Vesicles and mixed micelles in hypothyroid rat bile before and after thyroid hormone treatment: evidence for a vesicle transport system for biliary cholesterol secretion.
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.
Andreini
J P
JP
Department of Medicine, Minneapolis Veterans Affairs Medical Center, MN 55417.
Prigge
W F
WF
Ma
C
C
Gebbard
R L
RL
D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D005227:Fatty Acids / Q000032:analysis; D007037:Hypothyroidism / Q000378:metabolism*; D008297:Male; D008823:Micelles; D008862:Microsomes, Liver / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology
D005227:Fatty Acids; D008823:Micelles; D010743:Phospholipids; D013963:Thyroid Hormones; D014284:Triiodothyronine; D002784:Cholesterol