Reversal of progesterone-induced biliary cholesterol output by dietary cholesterol and ethynylestradiol

The significant increment of biliary cholesterol output induced by the subcutaneous injection of 40 mg/kg body wt. of progesterone to male rats was reversed either by feeding a 1% cholesterol diet or by injecting three daily doses of 2 mg/kg ethynylestradiol. These last two experimental manipulations significantly decreased biliary cholesterol saturation from 44 +/- 4% (progesterone) to 30 +/- 3% (progesterone +1% cholesterol diet) and 23 +/- 0.5% (progesterone + ethynylestradiol) under circumstances of minor changes in the rates of biliary bile salt and phospholipids outputs. The rate of the microsomal acyl-CoA:cholesterol acyltransferase and the concentration of microsomal cholesterol esters significantly increased more than 100% in both cholesterol-fed and estradiol-injected rats. The rate of biliary cholesterol output was reciprocally correlated with both microsomal cholesterol ester concentration of livers (r = -0.47, P less than 0.01) and the activity of the hepatic acyl-CoA:cholesterol acyltransferase (r = -0.58, P less than 0.005) in a series of rats injected with progesterone, with progesterone +1% cholesterol diet and with progesterone + estradiol. No correlation was found between the rate of biliary cholesterol output and the concentration of microsomal free cholesterol. These experiments demonstrate the existence of a close and reciprocal relationship between the rate of biliary cholesterol output and the rate at which the liver esterifies cholesterol.