Y. Chico et al., REGULATION OF BILE-ACID SYNTHESIS BY ESTRADIOL AND PROGESTERONE IN PRIMARY CULTURES OF RAT HEPATOCYTES, EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, 104(2), 1996, pp. 137-144
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.