Edge Rewrite
restyle Source code View original
// HTMLRewriter · presentation

This page was redesigned at the edge.

Cloudflare fetched the original article and streamed it through HTMLRewriter to apply an entirely new visual system without rebuilding the source page.

Jump to content

2-Hydroxyestrone

From Wikipedia, the free encyclopedia
(Redirected from 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
  • Oc1c(O)cc2[C@H]3CC[C@]4(C)C(CC[C@H]4[C@@H]3CCc2c1)=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
EstrogenERTooltip Estrogen receptor RBATooltip relative binding affinity (%)Uterine weight (%)UterotrophyLHTooltip Luteinizing hormone levels (%)SHBGTooltip Sex hormone-binding globulin RBATooltip relative binding affinity (%)
Control–100–100–
Estradiol (E2)100506 ± 20+++12–19100
Estrone (E1)11 ± 8490 ± 22+++?20
Estriol (E3)10 ± 4468 ± 30+++8–183
Estetrol (E4)0.5 ± 0.2?Inactive?1
17α-Estradiol4.2 ± 0.8????
2-Hydroxyestradiol24 ± 7285 ± 8+b31–6128
2-Methoxyestradiol0.05 ± 0.04101Inactive?130
4-Hydroxyestradiol45 ± 12????
4-Methoxyestradiol1.3 ± 0.2260++?9
4-Fluoroestradiola180 ± 43?+++??
2-Hydroxyestrone1.9 ± 0.8130 ± 9Inactive110–1428
2-Methoxyestrone0.01 ± 0.00103 ± 7Inactive95–100120
4-Hydroxyestrone11 ± 4351++21–5035
4-Methoxyestrone0.13 ± 0.04338++65–9212
16α-Hydroxyestrone2.8 ± 1.0552 ± 42+++7–24<0.5
2-Hydroxyestriol0.9 ± 0.3302+b??
2-Methoxyestriol0.01 ± 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

[edit]

References

[edit]
  1. 1 2 3 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. 1 2 3 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. 1 2 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.
[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=2-Hydroxyestrone&oldid=1342306991"