title: 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.
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.
authors.affiliation: Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Tian
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Song
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Xing
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Yu
authors.forename: Chengkong
authors.initials: C
authors.lastname: Qin
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Xingsong
authors.initials: X
authors.lastname: Tian
authors.forename: Xianglan
authors.initials: X
authors.lastname: Sun
authors.forename: Rui
authors.initials: R
authors.lastname: Fu
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Jianwen
authors.initials: J
authors.lastname: Zou
authors.forename: Laicheng
authors.initials: L
authors.lastname: Wang
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Guan
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis*; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D011973:Receptors, LDL / Q000096:biosynthesis; D011989:Receptors, Thyrotropin / Q000378:metabolism; D013972:Thyrotropin; D015854:Up-Regulation
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D011973:Receptors, LDL; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D000242:Cyclic AMP; D006903:Hydroxymethylglutaryl CoA Reductases; D017868:Cyclic AMP-Dependent Protein Kinases