16α-Hydroxyestrone

16α-Hydroxyestrone
Names
IUPAC name
3,16α-Dihydroxyestra-1,3,5(10)-trien-17-one
Systematic IUPAC name
(2R,3aS,3bR,9bS,11aS)-2,7-Dihydroxy-11a-methyl-2,3,3a,3b,4,5,9b,10,11,11a-decahydro-1H-cyclopenta[a]phenanthren-1-one
Other names
Hydroxyestrone; 16-Hydroxyestrone
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.164.941
UNII
  • InChI=1S/C18H22O3/c1-18-7-6-13-12-5-3-11(19)8-10(12)2-4-14(13)15(18)9-16(20)17(18)21/h3,5,8,13-16,19-20H,2,4,6-7,9H2,1H3/t13-,14-,15+,16-,18+/m1/s1
  • C[C@]12CC[C@H]3[C@H]([C@@H]1C[C@H](C2=O)O)CCC4=C3C=CC(=C4)O
Properties
C18H22O3
Molar mass 286.371 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

16α-Hydroxyestrone (16α-OH-E1), or hydroxyestrone, also known as estra-1,3,5(10)-triene-3,16α-diol-17-one, is an endogenous steroidal estrogen and a major metabolite of estrone, as well as an intermediate in the biosynthesis of estriol.[1][2] It is a potent estrogen similarly to estrone, and it has been suggested that the ratio of 16α-hydroxyestrone to 2-hydroxyestrone, the latter being much less estrogenic in comparison and even antiestrogenic in the presence of more potent estrogens like estradiol, may be involved in the pathophysiology of breast cancer.[1] Conversely, 16α-hydroxyestrone may help to protect against osteoporosis.[1]

In terms of relative binding affinity (RBA) for the rat uterine estrogen receptor, 16α-hydroxyestrone showed 2.8% of the affinity of estradiol.[3] For comparison, estrone had 11% of the affinity and estriol had 10% of the affinity of estradiol.[3] In contrast to other estrogens, the binding of 16α-hydroxyestrone to the estrogen receptor is reported to be covalent and irreversible.[4][5][6][7] 16α-Hydroxyestrone has been reported to have 25% of the vaginal estrogenic potency of estradiol.[3] The maximal uterotrophic and antigonadotropic effect of 16α-hydroxyestrone was equivalent to those of estradiol and estriol, indicating that 16α-hydroxyestrone is a fully effective estrogen.[3][8] However, 16α-hydroxyestrone was much less potent than estradiol or estrone.[8]

The C3 and C16α diacetate ester of 16α-hydroxyestrone, hydroxyestrone diacetate (brand names Colpoginon, Colpormon, Hormobion, and Hormocervix), has been marketed and used medically as an estrogen in Europe.[9][10]

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: [11][12][13][14][15][16][17][18][19]

See also

References

  1. ^ a b c Rakel D (2012). Integrative Medicine. Elsevier Health Sciences. pp. 338–339. ISBN 978-1-4377-1793-8.
  2. ^ Vitamins and Hormones. Academic Press. 7 September 2005. pp. 282–. ISBN 978-0-08-045978-3.
  3. ^ a b c d Fishman J, Martucci C (September 1980). "Biological properties of 16 alpha-hydroxyestrone: implications in estrogen physiology and pathophysiology". J. Clin. Endocrinol. Metab. 51 (3): 611–5. doi:10.1210/jcem-51-3-611. PMID 7190977.
  4. ^ Oettel M, Schillinger E (6 December 2012). Estrogens and Antiestrogens I: Physiology and Mechanisms of Action of Estrogens and Antiestrogens. Springer Science & Business Media. pp. 252–. ISBN 978-3-642-58616-3.
  5. ^ Swaneck GE, Fishman J (November 1988). "Covalent binding of the endogenous estrogen 16 alpha-hydroxyestrone to estradiol receptor in human breast cancer cells: characterization and intranuclear localization". Proc. Natl. Acad. Sci. U.S.A. 85 (21): 7831–5. Bibcode:1988PNAS...85.7831S. doi:10.1073/pnas.85.21.7831. PMC 282290. PMID 3186693.
  6. ^ Zhu BT, Conney AH (January 1998). "Functional role of estrogen metabolism in target cells: review and perspectives". Carcinogenesis. 19 (1): 1–27. doi:10.1093/carcin/19.1.1. PMID 9472688.
  7. ^ Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324.
  8. ^ a b Velardo, Joseph Thomas. "The Actions of Steroid Hormones on Estradiol-17β in Uterine Growth and Enzymorphology". Hormonal Steroids Biochemistry, Pharmacology, and Therapeutics. pp. 463–490. doi:10.1016/B978-0-12-395506-7.50065-0. ISBN 9780123955067.
  9. ^ Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 1250–. ISBN 978-3-88763-075-1.
  10. ^ Muller NF, Dessing RP, European Society of Clinical Pharmacy (19 June 1998). European Drug Index: European Drug Registrations (Fourth ed.). CRC Press. pp. 289–. ISBN 978-3-7692-2114-5.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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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