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

Authors

  • Limin Tian,

    1. Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China
    2. Institute of Endocrinology, Shandong Academy of Clinical Medicine; Jinan, China,
    Current affiliation:
    1. Department of Endocrinology, People's Hospital of Gansu Province
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    • *

      These authors contributed equally to this study.

  • Yongfeng Song,

    1. Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China
    2. Institute of Endocrinology, Shandong Academy of Clinical Medicine; Jinan, China,
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    • *

      These authors contributed equally to this study.

  • Mingzhao Xing,

    1. Division of Endocrinology, the Johns Hopkins University School of Medicine, Baltimore, MD
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    • *

      These authors contributed equally to this study.

  • Wei Zhang,

    1. Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China
    Current affiliation:
    1. Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Jinan, China
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    • *

      These authors contributed equally to this study.

  • Guang Ning,

    1. Shanghai Institute of Endocrinology, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Xiaoying Li,

    1. Shanghai Institute of Endocrinology, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Chunxiao Yu,

    1. Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China
    2. Institute of Endocrinology, Shandong Academy of Clinical Medicine; Jinan, China,
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  • Chengkong Qin,

    1. General Surgery, Provincial Hospital affiliated to Shandong University, Jinan, China
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  • Jun Liu,

    1. Organ Transplantation Surgery, Provincial Hospital affiliated to Shandong University, Jinan, China
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  • Xingsong Tian,

    1. General Surgery, Provincial Hospital affiliated to Shandong University, Jinan, China
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  • Xianglan Sun,

    1. Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China
    2. Institute of Endocrinology, Shandong Academy of Clinical Medicine; Jinan, China,
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  • Rui Fu,

    1. Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China
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  • Lin Zhang,

    1. Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China
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  • Xiujuan Zhang,

    1. Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China
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  • Yan Lu,

    1. Shanghai Institute of Endocrinology, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Jianwen Zou,

    1. Clinical Laboratory, and Provincial Hospital affiliated to Shandong University, Jinan, China
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  • Laicheng Wang,

    1. Scientific Center, Provincial Hospital affiliated to Shandong University, Jinan, China,
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  • Qingbo Guan,

    1. Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China
    2. Institute of Endocrinology, Shandong Academy of Clinical Medicine; Jinan, China,
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  • Ling Gao,

    Corresponding author
    1. Scientific Center, Provincial Hospital affiliated to Shandong University, Jinan, China,
    2. Institute of Endocrinology, Shandong Academy of Clinical Medicine; Jinan, China,
    • Provincial Hospital affiliated to Shandong University, 324 Jing 5 Road, Jinan, Shandong Province, 250021 China
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    • fax: +86 531 87939639

  • Jiajun Zhao

    Corresponding author
    1. Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China
    2. Institute of Endocrinology, Shandong Academy of Clinical Medicine; Jinan, China,
    • Department of Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China
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    • fax: +86 531 87939639


  • Potential conflict of interest: Nothing to report.

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. (HEPATOLOGY 2010)

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