Chemistry:2-Hydroxyestrone

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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]

v · d · e Selected biological properties of endogenous estrogens in rats
Estrogen ER RBA (%) Uterine weight (%) Uterotrophy LH levels (%) SHBG RBA (%)
Control – 100 – 100 –
Estradiol 100 506 ± 20 +++ 12–19 100
Estrone 11 ± 8 490 ± 22 +++ ? 20
Estriol 10 ± 4 468 ± 30 +++ 8–18 3
Estetrol 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: See template.

See also

References

  1. ↑ 1.0 1.1 1.2 Oettel, Michael; Schillinger, Ekkehard (6 December 2012). Estrogens and Antiestrogens I: Physiology and Mechanisms of Action of Estrogens and Antiestrogens. Springer Science & Business Media. pp. 227. ISBN 978-3-642-58616-3. https://books.google.com/books?id=0BfrCAAAQBAJ&pg=PA235. 
  2. ↑ Rakel, David (2012). Integrative Medicine. Elsevier Health Sciences. pp. 338–. ISBN 978-1-4377-1793-8. https://books.google.com/books?id=jlVtJzBwAcEC&pg=PA338. 
  3. ↑ 3.0 3.1 3.2 The Menopause. Springer Science & Business Media. 6 December 2012. pp. 64–65. ISBN 978-1-4612-5525-3. https://books.google.com/books?id=z0LuBwAAQBAJ&pg=PA65. 
  4. ↑ "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. doi:10.1016/s1071-5576(00)00049-6. PMID 10865186. 
  5. ↑ "Direction of estradiol metabolism as a control of its hormonal action--uterotrophic activity of estradiol metabolites". Endocrinology 101 (6): 1709–15. December 1977. doi:10.1210/endo-101-6-1709. PMID 590186. 
  6. ↑ 6.0 6.1 "Metabolic clearance rate and uterotropic activity of 2-hydroxyestrone in rats". Endocrinology 108 (1): 40–3. January 1981. doi:10.1210/endo-108-1-40. PMID 7460827. 
  7. ↑ "Impact of continuously administered catechol estrogens on uterine growth and luteinizing hormone secretion". Endocrinology 105 (6): 1288–92. December 1979. doi:10.1210/endo-105-6-1288. PMID 499073. 
  8. ↑ "2-Hydroxyestrone suppresses and 2-methoxyestrone augments the preovulatory prolactin surge in the cycling rat". Endocrinology 110 (4): 1448–50. April 1982. doi:10.1210/endo-110-4-1448. PMID 7199421. 
  9. ↑ "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. doi:10.1210/endo-115-3-1082. PMID 6378602. 
  10. ↑ "Inhibition of the preovulatory prolactin surge in the rat by catechol estrogens: functional and temporal specificity". Endocrinology 119 (1): 261–7. July 1986. doi:10.1210/endo-119-1-261. PMID 3013588. 
  11. ↑ "The catechol estrogens". J. Steroid Biochem. 15: 111–24. December 1981. 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. 
  13. ↑ "Antiestrogen action of 2-hydroxyestrone on MCF-7 human breast cancer cells". J. Biol. Chem. 259 (8): 4840–5. April 1984. doi:10.1016/S0021-9258(17)42922-X. PMID 6325410. 
  14. ↑ "Kinetics of catechol estrogen-estrogen receptor dissociation: a possible factor underlying differences in catechol estrogen biological activity". Steroids 41 (5): 643–56. May 1983. doi:10.1016/0039-128x(83)90030-2. PMID 6658896. 



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