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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†

  1. Limin Tian1,6,‡,¶,
  2. Yongfeng Song1,6,¶,
  3. Mingzhao Xing7,¶,
  4. Wei Zhang1,§,¶,
  5. Guang Ning8,
  6. Xiaoying Li8,
  7. Chunxiao Yu1,6,
  8. Chengkong Qin2,
  9. Jun Liu3,
  10. Xingsong Tian2,
  11. Xianglan Sun1,6,
  12. Rui Fu1,
  13. Lin Zhang1,
  14. Xiujuan Zhang1,
  15. Yan Lu8,
  16. Jianwen Zou4,
  17. Laicheng Wang5,
  18. Qingbo Guan1,6,
  19. Ling Gao5,6,‖,*,
  20. Jiajun Zhao1,6,††,*

Article first published online: 11 JUN 2010

DOI: 10.1002/hep.23800

Issue

Hepatology

Hepatology

Volume 52, Issue 4, pages 1401–1409, October 2010

Additional Information

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

Author Information

  1. 1

    Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China

  2. 2

    General Surgery, Provincial Hospital affiliated to Shandong University, Jinan, China

  3. 3

    Organ Transplantation Surgery, Provincial Hospital affiliated to Shandong University, Jinan, China

  4. 4

    Clinical Laboratory, and Provincial Hospital affiliated to Shandong University, Jinan, China

  5. 5

    Scientific Center, Provincial Hospital affiliated to Shandong University, Jinan, China,

  6. 6

    Institute of Endocrinology, Shandong Academy of Clinical Medicine; Jinan, China,

  7. 7

    Division of Endocrinology, the Johns Hopkins University School of Medicine, Baltimore, MD

  8. 8

    Shanghai Institute of Endocrinology, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

  1. ‡

    Department of Endocrinology, People's Hospital of Gansu Province

  2. §

    Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Jinan, China

  1. These authors contributed equally to this study.

  2. ‖

    fax: +86 531 87939639

  3. ††

    fax: +86 531 87939639

*Provincial Hospital affiliated to Shandong University, 324 Jing 5 Road, Jinan, Shandong Province, 250021 China

  • †

    Potential conflict of interest: Nothing to report.

  • These authors contributed equally to this study.

  • ‖

    fax: +86 531 87939639

  • ††

    fax: +86 531 87939639

Publication History

  1. Issue published online: 11 JUN 2010
  2. Article first published online: 11 JUN 2010
  3. Manuscript Accepted: 2 JUN 2010
  4. Manuscript Received: 25 MAR 2010

Funded by

  • Supported by the Natural Science Foundation of China (30971409) and the Natural Science Foundation of Shandong Province ZR2009CZ009

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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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