16α-Hydroxyestrone

16α-Hydroxyestrone
Names
Preferred 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
CAS Number
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.164.941
Edit this at Wikidata
PubChem CID
UNII
InChI
  • 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
SMILES
  • C[C@]12CC[C@H]3[C@H]([C@@H]1C[C@H](C2=O)O)CCC4=C3C=CC(=C4)O
Properties
Chemical formula
 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
EstrogenER RBA (%)Uterine weight (%)UterotrophyLH levels (%)SHBG RBA (%)
Control–100–100–
Estradiol100506 ± 20+++12–19100
Estrone11 ± 8490 ± 22+++ ?20
Estriol10 ± 4468 ± 30+++8–183
Estetrol0.5 ± 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: See template.

See also

  • 2-Hydroxyestrone
  • 2-Hydroxyestradiol
  • 16β-Hydroxyestrone
  • 16-Ketoestrone
  • 16α-Hydroxydehydroepiandrosterone
  • 16α-Hydroxyandrostenedione
  • 15α-Hydroxydehydroepiandrosterone

References

  1. 1 2 3 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. 1 2 3 4 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. 1 2 Velardo, Joseph Thomas (1964). "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.



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