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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
Author(s) -
Tian Limin,
Song Yongfeng,
Xing Mingzhao,
Zhang Wei,
Ning Guang,
Li Xiaoying,
Yu Chunxiao,
Qin Chengkong,
Liu Jun,
Tian Xingsong,
Sun Xianglan,
Fu Rui,
Zhang Lin,
Zhang Xiujuan,
Lu Yan,
Zou Jianwen,
Wang Laicheng,
Guan Qingbo,
Gao Ling,
Zhao Jiajun
Publication year - 2010
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23800
Subject(s) - medicine , endocrinology , adenosine , thyroid stimulating hormone , cyclic adenosine monophosphate , protein kinase a , creb , hormone , adenosine monophosphate , reductase , chemistry , biology , kinase , enzyme , receptor , biochemistry , transcription factor , gene
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. (H EPATOLOGY 2010)