Estradiol sulfate - Wiki slovník

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-cyclopentaphenanthren-7-yl hydrogen sulfate
	Other names Estra-1,3,5(10)-triene-3,17β-diol 3-sulfate
Identifiers
CAS Number	481-96-9; 4999-79-5 (sodium);
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:4866;
ChEMBL	ChEMBL1628111;
ChemSpider	59790;
PubChem CID	66416;
UNII	4NKQ3751P6;
CompTox Dashboard (EPA)	DTXSID30964000 ;
	InChI 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;
	SMILES CC12CCC3C(C1CCC2O)CCC4=C3C=CC(=C4)OS(=O)(=O)O;
Properties
Chemical formula	C18H24O5S
Molar mass	352.445 g/mol
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references

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]

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Affinities and estrogenic potencies of estrogen esters and ethers at the estrogen receptors
Estrogen	Other names	RBATooltip Relative binding affinity (%)^a	REP (%)^b
Estrogen	Other names	ER	ERα	ERβ
Estradiol	E2	100	100	100
Estradiol 3-sulfate	E2S; E2-3S	?	0.02	0.04
Estradiol 3-glucuronide	E2-3G	?	0.02	0.09
Estradiol 17β-glucuronide	E2-17G	?	0.002	0.0002
Estradiol benzoate	EB; Estradiol 3-benzoate	10	1.1	0.52
Estradiol 17β-acetate	E2-17A	31–45	24	?
Estradiol diacetate	EDA; Estradiol 3,17β-diacetate	?	0.79	?
Estradiol propionate	EP; Estradiol 17β-propionate	19–26	2.6	?
Estradiol valerate	EV; Estradiol 17β-valerate	2–11	0.04–21	?
Estradiol cypionate	EC; Estradiol 17β-cypionate	?^c	4.0	?
Estradiol palmitate	Estradiol 17β-palmitate	0	?	?
Estradiol stearate	Estradiol 17β-stearate	0	?	?
Estrone	E1; 17-Ketoestradiol	11	5.3–38	14
Estrone sulfate	E1S; Estrone 3-sulfate	2	0.004	0.002
Estrone glucuronide	E1G; Estrone 3-glucuronide	?	<0.001	0.0006
Ethinylestradiol	EE; 17α-Ethynylestradiol	100	17–150	129
Mestranol	EE 3-methyl ether	1	1.3–8.2	0.16
Quinestrol	EE 3-cyclopentyl ether	?	0.37	?
Footnotes: ^a = Relative binding affinities (RBAs) were determined via in-vitro displacement of labeled estradiol from estrogen receptors (ERs) generally of rodent uterine cytosol. Estrogen esters are variably hydrolyzed into estrogens in these systems (shorter ester chain length -> greater rate of hydrolysis) and the ER RBAs of the esters decrease strongly when hydrolysis is prevented. ^b = Relative estrogenic potencies (REPs) were calculated from half-maximal effective concentrations (EC₅₀) that were determined via in-vitro β‐galactosidase (β-gal) and green fluorescent protein (GFP) production assays in yeast expressing human ERα and human ERβ. Both mammalian cells and yeast have the capacity to hydrolyze estrogen esters. ^c = The affinities of estradiol cypionate for the ERs are similar to those of estradiol valerate and estradiol benzoate (figure). Sources: See template page.

v
t
e
Structural properties of selected estradiol esters
Estrogen	Structure	Ester(s)				Relative mol. weight	Relative E2 content^b	log P^c
Estrogen	Structure	Position(s)	Moiet(ies)	Type	Length^a	Relative mol. weight	Relative E2 content^b	log P^c
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	–	1.23^f	0.81^f	2.9^g
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.

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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čítajte viac o Estradiol_sulfate

[KinclPasqualini2013-1] 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.

[O'BrienBruce2009-2] 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.

[WangJames2005-3] 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.

[Pasqualini2002-4] Jorge R. Pasqualini (17 July 2002). Breast Cancer: Prognosis, Treatment, and Prevention. CRC Press. pp. 195–. ISBN 978-0-203-90924-9.

[HumansOrganization2007-5] 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.

[LeclercqToma2012-6] 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.

[Gregoire2013-7] A. T. Gregoire (13 March 2013). Contraceptive Steroids: Pharmacology and Safety. Springer Science & Business Media. pp. 109–. ISBN 978-1-4613-2241-2.

[FritzSperoff2012-8] Marc A. Fritz; Leon Speroff (28 March 2012). Clinical Gynecologic Endocrinology and Infertility. Lippincott Williams & Wilkins. pp. 751–. ISBN 978-1-4511-4847-3.

[LauritzenStudd2005-9] Christian Lauritzen; John W. W. Studd (22 June 2005). Current Management of the Menopause. CRC Press. pp. 364–. ISBN 978-0-203-48612-2.

[Huxtable2013-10] Ryan J. Huxtable (11 November 2013). Biochemistry of Sulfur. Springer Science & Business Media. pp. 312–. ISBN 978-1-4757-9438-0.

[KingGhosh2006-11] 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.

[pmid9294720-12] 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.

[pmid3065072-13] 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.

[HerrRevesz1970-14] 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 (inactive 2024-03-25). ISBN 978-3-642-95179-4.{{cite book}}: CS1 maint: DOI inactive as of March 2024 (link)

[pmid9039952-15] 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.

[pmid9055636-16] 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.

[CowieForsyth1980-17] 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.

[pmid4163201-18] 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.

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v t e Estradiol
Topics	Estradiol (as a hormone) Estradiol (as a medication) Pharmacodynamics of estradiol Pharmacokinetics of estradiol Estrogen (as a hormone) Estrogen (as a medication) Menopausal hormone therapy Feminizing hormone therapy Estradiol-containing birth control pill Combined injectable birth control High-dose estrogen Hydroxylation of estradiol
Esters	Estradiol acetate Estradiol acetylsalicylate Estradiol anthranilate Estradiol benzoate butyrate Estradiol benzoate cyclooctenyl ether Estradiol benzoate Estradiol butyrylacetate Estradiol cyclooctyl acetate Estradiol cypionate Estradiol decanoate Estradiol diacetate Estradiol dibutyrate Estradiol dienantate Estradiol dipropionate Estradiol distearate Estradiol disulfate Estradiol diundecylate Estradiol diundecylenate Estradiol enantate Estradiol furoate Estradiol glucuronide Estradiol hemisuccinate Estradiol hexahydrobenzoate Estradiol monopropionate Estradiol mustard Estradiol palmitate Estradiol phenylpropionate Estradiol phosphate Estradiol pivalate Estradiol propoxyphenylpropionate Estradiol salicylate Estradiol stearate Estradiol sulfamate Estradiol sulfate Estradiol undecylate Estradiol undecylenate Estradiol valerate Estramustine phosphate (estradiol normustine phosphate) Estrogen ester Polyestradiol phosphate
Related	Estrone Estriol Estetrol Ethinylestradiol Conjugated estrogens Esterified estrogens Estrone sulfate Estropipate (piperazine estrone sulfate)

See also

References