Ethinylestradiol administration selectively alters liver sinusoidal membrane lipid fluidity and protein composition

Abstract

Administration of high-dose ethinylestradiol to rats decreases bile flow, Na,K-ATPase specific activity, and liver plasma membrane fluidity. By use of highly purified sinusoidal and bile canalicular membrane fractions, the effect of ethinylestradiol administration on the protein and lipid composition and fluidity of plasma membrane fractions was examined. In sinusoidal fractions, ethinylestradiol (EE) administration decreased Na,K-ATPase activity (32%) and increased activities of alkaline phosphatase (254%), Mg2+-ATPase (155%), and a 160-kDa polypeptide (10-fold). Steady-state and dynamic fluorescence polarization was used to study membrane lipid structure. Steady-state polarization of diphenylhexatriene (DPH) was significantly higher in canalicular compared to sinusoidal membrane fractions. Ethinylestradiol (5 mg/kg per day for 5 days) selectively increased sinusoidal polarization values. Similar changes were demonstrated with the probes 2- and 12-anthroyloxystearate. Time-resolved fluorescence polarization measurements indicated that EE administration for 5 days did not change DPH lifetime but increased the order component (r infinity) and decreased the rotation rate (R). However, 1 and 3 days after EE administration and with low doses (10-100 micrograms/kg per day for 5 days) the Na,K-ATPase, bile flow, and order component were altered, but the rotation rate was unchanged. Vesicles prepared from total sinusoidal membrane lipids of EE-treated rats, as well as phospholipid vesicles, demonstrated increased DPH polarization, as did intact plasma membrane fractions. Liver plasma membrane fractions showed no change in free cholesterol or cholesterol/phospholipid molar ratio, while esterified cholesterol content was increased with high-dose but not low-dose ethinylestradiol.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of estrogen on scavenger receptor BI expression in the rat

“…The influx of cholesterol into the liver with estrogen treatment alters membrane morphology and fluidity (Rosario et al 1988). Normally, the sinusoidal membrane surface has an extensive array of microvillar extensions.…”

Ezrin-radixin-moesin–binding phosphoprotein 50 is expressed at the apical membrane of rat liver epithelia

“…Membrane preparations enriched in canalicular and sinusoidal membranes were prepared as previously described. 31 Briefly, rat livers were homogenized (300 mmol/L mannitol, 5 mmol/L EGTA, 18 mmol/L Tris-HCL, 0.1 mmol/L PMSF; pH 7.4) and centrifuged (48,000 g for 30 min). The pellet was resuspended and Mg 2ϩ precipitated (15 mmol/L MgCl 2 ; 2,450 g for 15 min).…”

Bezafibrate stimulates canalicular localization of NBD-labeled PC in HepG2 cells by PPARα-mediated redistribution of ABCB4

“…This protects the biliary epithelium from the detergent action of hydrophobic bile acids (1), which are present at high concentrations in the biliary tree (2,3).…”