Estradiol sulfateのソースを表示

{{Chembox
<!-- Images -->
| ImageFile = Estradiol sulfate.svg
| ImageSize = 225px
| ImageAlt =
<!-- Names -->
| IUPACName = 17β-Hydroxyestra-1,3,5(10)-trien-3-yl hydrogen sulfate
| SystematicName = (1''S'',3a''S'',3b''R'',9b''S'',11a''S'')-1-Hydroxy-11a-methyl-2,3,3a,3b,4,5,9b,10,11,11a-decahydro-1''H''-cyclopenta[''a'']phenanthren-7-yl hydrogen sulfate
| OtherNames = Estra-1,3,5(10)-triene-3,17β-diol 3-sulfate
<!-- Sections -->
| Section1 = {{Chembox Identifiers
| CASNo = 481-96-9
| CASNoOther = 4999-79-5 ([[sodium]])
| ChemSpiderID = 59790
| InChI = 1S/C18H24O5S/c1-18-9-8-14-13-5-3-12(23-24(20,21)22)10-11(13)2-4-15(14)16(18)6-7-17(18)19/h3,5,10,14-17,19H,2,4,6-9H2,1H3,(H,20,21,22)/t14-,15-,16+,17+,18+/m1/s1
| InChIKey = QZIGLSSUDXBTLJ-ZBRFXRBCSA-N
| PubChem = 66416
| SMILES = CC12CCC3C(C1CCC2O)CCC4=C3C=CC(=C4)OS(=O)(=O)O
| UNII = 4NKQ3751P6
| ChEBI = 4866
| ChEMBL = 1628111
  }}
| Section2 = {{Chembox Properties
| C=18 | H=24 | O=5 | S=1
| MolarMass = 352.445 g/mol
| Appearance =
| Density =
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| Section3 = {{Chembox Hazards
| MainHazards =
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'''Estradiol sulfate''' ('''E2S'''), or '''17β-estradiol 3-sulfate''',<ref name="KinclPasqualini2013">{{cite book|author1=F. A. Kincl|author2=J. R. Pasqualini|title=Hormones and the Fetus: Volume 1: Production, Concentration and Metabolism During Pregnancy|url=https://books.google.com/books?id=0ly2AgAAQBAJ&pg=PA39|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4832-8538-2|pages=39–}}</ref> is a [[natural product|natural]], [[endogenous]] steroid and an [[estrogen ester]].<ref name="O'BrienBruce2009">{{cite book|author1=Peter J. O'Brien|author2=William Robert Bruce|title=Endogenous Toxins: Targets for Disease Treatment and Prevention, 2 Volume Set|url=https://books.google.com/books?id=UaLR0RSuXvsC&pg=PA869|date=2 December 2009|publisher=John Wiley & Sons|isbn=978-3-527-32363-0|pages=869–}}</ref> E2S itself is biologically inactive,<ref name="WangJames2005">{{cite journal | first1=Li-Quan | last1=Wang | title=Sulfotransferase 2A1 forms estradiol-17-sulfate and celecoxib switches the dominant product from estradiol-3-sulfate to estradiol-17-sulfate | last2=James | first2=Margaret O. | journal=The Journal of Steroid Biochemistry and Molecular Biology | year=2005 | volume=96 | issue=5 | pages=367–374 | issn=0960-0760 | doi=10.1016/j.jsbmb.2005.05.002 | pmid=16011896| s2cid=24671971 }}</ref> but it can be converted by [[steroid sulfatase]] (also called estrogen sulfatase) into [[estradiol]], which is a potent [[estrogen]].<ref name="O'BrienBruce2009" /><ref name="Pasqualini2002">{{cite book|author=Jorge R. Pasqualini|title=Breast Cancer: Prognosis, Treatment, and Prevention|url=https://books.google.com/books?id=l4XLBQAAQBAJ&pg=PA195|date=17 July 2002|publisher=CRC Press|isbn=978-0-203-90924-9|pages=195–}}</ref><ref name="HumansOrganization2007">{{cite book|author1=IARC Working Group on the Evaluation of Carcinogenic Risks to Humans|author2=World Health Organization|author3=International Agency for Research on Cancer|title=Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy|url=https://books.google.com/books?id=aGDU5xibtNgC&pg=PA279|year=2007|publisher=World Health Organization|isbn=978-92-832-1291-1|pages=279–}}</ref> Simultaneously, [[estrogen sulfotransferase]]s convert estradiol to E2S, resulting in an [[Chemical equilibrium|equilibrium]] between the two steroids in various tissues.<ref name="O'BrienBruce2009" /><ref name="HumansOrganization2007" /> [[Estrone]] and E2S are the two immediate [[precursor (biochemistry)|metabolic sources]] of estradiol.<ref name="LeclercqToma2012">{{cite book|author1=G. Leclercq|author2=S. Toma|author3=R. Paridaens|author4=J. C. Heuson|title=Clinical Interest of Steroid Hormone Receptors in Breast Cancer|url=https://books.google.com/books?id=31cyBwAAQBAJ&pg=PA2105|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-82188-2|pages=2105–}}</ref> E2S can also be metabolized into [[estrone sulfate]] (E1S), which in turn can be converted into estrone and estradiol.<ref name="Gregoire2013">{{cite book|author=A. T. Gregoire|title=Contraceptive Steroids: Pharmacology and Safety|url=https://books.google.com/books?id=7dnTBwAAQBAJ&pg=PA109|date=13 March 2013|publisher=Springer Science & Business Media|isbn=978-1-4613-2241-2|pages=109–}}</ref> Circulating concentrations of E2S are much lower than those of E1S.<ref name="KinclPasqualini2013" /> 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.<ref name="O'BrienBruce2009" /><ref name="Pasqualini2002" />

