Estradiol sulfate
Iupacname17β-Hydroxyestra-1,3,5(10)-trien-3-yl hydrogen sulfate
Systematicname(1S,3aS,3bR,9bS,11aS)-1-Hydroxy-11a-methyl-2,3,3a,3b,4,5,9b,10,11,11a-decahydro-1H-cyclopenta[a]phenanthren-7-yl hydrogen sulfate
OthernamesEstra-1,3,5(10)-triene-3,17β-diol 3-sulfate

Estradiol sulfate (E2S), or 17β-estradiol 3-sulfate,[1] is a natural, endogenous steroid and an estrogen ester.[2] E2S itself is biologically inactive,[3] but it can be converted by steroid sulfatase (also called estrogen sulfatase) into estradiol, which is a potent estrogen.[2][4][5] Simultaneously, estrogen sulfotransferases convert estradiol to E2S, resulting in an equilibrium between the two steroids in various tissues.[2][5] Estrone and E2S are the two immediate metabolic sources of estradiol.[6] E2S can also be metabolized into estrone sulfate (E1S), which in turn can be converted into estrone and estradiol.[7] Circulating concentrations of E2S are much lower than those of E1S.[1] High concentrations of E2S are present in breast tissue, and E2S has been implicated in the biology of breast cancer via serving as an active reservoir of estradiol.[2][4]

As the sodium salt sodium estradiol sulfate, E2S is present as a minor constituent (0.9%) of conjugated equine estrogens (CEEs), or Premarin.[8] It effectively functions as a prodrug to estradiol in this preparation, similarly to E1S. E2S is also formed as a metabolite of estradiol, as well as of estrone and E1S.[9][10] Aside from its presence in CEEs, E2S is not available as a commercial pharmaceutical drug.[11]

E2S shows about 10,000-fold lower potency in activating the estrogen receptors relative to estradiol in vitro.[12] It is 10-fold less potent than estrone sulfate orally in terms of in vivo uterotrophic effect in rats.[13] Estrogen sulfates like estradiol sulfate or estrone sulfate are about twice as potent as the corresponding free estrogens in terms of estrogenic effect when given orally to rodents.[14] This in part led to the introduction of conjugated estrogens (Premarin), which are primarily estrone sulfate, in 1941.[14]

Although inactive at steroid hormone receptors, E2S has been found to act as a potent inhibitor of glutathione S-transferase,[15] an enzyme that contributes to the inactivation of estradiol via conversion of it into an estradiol-glutathione conjugate.[16] As such, E2S can indirectly serve as a positive effector of estrogen signaling.[15]

Estradiol levels are about 1.5- to 4-fold higher than E2S levels in women. This is in contrast to E1S, the levels of which are about 10 to 15 times higher than those of estrone.[17]

E2S at an oral dosage of 5 mg/day in women resulted in inhibition of ovulation in 89% of cycles (47 of 53).[18]

