Gastric estradiol-17β (E2) and liver ERα correlate with serum E2 in the cholestatic male rat

Abstract

Cholestasis is associated with changes in hepatic cholesterol metabolism and serum estrogen levels. Ueyama and colleagues reported that the gastric estradiol-17β (E2) level in the portal vein is several times higher than that in the artery. This study aimed to clarify the relationships between gastric E2, hepatic estrogen receptor (ER) α and cholesterol metabolism in cholestatic male rats induced by bile duct ligation (BDL). After BDL, serum E2 levels in the portal vein and artery were measured by ELISA. The gene expression of gastric estrogen-synthesizing enzymes and various hepatic enzymes for cholesterol metabolism were measured by real-time RT-PCR, and gastric aromatase and hepatic ERα proteins were determined by immunohistochemistry and western blotting. Portal E2 levels increased by 4.9, 5.0, and 3.6 times that of controls at 2 days after BDL (BDL2d), BDL4d, and BDL7d respectively. The change in arterial E2 levels was positively correlated with that in the portal vein. Under these conditions, the expression of hepatic Ers1 (ERα) mRNA and protein was significantly reduced in a negative correlation with serum E2 levels in the portal vein after BDL. The expression of hepatic male-specific cytochrome P450 (CYP) genes Cyp2c55 and Cyp3a2 decreased and female-specific Cyp2c12 increased after BDL. It is postulated that the increase in gastric E2 levels, which occurs after BDL, results in the reduction of hepatic ERα, the elevation of arterial E2 level and leads to cholesterol metabolism becoming sex steroid dependent.