As the [[Sodium salts|sodium salt]] '''sodium estradiol sulfate''', E2S is present as a minor constituent (0.9%) of [[conjugated equine estrogen]]s (CEEs), or [[Premarin]].<ref name="FritzSperoff2012">{{cite book|author1=Marc A. Fritz|author2=Leon Speroff|title=Clinical Gynecologic Endocrinology and Infertility|url=https://books.google.com/books?id=KZLubBxJEwEC&pg=PA751|date=28 March 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-4847-3|pages=751–}}</ref> 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.<ref name="LauritzenStudd2005">{{cite book|author1=Christian Lauritzen|author2=John W. W. Studd|title=Current Management of the Menopause|url=https://books.google.com/books?id=WD7S7677xUUC&pg=PA364|date=22 June 2005|publisher=CRC Press|isbn=978-0-203-48612-2|pages=364–}}</ref><ref name="Huxtable2013">{{cite book|author=Ryan J. Huxtable|title=Biochemistry of Sulfur|url=https://books.google.com/books?id=5DfoBwAAQBAJ&pg=PA312|date=11 November 2013|publisher=Springer Science & Business Media|isbn=978-1-4757-9438-0|pages=312–}}</ref> Aside from its presence in CEEs, E2S is not available as a commercial [[pharmaceutical drug]].<ref name="KingGhosh2006">{{cite journal | first1=Roberta | last1=King | title=Inhibition of human phenol and estrogen sulfotransferase by certain non-steroidal anti-inflammatory agents | last2=Ghosh | first2=Anasuya | last3=Wu | first3=Jinfang | journal=Current Drug Metabolism | year=2006 | volume=7 | issue=7 | pages=745–753 | issn=1389-2002 | doi=10.2174/138920006778520615 | pmid=17073578 | pmc=2105742 }}</ref>

