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.

Limin Tian, Yongfeng Song, Mingzhao Xing, Wei Zhang, Guang Ning, Xiaoying Li, Chunxiao Yu, Chengkong Qin, Jun Liu, Xingsong Tian, Xianglan Sun, Rui Fu, Lin Zhang, Xiujuan Zhang, Yan Lu, Jianwen Zou, Laicheng Wang, Qingbo Guan, Ling Gao, Jiajun Zhao

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1401-1409
Number of pages9
JournalHepatology (Baltimore, Md.)
Volume52
Issue number4
StatePublished - Oct 2010
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology

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