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.
Estradiol 17-(β-D-Glucuronide)是雌二醇(一种主要的女性性激素)经过代谢形成的产物。在人体内,雌二醇可以通过与葡萄糖醛酸结合的方式形成雌二醇葡萄糖醛酸化物,即Estradiol 17-(β-D-Glucuronide)。Estradiol 17-(β-D-Glucuronide)是有机阴离子转运多肽家族(Oatp)和多药耐药蛋白(Mrp2)的底物[1]。Estradiol 17-(β-D-Glucuronide)可诱导胆汁淤积[2]。
在体外,Estradiol 17-(β-D-Glucuronide) 200µM处理大鼠肝细胞20 min可诱导 小管转运蛋白Abcc2功能损伤和内吞内化[3]。
在体内,Estradiol 17-(β-D-Glucuronide) (15 µmol/kg; i.v.) 会损害雌性SD大鼠胆盐(BS)输出,诱导胆盐输出泵(Bsep)内化[4]。 Estradiol 17-(β-D-Glucuronide)可抑制大鼠胆汁流动,在8.5至21 µmol/kg 静脉注射范围内对胆汁淤积程度具有剂量依赖性,11 µmol/kg 的剂量给药后15 -30分钟内使胆汁酸分泌率下降了近70%[5]。