Estradiol 17-(β-D-Glucuronide) (sodium salt) (Synonyms: E217G,β-Estradiol 17-(β-D-Glucuronide),17β-Estradiol 17-(β-D-Glucuronide),17β-Oestradiol 17-(β-D-Glucuronide))

Estradiol 17-(β-D-Glucuronide) is a metabolic product of estradiol, the main female sex hormone. In the human body, estradiol can be combined with glucuronic acid to form estradiol glucuronide, namely Estradiol 17-(β-D-Glucuronide). Estradiol 17-(β-D-Glucuronide) is a substrate of the organic anion transporting peptide family (Oatp) and multidrug resistance protein (Mrp2)[1]. Estradiol 17-(β-D-Glucuronide) can induce cholestasis ^[2].

In vitro, treatment with 200µM Estradiol 17-(β-D-Glucuronide) for 20 minutes in rat hepatocytes can induce dysfunction and internalization of the canalicular transporter protein Abcc2 ^[3].

In vivo, Estradiol 17-(β-D-Glucuronide) (15 µmol/kg; i.v.) impairs bile salt (BS) output in female SD rats, inducing internalization of the bile salt export pump (Bsep) [4]. Estradiol 17-(β-D-Glucuronide) can inhibit rat bile flow, showing a dose-dependent effect on the degree of cholestasis within the intravenous dosage range of 8.5 to 21 µmol/kg. A dose of 11 µmol/kg administered over 15-30 minutes reduced the bile acid secretion rate by nearly 70% ^[5].

References:
[1] Huadong Sun, Lichuan Liu, and K. Sandy Pang.Increased Estrogen Sulfation of Estradiol 17β-D-Glucuronide in Metastatic Tumor Rat Livers[J]Journal of Pharmacology and Experimental Therapeutics . 2006. 319: 818-831.
[2] Zucchetti, AndrÉs E, Barosso I R , Boaglio A ,et al.Prevention of estradiol 17beta-D-glucuronide-induced canalicular transporter internalization by hormonal modulation of cAMP in rat hepatocytes.[J]. Molecular Biology of the Cell, 2011, 22(20):3902-3915.
[3] Barosso I R ,Zucchetti, AndrÉs E, Miszczuk G S ,et al. EGFR participates downstream of ERα in estradiol-17β-D-glucuronide-induced impairment of Abcc2 function in isolated rat hepatocyte couplets.[J]Archives of Toxicology, 2016, 90(4):891-903.
[4] Fernando A. Crocenzi,1Aldo D. Mottino, et al.Estradiol-17β-D-glucuronide induces endocytic internalization of Bsep in rats.[J]Am J Physiol Gastrointest Liver Physiol (285): 449-459, 2003.
[5] Meyers M, Slikker W, Pascoe G, Vore M. Characterization of cholestasis induced by estradiol-17 beta-D-glucuronide in the rat. J Pharmacol Exp Ther. 1980 Jul;214(1):87-93.