These authors contributed equally to this study.
A novel role for thyroid-stimulating hormone: Up-regulation of hepatic 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase expression through the cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate–responsive element binding protein pathway†
Article first published online: 11 JUN 2010
Copyright © 2010 American Association for the Study of Liver Diseases
Volume 52, Issue 4, pages 1401–1409, October 2010
How to Cite
Tian, L., Song, Y., Xing, M., Zhang, W., Ning, G., Li, X., Yu, C., Qin, C., Liu, J., Tian, X., Sun, X., Fu, R., Zhang, L., Zhang, X., Lu, Y., Zou, J., Wang, L., Guan, Q., Gao, L. and Zhao, J. (2010), A novel role for thyroid-stimulating hormone: Up-regulation of hepatic 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase expression through the cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate–responsive element binding protein pathway. Hepatology, 52: 1401–1409. doi: 10.1002/hep.23800
Potential conflict of interest: Nothing to report.
- Issue published online: 11 JUN 2010
- Article first published online: 11 JUN 2010
- Manuscript Accepted: 2 JUN 2010
- Manuscript Received: 25 MAR 2010
- Supported by the Natural Science Foundation of China (30971409) and the Natural Science Foundation of Shandong Province ZR2009CZ009
Elevated thyroid-stimulating hormone (TSH) and hypercholesterolemia commonly coexist, as typically seen in hypothyroidism, but there is no known mechanism directly linking the two. Here, we demonstrated that in liver cells, TSH promoted the expression of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR), a rate-limiting enzyme in cholesterol synthesis, by acting on the TSH receptor in hepatocyte membranes and stimulating the cyclic adenosine monophosphate / protein kinase A / cyclic adenosine monophosphate–responsive element binding protein (cAMP/PKA/CREB) signaling system. In thyroidectomized rats, the production of endogenous thyroid hormone was eliminated and endogenous TSH was suppressed through pituitary suppression with constant administration of exogenous thyroid hormone, and hepatic HMGCR expression was increased by administration of exogenous TSH. These results suggested that TSH could up-regulate hepatic HMGCR expression, which indicated a potential mechanism for hypercholesterolemia involving direct action of TSH on the liver. (HEPATOLOGY 2010)