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Thyroid dysfunction, either hyper or hypothyroidism, promotes gallstone formation by different mechanisms

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2016年第7期17卷 515-525页

作者： Yong WANG Xing YU Qun-zi ZHAO Shu ZHENG Wen-jie QING chun-di MIAO Jaiswal SANJAY Department of Thyroid Surgery the Second Affiliated Hospital School of Medicine Zhejiang University cancer Institute the Second Affiliated Hospital School of Medicine Zhejiang University Department of clinical Medicine School of Medicine Zhejiang University

We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male c57BL/6 mice were randomly distributed into three groups each of which received an intervention to induce hyperthyroidism, hypothyroidism, or euthyroidism. After 5 weeks of feeding a lithogenic diet of 15% （w/w） butter fat, 1% （w/w） cholesterol, and 0.5% （w/w） cholic acid, mice were killed for further experiments. The incidence of cholesterol monohydrate crystal formation was 100% in mice with hyperthyroidism, 83% in hypothyroidism, and 33% in euthyroidism, the differences being statistically significant. Among the hepatic lithogenic genes, Tr~ was found to be up-regulated and Rxr down-regulated in the mice with hypothyroidism. In contrast, Lxra, Rxr, and cyp7al were up-regulated and Fxr down-regulated in the mice with hyperthyroidism. In conclusion, thyroid dysfunction, either hyperthyroidism or hypothyroidism, promotes the formation of cholesterol gallstones in c57BL/6 mice. Gene expression differences suggest that thyroid hormone disturbance leads to gallstone formation in different ways. Hyperthyroidism induces cholesterol gallstone formation by regulating expression of the hepatic nuclear receptor genes such as Lxra and Rxr, which are significant in cholesterol metabolism pathways. However, hypothyroidism induces cholesterol gallstone formation by promoting cholesterol biosynthesis.

关键词： Hypothyroidism Hyperthyroidism cholesterol gallstone c57bw6 mice Hepatic lithogenic genes

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