Estriol glucuronide

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.^[1][2] It occurs in high concentrations in the urine of pregnant women as a reversibly formed metabolite of estriol.^[2] Estriol glucuronide is a prodrug of estriol,^[3] 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.^[4][5] Emmenin was succeeded by Premarin (conjugated equine estrogens), which is sourced from the urine of pregnant mares and was introduced in 1941.^[4][5][6] Premarin replaced Emmenin because it was easier and less expensive to produce.^[4][5]

Estriol glucuronide

Clinical data
Other names	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
Routes of administration	By mouth
Identifiers
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
CAS Number	28808-07-3
PubChem CID	122281
ChemSpider	134818
CompTox Dashboard (EPA)	DTXSID30939935
ECHA InfoCard	100.161.795
Chemical and physical data
Formula	C24H32O9
Molar mass	464.511 g·mol−1
3D model (JSmol)	Interactive image
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
InChI InChI=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 Key:FQYGGFDZJFIDPU-JRSYHJKYSA-N

Estrogen glucuronides can be deglucuronidated into the corresponding free estrogens by β-glucuronidase in tissues that express this enzyme, such as the mammary gland.^[7] As a result, estrogen glucuronides have estrogenic activity via conversion into estrogens.^[7]

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.^[8][9][10]

See also

• Catechol estrogen
• Estradiol glucuronide
• Estradiol sulfate
• Estrogen conjugate
• Estrone glucuronide
• Estrone sulfate
• Lipoidal estradiol

References

1. Hill RA, Makin HL, Kirk DN, Murphy GM (23 May 1991). Dictionary of Steroids. CRC Press. pp. 274–. ISBN 978-0-412-27060-4.
2. Hashimoto Y, Neeman M (April 1963). "Isolation and characterization of estriol 16 alpha-glucosiduronic acid from human pregnancy urine". The Journal of Biological Chemistry. 238 (4): 1273–1282. doi:10.1016/S0021-9258(18)81175-9. PMID 14010351.
3. Smith RL, Williams RT (2 December 2012). "Implication of the Conjugation of Drug and Other Exogenous Substances". In Dutton G (ed.). Glucuronic Acid Free and Combined: Chemistry, Biochemistry, Pharmacology, and Medicine. Elsevier. pp. 457–492 (466). ISBN 978-0-323-14398-1.
4. Rooke T (1 January 2012). "Chapter 3: Life after the Thyroid". The Quest for Cortisone. MSU Press. pp. 54–. ISBN 978-1-60917-326-5.
5. Li A (2003). "Marketing Menopause: Science and the Public Relations of Premarin". In Feldberg GD (ed.). Women, Health and Nation: Canada and the United States Since 1945. McGill-Queen's Press - MQUP. pp. 103–. ISBN 978-0-7735-2501-6. JSTOR j.ctt7zxvb.10.
6. Crook D (20 August 2015). "Estrogens used in current menopause therapies". In Panay N, Briggs P, Kovacs G (eds.). Managing the Menopause. Cambridge University Press. pp. 118–123. ISBN 978-1-107-45182-7.
7. Zhu BT, Conney AH (January 1998). "Functional role of estrogen metabolism in target cells: review and perspectives". Carcinogenesis. 19 (1): 1–27. doi:10.1093/carcin/19.1.1. PMID 9472688.
8. Wishart DS, Guo A, Oler E, Wang F, Anjum A, Peters H, et al. "Metabocard for Estriol-3-glucuronide". Human Metabolome Database. HMDB0010335.
9. Oettel M, Schillinger E, Kuhnz W, Blode H, Zimmermann H (6 December 2012). "Pharmacokinetics of Exogenous Natural and Synthetic Estrogens and Antiestrogens". In Oettel M, Schillinger E (eds.). Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Handbook of Experimental Pharmacology. Vol. 135 / 2. Springer Science & Business Media. pp. 261-322 (265). doi:10.1007/978-3-642-60107-1_15. ISBN 978-3-642-60107-1.
10. Musey PI, Kirdani RY, Bhanalaph T, Sandberg AA (December 1973). "Estriol metabolism in the baboon: analysis of urinary and biliary metabolites". Steroids. 22 (6): 795–817. doi:10.1016/0039-128X(73)90054-8. PMID 4203562.

External links

• Metabocard for Estradiol 17-Glucuronide - Human Metabolome Database