estriol glucuronide

{{Short description|Chemical compound}}

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| IUPAC_name = (2S,3S,4S,5R,6R)-6-[[(8R,9S,13S,14S,16R,17R)-3,17-dihydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-16-yl]oxy]-3,4,5-trihydroxyoxane-2-carboxylic acid

| image = Estriol glucuronide.svg

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| routes_of_administration = By mouth

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| CAS_number = 28808-07-3

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| PubChem = 122281

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| ChemSpiderID = 134818

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| synonyms = Estriol glucuronidate; (16α,17β)-16,17-Dihydroxyestra-1,3,5(10)-trien-3-yl D-glucopyranosiduronic acid; β-D-Glucopyranuronic acid, monoglycoside with (16α,17β)-estra-1,3,5(10)-triene-3,16,17-triol

| C=24 | H=32 | O=9

| SMILES = C[C@]12CC[C@H]3[C@H]([C@@H]1C[C@H]([C@@H]2O)O[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)C(=O)O)O)O)O)CCC5=C3C=CC(=C5)O

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| StdInChI = InChI=1S/C24H32O9/c1-24-7-6-13-12-5-3-11(25)8-10(12)2-4-14(13)15(24)9-16(21(24)29)32-23-19(28)17(26)18(27)20(33-23)22(30)31/h3,5,8,13-21,23,25-29H,2,4,6-7,9H2,1H3,(H,30,31)/t13-,14-,15+,16-,17+,18+,19-,20+,21+,23-,24+/m1/s1

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| StdInChIKey = FQYGGFDZJFIDPU-JRSYHJKYSA-N

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Estriol glucuronide (E3G), or oestriol glucuronide, also known as estriol monoglucuronide, as well as estriol 16α-β-D-glucosiduronic acid, is a natural, steroidal estrogen and the glucuronic acid (β-D-glucopyranuronic acid) conjugate of estriol.{{cite book| vauthors = Hill RA, Makin HL, Kirk DN, Murphy GM |title=Dictionary of Steroids|url=https://books.google.com/books?id=AI7EnUyeEtUC&pg=PA274|date=23 May 1991|publisher=CRC Press|isbn=978-0-412-27060-4|pages=274–}}{{cite journal | vauthors = Hashimoto Y, Neeman M | title = Isolation and characterization of estriol 16 alpha-glucosiduronic acid from human pregnancy urine | journal = The Journal of Biological Chemistry | volume = 238 | issue = 4 | pages = 1273–1282 | date = April 1963 | pmid = 14010351 | doi = 10.1016/S0021-9258(18)81175-9 | doi-access = free }} It occurs in high concentrations in the urine of pregnant women as a reversibly formed metabolite of estriol. Estriol glucuronide is a prodrug of estriol,{{cite book| vauthors = Smith RL, Williams RT | chapter = Implication of the Conjugation of Drug and Other Exogenous Substances | veditors = Dutton G |title=Glucuronic Acid Free and Combined: Chemistry, Biochemistry, Pharmacology, and Medicine| chapter-url = https://books.google.com/books?id=wo5M1g9pjcMC&pg=PA466|date=2 December 2012|publisher=Elsevier|isbn=978-0-323-14398-1|pages= 457–492 (466) }} and was the major component of Progynon and Emmenin, estrogenic products manufactured from the urine of pregnant women that were introduced in the 1920s and 1930s and were the first orally active estrogens.{{cite book| vauthors = Rooke T | chapter = Chapter 3: Life after the Thyroid |title=The Quest for Cortisone| chapter-url = https://books.google.com/books?id=70vvFrtpePoC&pg=PT54|date=1 January 2012|publisher=MSU Press|isbn=978-1-60917-326-5|pages=54–}}{{cite book | vauthors = Li A | chapter = Marketing Menopause: Science and the Public Relations of Premarin | jstor = j.ctt7zxvb.10 | veditors = Feldberg GD |title=Women, Health and Nation: Canada and the United States Since 1945|chapter-url=https://books.google.com/books?id=CRjtHlq1INcC&pg=PA103|year=2003|publisher=McGill-Queen's Press - MQUP|isbn=978-0-7735-2501-6|pages=103–}} Emmenin was succeeded by Premarin (conjugated equine estrogens), which is sourced from the urine of pregnant mares and was introduced in 1941.{{cite book | vauthors = Crook D | chapter = Estrogens used in current menopause therapies | veditors = Panay N, Briggs P, Kovacs G |title=Managing the Menopause| chapter-url=https://books.google.com/books?id=l0pLCgAAQBAJ&pg=PA118|date=20 August 2015|publisher=Cambridge University Press|isbn=978-1-107-45182-7|pages=118–123 }} Premarin replaced Emmenin because it was easier and less expensive to produce.

Estrogen glucuronides can be deglucuronidated into the corresponding free estrogens by β-glucuronidase in tissues that express this enzyme, such as the mammary gland.{{cite journal | vauthors = Zhu BT, Conney AH | title = Functional role of estrogen metabolism in target cells: review and perspectives | journal = Carcinogenesis | volume = 19 | issue = 1 | pages = 1–27 | date = January 1998 | pmid = 9472688 | doi = 10.1093/carcin/19.1.1 | doi-access = free }} As a result, estrogen glucuronides have estrogenic activity via conversion into estrogens.

The positional isomer of estriol 16α-glucuronide, estriol 3-glucuronide, also occurs as an endogenous metabolite of estriol, although to a much lower extent in comparison.{{Cite web | vauthors = Wishart DS, Guo A, Oler E, Wang F, Anjum A, Peters H, Dizon R, Sayeeda Z, Tian S, Lee BL, Berjanskii M, Mah R, Yamamoto M, Jovel J, Torres-Calzada C, Hiebert-Giesbrecht M, Lui VW, Varshavi D, Varshavi D, Allen D, Arndt D, Khetarpal N, Sivakumaran A, Harford K, Sanford S, Yee K, Cao X, Budinski Z, Liigand J, Zhang L, Zheng J, Mandal R, Karu N, Dambrova M, Schiöth HB, Greiner R, Gautam V | display-authors = 6 |url=http://www.hmdb.ca/metabolites/HMDB10335| work = Human Metabolome Database | title = Metabocard for Estriol-3-glucuronide | id = HMDB0010335 }}{{cite book | vauthors = Oettel M, Schillinger E, Kuhnz W, Blode H, Zimmermann H | chapter = Pharmacokinetics of Exogenous Natural and Synthetic Estrogens and Antiestrogens | series = Handbook of Experimental Pharmacology | veditors = Oettel M, Schillinger E |title=Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen| chapter-url = https://books.google.com/books?id=wBvyCAAAQBAJ&pg=PA265|date=6 December 2012| volume = 135 / 2 |publisher=Springer Science & Business Media|isbn=978-3-642-60107-1|pages=261-322 (265) | doi = 10.1007/978-3-642-60107-1_15 }}{{cite journal | vauthors = Musey PI, Kirdani RY, Bhanalaph T, Sandberg AA | title = Estriol metabolism in the baboon: analysis of urinary and biliary metabolites | journal = Steroids | volume = 22 | issue = 6 | pages = 795–817 | date = December 1973 | pmid = 4203562 | doi = 10.1016/0039-128X(73)90054-8 }}