6325410.
  14. ^ Barnea ER, MacLusky NJ, Naftolin F (May 1983). "Kinetics of catechol estrogen-estrogen receptor dissociation: a possible factor underlying differences in catechol estrogen biological activity". Steroids. 41 (5): 643–56. doi:10.1016/0039-128x(83)90030-2. PMID 6658896. S2CID 27048999.
  15. ^ Martucci C, Fishman J (March 1976). "Uterine estrogen receptor binding of catecholestrogens and of estetrol (1,3,5(10)-estratriene-3,15alpha,16alpha,17beta-tetrol)". Steroids. 27 (3): 325–333. doi:10.1016/0039-128x(76)90054-4. PMID 178074. S2CID 54412821.
  16. ^ Martucci C, Fishman J (December 1977). "Direction of estradiol metabolism as a control of its hormonal action--uterotrophic activity of estradiol metabolites". Endocrinology. 101 (6): 1709–1715. doi:10.1210/endo-101-6-1709. PMID 590186.
  17. ^ Fishman J, Martucci C (December 1978). "Differential biological activity of estradiol metabolites". Pediatrics. 62 (6 Pt 2): 1128–1133. doi:10.1542/peds.62.6.1128. PMID 724350. S2CID 29609115.
  18. ^ Martucci CP, Fishman J (December 1979). "Impact of continuously administered catechol estrogens on uterine growth and luteinizing hormone secretion". Endocrinology. 105 (6): 1288–1292. doi:10.1210/endo-105-6-1288. PMID 499073.
  19. ^ Fishman J, Martucci CP (1980). "New Concepts of Estrogenic Activity: the Role of Metabolites in the Expression of Hormone Action". In Pasetto N, Paoletti R, Ambrus JL (eds.). The Menopause and Postmenopause. pp. 43–52. doi:10.1007/978-94-011-7230-1_5. ISBN 978-94-011-7232-5.
  20. ^ Fishman J, Martucci C (September 1980). "Biological properties of 16 alpha-hydroxyestrone: implications in estrogen physiology and pathophysiology". The Journal of Clinical Endocrinology and Metabolism. 51 (3): 611–615. doi:10.1210/jcem-51-3-611. PMID 7190977.
  21. ^ Martucci CP (July 1983). "The role of 2-methoxyestrone in estrogen action". Journal of Steroid Biochemistry. 19 (1B): 635–638. doi:10.1016/0022-4731(83)90229-7. PMID 6310247.
  22. ^ Fishman J, Martucci C (1980). "Dissociation of biological activities in metabolites of estradiol". In McLachlan JA (ed.). Estrogens in the Environment: Proceedings of the Symposium on Estrogens in the Environment, Raleigh, North Carolina, U.S.A., September 10-12, 1979. Elsevier. pp. 131–145. ISBN 9780444003720.
  23. ^ Kuhl H (August 2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric. 8 Suppl 1: 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324.
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