E2S shows about 10,000-fold lower [[potency (pharmacology)|potency]] in activating the [[estrogen receptor]]s relative to estradiol ''[[in vitro]]''.<ref name="pmid9294720">{{cite journal | vauthors = Coldham NG, Dave M, Sivapathasundaram S, McDonnell DP, Connor C, Sauer MJ | title = Evaluation of a recombinant yeast cell estrogen screening assay | journal = Environ. Health Perspect. | volume = 105 | issue = 7 | pages = 734–42 | date = July 1997 | pmid = 9294720 | pmc = 1470103 | doi = 10.1289/ehp.97105734 }}</ref> It is 10-fold less [[potency (pharmacology)|potent]] than [[estrone sulfate]] orally in terms of ''[[in vivo]]'' [[uterotrophic]] effect in rats.<ref name="pmid3065072">{{cite journal | vauthors = Bhavnani BR | title = The saga of the ring B unsaturated equine estrogens | journal = Endocr. Rev. | volume = 9 | issue = 4 | pages = 396–416 | date = November 1988 | pmid = 3065072 | doi = 10.1210/edrv-9-4-396 }}</ref> Estrogen sulfates like estradiol sulfate or estrone sulfate are about twice as [[potency (pharmacology)|potent]] as the corresponding free estrogens in terms of [[estrogen (medication)|estrogenic]] effect when given orally to rodents.<ref name="HerrRevesz1970">{{cite book|last1=Herr|first1=F.|last2=Revesz|first2=C.|last3=Manson|first3=A. J.|last4=Jewell|first4=J. B.|title=Chemical and Biological Aspects of Steroid Conjugation|chapter=Biological Properties of Estrogen Sulfates|year=1970|pages=368–408|doi=10.1007/978-3-642-95177-0_8|doi-broken-date=2024-11-02 |isbn=978-3-642-95179-4}}</ref> This in part led to the introduction of [[conjugated estrogens]] (Premarin), which are primarily estrone sulfate, in 1941.<ref name="HerrRevesz1970" />

Although inactive at [[steroid hormone receptor]]s, E2S has been found to act as a potent [[enzyme inhibitor|inhibitor]] of [[glutathione S-transferase]],<ref name="pmid9039952">{{cite journal | vauthors = Runge-Morris MA | title = Regulation of expression of the rodent cytosolic sulfotransferases | journal = FASEB J. | volume = 11 | issue = 2 | pages = 109–17 | year = 1997 | doi = 10.1096/fasebj.11.2.9039952 | doi-access = free | pmid = 9039952 | s2cid = 22112485 }}</ref> an [[enzyme]] that contributes to the inactivation of estradiol via conversion of it into an estradiol-[[glutathione]] [[conjugation (biochemistry)|conjugate]].<ref name="pmid9055636">{{cite journal | vauthors = Singh D, Pandey RS | title = Glutathione-S-transferase in rat ovary: its changes during estrous cycle and increase in its activity by estradiol-17 beta | journal = Indian J. Exp. Biol. | volume = 34 | issue = 11 | pages = 1158–60 | year = 1996 | pmid = 9055636 }}</ref> As such, E2S can indirectly serve as a positive effector of estrogen signaling.<ref name="pmid9039952" />

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&nbsp;times higher than those of estrone.<ref name="CowieForsyth1980">{{cite book|last1=Cowie|first1=Alfred T.|last2=Forsyth|first2=Isabel A.|last3=Hart|first3=Ian C.|title=Hormonal Control of Lactation|chapter=Growth and Development of the Mammary Gland|series=Monographs on Endocrinology|volume=15|year=1980|pages=58–145|issn=0077-1015|doi=10.1007/978-3-642-81389-4_3|pmid=6250026|isbn=978-3-642-81391-7}}</ref>

E2S at an oral dosage of 5&nbsp;mg/day in women resulted in inhibition of [[ovulation]] in 89% of cycles (47 of 53).<ref name="pmid4163201">{{cite journal | vauthors = Gual C, Becerra C, Rice-Wray E, Goldzieher JW | title = Inhibition of ovulation by estrogens | journal = Am J Obstet Gynecol | volume = 97 | issue = 4 | pages = 443–7 | date = February 1967 | pmid = 4163201 | doi = 10.1016/0002-9378(67)90555-8 }}</ref>

{{Affinities and estrogenic potencies of estrogen esters and ethers at the estrogen receptors}}

{{Structural properties of selected estradiol esters}}

== See also ==
* [[Catechol estrogen]]
* [[Dehydroepiandrosterone sulfate|DHEA sulfate]]
* [[Estradiol glucuronide]]
* [[Estriol sulfate]]
* [[Estrogen conjugate]]
* [[Lipoidal estradiol]]
* [[Pregnenolone sulfate]]
* [[List of estrogen esters#Estradiol esters|List of estrogen esters § Estradiol esters]]

== References ==
{{Reflist}}

{{Estradiol salts}}
{{Estradiol}}
{{Steroid hormones}}
{{Estrogens and antiestrogens}}
{{Estrogen receptor modulators}}

[[Category:Estradiol esters]]
[[Category:Human metabolites]]
[[Category:Phenol esters]]
[[Category:Sulfate esters]]