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Estradiol sulfate
Names
IUPAC name
17β-Hydroxyestra-1,3,5(10)-trien-3-yl hydrogen sulfate
Systematic IUPAC name
(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
Other names
Estra-1,3,5(10)-triene-3,17β-diol 3-sulfate
Identifiers
ChEBI
ChEMBL
ChemSpider
UNII
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
Key: QZIGLSSUDXBTLJ-ZBRFXRBCSA-N
CC12CCC3C(C1CCC2O)CCC4=C3C=CC(=C4)OS(=O)(=O)O
Properties
C 18 H 24 O 5 S
Molar mass
352.445 g/mol
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
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]
Structural properties of selected estradiol esters
Estrogen
Structure
Ester(s)
Relative
mol. weight
Relative
E2 contentb
log Pc
Position(s)
Moiet(ies)
Type
Lengtha
Estradiol
–
–
–
–
1.00
1.00
4.0
Estradiol acetate
C3
Ethanoic acid
Straight-chain fatty acid
2
1.15
0.87
4.2
Estradiol benzoate
C3
Benzoic acid
Aromatic fatty acid
– (~4–5)
1.38
0.72
4.7
Estradiol dipropionate
C3, C17β
Propanoic acid (×2)
Straight-chain fatty acid
3 (×2)
1.41
0.71
4.9
Estradiol valerate
C17β
Pentanoic acid
Straight-chain fatty acid
5
1.31
0.76
5.6–6.3
Estradiol benzoate butyrate
C3, C17β
Benzoic acid ,
butyric acid
Mixed fatty acid
– (~6, 2)
1.64
0.61
6.3
Estradiol cypionate
C17β
Cyclopentylpropanoic acid
Cyclic fatty acid
– (~6)
1.46
0.69
6.9
Estradiol enanthate
C17β
Heptanoic acid
Straight-chain fatty acid
7
1.41
0.71
6.7–7.3
Estradiol dienanthate
C3, C17β
Heptanoic acid (×2)
Straight-chain fatty acid
7 (×2)
1.82
0.55
8.1–10.4
Estradiol undecylate
C17β
Undecanoic acid
Straight-chain fatty acid
11
1.62
0.62
9.2–9.8
Estradiol stearate
C17β
Octadecanoic acid
Straight-chain fatty acid
18
1.98
0.51
12.2–12.4
Estradiol distearate
C3, C17β
Octadecanoic acid (×2)
Straight-chain fatty acid
18 (×2)
2.96
0.34
20.2
Estradiol sulfate
C3
Sulfuric acid
Water-soluble conjugate
–
1.29
0.77
0.3–3.8
Estradiol glucuronide
C17β
Glucuronic acid
Water-soluble conjugate
–
1.65
0.61
2.1–2.7
Estramustine phosphate d
C3, C17β
Normustine ,
phosphoric acid
Water-soluble conjugate
–
1.91
0.52
2.9–5.0
Polyestradiol phosphate e
C3–C17β
Phosphoric acid
Water-soluble conjugate
–
1.23f
0.81f
2.9g
Footnotes: a = Length of
ester in
carbon
atoms for
straight-chain fatty acids or approximate length of ester in carbon atoms for
aromatic or
cyclic fatty acids. b = Relative estradiol content by weight (i.e., relative
estrogenic exposure). c = Experimental or predicted
octanol/water partition coefficient (i.e.,
lipophilicity /
hydrophobicity ). Retrieved from
PubChem ,
ChemSpider , and
DrugBank . d = Also known as estradiol normustine phosphate . e =
Polymer of
estradiol phosphate (~13
repeat units ). f = Relative molecular weight or estradiol content per repeat unit. g = log P of repeat unit (i.e., estradiol phosphate). Sources: See individual articles.
See also
References
^
a
b 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 .
^
a
b
c
d 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 .
^ 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 .
^
a
b Jorge R. Pasqualini (17 July 2002).
Breast Cancer: Prognosis, Treatment, and Prevention . CRC Press. pp. 195–.
ISBN
978-0-203-90924-9 .
^
a
b 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 .
^ 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 .
^ A. T. Gregoire (13 March 2013).
Contraceptive Steroids: Pharmacology and Safety . Springer Science & Business Media. pp. 109–.
ISBN
978-1-4613-2241-2 .
^ Marc A. Fritz; Leon Speroff (28 March 2012).
Clinical Gynecologic Endocrinology and Infertility . Lippincott Williams & Wilkins. pp. 751–.
ISBN
978-1-4511-4847-3 .
^ Christian Lauritzen; John W. W. Studd (22 June 2005).
Current Management of the Menopause . CRC Press. pp. 364–.
ISBN
978-0-203-48612-2 .
^ Ryan J. Huxtable (11 November 2013).
Biochemistry of Sulfur . Springer Science & Business Media. pp. 312–.
ISBN
978-1-4757-9438-0 .
^ 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 .
^ 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 .
^ 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 .
^
a
b 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 (inactive 2024-03-25).
ISBN
978-3-642-95179-4 . {{
cite book }}
: CS1 maint: DOI inactive as of March 2024 (
link )
^
a
b 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 .
^ 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 .
^ Cowie, Alfred T.; Forsyth, Isabel A.; Hart, Ian C. (1980). "Growth and Development of the Mammary Gland". Hormonal Control of Lactation . Monographs on Endocrinology. Vol. 15. pp. 58–145.
doi :
10.1007/978-3-642-81389-4_3 .
ISBN
978-3-642-81391-7 .
ISSN
0077-1015 .
PMID
6250026 .
^ 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 .
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