Vesicles and mixed micelles in hypothyroid rat bile before and after thyroid hormone treatment: evidence for a vesicle transport system for biliary cholesterol secretion.

Abstract

Hypothyroid rats show reduced secretion of biliary lipids, especially cholesterol. Secretion of biliary cholesterol is markedly augmented to levels above euthryroid beginning 12-24 h after administration of thyroid hormone. In the current studies, bile from hypothyroid and triiodothyronine-treated chronic bile-fistula rats was analyzed for vesicles and mixed micelles by metrizamide gradient ultracentrifugation. For euthryoid and hypothyroid animals, less than 12% of biliary cholesterol was in a vesicle gradient fraction. After treatment with triiodothyronine, biliary cholesterol increased markedly, and 50% of total cholesterol, 60% of excess cholesterol secreted, appeared in the vesicle fraction. Triiodothyronine stimulation of vesicle secretion resulted in cholesterol-rich vesicles (cholesterol:phospholipid ratio rose from less than 0.1 to 0.56), but no change in the distinct fatty acid composition of vesicle phospholipids. The microtubule inhibitor colchicine, given 12 h after triiodothyronine, prevented subsequent increase in cholesterol secretion in the form of vesicles. These studies, in a model that allows rapid changes in biliary lipid secretion, support the hypothesis that an important component of cholesterol and phospholipid secretion into bile involves microtubules and may involve a vesicle pathway.