See also

References

  1. ^ F. A. Kincl & J. R. Pasqualini (22 October 2013). Hormones and the Fetus: Volume 1: Production, Concentration and Metabolism During Pregnancy. Elsevier Science. pp. 39–. ISBN 978-1-4832-8538-2.
  2. ^ Peter J. O'Brien & William Robert Bruce (2 December 2009). Endogenous Toxins: Targets for Disease Treatment and Prevention, 2 Volume Set. John Wiley & Sons. pp. 869–. ISBN 978-3-527-32363-0.
  3. ^ Wang, Li-Quan & James, Margaret O. (2005). "Sulfotransferase 2A1 forms estradiol-17-sulfate and celecoxib switches the dominant product from estradiol-3-sulfate to estradiol-17-sulfate". The Journal of Steroid Biochemistry and Molecular Biology. 96 (5): 367–374. doi:10.1016/j.jsbmb.2005.05.002. ISSN 0960-0760. PMID 16011896. S2CID 24671971
  4. ^ Jorge R. Pasqualini (17 July 2002). Breast Cancer: Prognosis, Treatment, and Prevention. CRC Press. pp. 195–. ISBN 978-0-203-90924-9.
  5. ^ IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; World Health Organization; International Agency for Research on Cancer (2007). Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy. World Health Organization. pp. 279–. ISBN 978-92-832-1291-1.
  6. ^ G. Leclercq; S. Toma; R. Paridaens; J. C. Heuson (6 December 2012). Clinical Interest of Steroid Hormone Receptors in Breast Cancer. Springer Science & Business Media. pp. 2105–. ISBN 978-3-642-82188-2.
  7. ^ A. T. Gregoire (13 March 2013). Contraceptive Steroids: Pharmacology and Safety. Springer Science & Business Media. pp. 109–. ISBN 978-1-4613-2241-2.
  8. ^ Marc A. Fritz & Leon Speroff (28 March 2012). Clinical Gynecologic Endocrinology and Infertility. Lippincott Williams & Wilkins. pp. 751–. ISBN 978-1-4511-4847-3.
  9. ^ Christian Lauritzen & John W. W. Studd (22 June 2005). Current Management of the Menopause. CRC Press. pp. 364–. ISBN 978-0-203-48612-2.
  10. ^ Ryan J. Huxtable (11 November 2013). Biochemistry of Sulfur. Springer Science & Business Media. pp. 312–. ISBN 978-1-4757-9438-0.
  11. ^ King, Roberta; Ghosh, Anasuya; Wu, Jinfang (2006). "Inhibition of human phenol and estrogen sulfotransferase by certain non-steroidal anti-inflammatory agents". Current Drug Metabolism. 7 (7): 745–753. doi:10.2174/138920006778520615. ISSN 1389-2002. PMC 2105742. PMID 17073578
  12. ^ Coldham NG, Dave M, Sivapathasundaram S, McDonnell DP, Connor C, Sauer MJ (July 1997). "Evaluation of a recombinant yeast cell estrogen screening assay". Environ. Health Perspect.. 105 (7): 734–42. doi:10.1289/ehp.97105734. PMC 1470103. PMID 9294720
  13. ^ Bhavnani BR (November 1988). "The saga of the ring B unsaturated equine estrogens". Endocr. Rev.. 9 (4): 396–416. doi:10.1210/edrv-9-4-396. PMID 3065072
  14. ^ Herr, F.; Revesz, C.; Manson, A. J.; Jewell, J. B. (1970). "Biological Properties of Estrogen Sulfates". Chemical and Biological Aspects of Steroid Conjugation. pp. 368–408. doi:10.1007/978-3-642-95177-0_8. ISBN 978-3-642-95179-4.
  15. ^ Runge-Morris MA (1997). "Regulation of expression of the rodent cytosolic sulfotransferases". FASEB J.. 11 (2): 109–17. doi:10.1096/fasebj.11.2.9039952. PMID 9039952. S2CID 22112485
  16. ^ Singh D, Pandey RS (1996). "Glutathione-S-transferase in rat ovary: its changes during estrous cycle and increase in its activity by estradiol-17 beta". Indian J. Exp. Biol.. 34 (11): 1158–60. PMID 9055636
  17. ^ Cowie, Alfred T.; Forsyth, Isabel A.; Hart, Ian C. (1980). "Growth and Development of the Mammary Gland". Hormonal Control of Lactation. Vol. 15. Monographs on Endocrinology. pp. 58–145. doi:10.1007/978-3-642-81389-4_3. ISBN 978-3-642-81391-7. ISSN 0077-1015. PMID 6250026
  18. ^ Gual C, Becerra C, Rice-Wray E, Goldzieher JW (February 1967). "Inhibition of ovulation by estrogens". Am J Obstet Gynecol. 97 (4): 443–7. doi:10.1016/0002-9378(67)90555-8. PMID 4163201