REGULATION OF BILE-ACID SYNTHESIS BY ESTRADIOL AND PROGESTERONE IN PRIMARY CULTURES OF RAT HEPATOCYTES

We have used primary monolayer cultures of hepatocytes from rats fed s tandard and cholestyramine-diet to study the effects of 17 beta-estrad iol and progesterone on the activity of cholesterol 7 alpha-hydroxylas e (EC 1.14.13.17) and bile acid synthesis. Cholesterol 7 alpha-hydroxy lase activity in hepatocytes freshly isolated from rats fed either die t mentioned above declined gradually during attachment and the first d ay of culture. Exposure of cell monolayers to 1 or 10 mu M estradiol o r progesterone resulted in rapid and transient increases in cholestero l 7 alpha-hydroxylase activity, the maximal stimulation of enzyme acti vity being observed after a 6 h culture period. Bile acid synthesis in standard cells was markedly activated by both hormones, but in choles tyramine cells only the effect caused by 10 mu M progesterone was sign ificant. The cellular content of total bile acids was not significantl y altered by the presence of the hormones, except by 10 mu M progester one, which provoked an initial cellular depletion of bile acids that w as rapidly restored. Bile acid output was enhanced by treating primary cultures with 10 mu M estradiol or progesterone, but whereas the incr eases caused by progesterone were marked and sustained, those caused b y estradiol were minor and transient. We conclude that progesterone an d 17 beta-estradiol, in this order of potency, enhance short-term bile acid synthesis in rat hepatocyte monolayers.