Abstract
Alteration of thyroid status affects cholesterol and bile acid metabolism. In the present study, dietary supplements of DL-thyroxine and propylthiouracil were used to modulate plasma thyroxine levels, plasma lipoproteins, bile acid composition, and gallstone formation in hamsters. Male Syrian hamsters (Lakeview strain) were fed a gallstone-inducing purified diet (5% butter, 0.4% cholesterol) or the same diet supplemented with 0.005% thyroxine or 0.05% propylthiouracil for 5 weeks. Thyroxine administration greatly increased plasma triiodothyroxine (total T
3) and thyroxine (total T
4), whereas propylthiouracil depressed both. Compared with the gallstone diet, plasma cholesterol and triglycerides were significantly elevated by thyroxine and depressed by propylthiouracil. On autopsy, three of 10 hamsters fed the gallstone diet had cholesterol gallstones. No cholesterol gallstones were found in hamsters treated with thyroxine, but 9 of 10 animals had pigment stones. By contrast, only one of 10 hamsters supplemented with propylthiouracil had cholesterol stones, whereas 9 of 10 were without any stones. The lithogenic index was significantly reduced with thyroxine (1.1 ± 0.4) compared with the gallstone diet (2.6 ± 0.7), while the lithogenic index in hamsters fed propylthiouracil was intermediate (1.8 ± 0.7). With the gallstone diet, the cheno pool was slightly larger than the cholate pool. Thyroxine resulted in three times more cholate than cheno (percent distribution), while propylthiouracil resulted in twice as much cheno as cholate. As a result the cholate to cheno ratio was tripled by thyroxine and reduced 40% by propylthiouracil compared with the gallstone diet. Thus, despite enhanced lipemia, thyroxine-treated hamsters were protected against cholesterol gallstones, possibly by their ability to maintain a predominantly cholate bile acid profile. On the other hand, propylthiouracil protected against gallstones of all types despite a high cheno profile and elevations in hydrophobicity index. These results indicate that cholesterol gallstone formation in hamsters does not depend solely on plasma hyperlipemia, the bile acid profile, or either the lithogenic index or hydrophobicity index.