Journal of Lipid Research, Vol 33, 1467-1473, Copyright © 1992 by Lipid Research, Inc.
Thyroid hormone differentially augments biliary sterol secretion in the rat. II. The chronic bile fistula model
RL Gebhard and WF Prigge
VA Medical Center, Minneapolis, MN 55417.
To further define thyroid hormone effects on bile acid synthesis and
biliary lipid secretion, studies were done in chronic bile fistula rats.
Euthyroid and methimazole-hypothyroid rats, with and without
triiodothyronine (T3) injection, had total bile diversion for timed bile
collections. With interrupted enterohepatic circulation, cholesterol
absorption is negligible and bile acid secretion equals bile acid synthesis
rate. Hypothyroid rats had diminished levels of bile acid synthesis and
biliary secretion of cholesterol and phospholipid. Single dose T3 injection
produced a 13-fold increase in bile cholesterol secretion and a 3-fold
increase in phospholipid secretion, both initiated 12 h after T3. Bile acid
synthesis increased by 50%, but the increase did not begin until 24 h after
T3. Neither hypothyroidism nor T3 treatment abolished diurnal rhythms of
bile acid synthesis and biliary lipid secretion. Inhibition of cholesterol
synthesis with lovastatin resulted in a persistent 33% decrease in bile
acid synthesis in euthyroid and hypothyroid rats, while bile cholesterol
secretion only transiently decreased. Inhibition of cholesterol synthesis
did not alter T3-induced bile cholesterol secretion, with a 10-fold
increase seen. However, bile acid synthesis was not stimulated by T3 in the
presence of lovastatin. We conclude that facilitated bile acid synthesis
and biliary cholesterol secretion are early effects of T3 and may account
for the hypocholesterolemia of T3. Cholesterol synthesis does not appear to
be required for the T3- induced bile cholesterol secretion.