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Functional thyrotropin receptor expression in the ventricle and the effects on ventricular BNP secretion

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Abstract

Elevated thyrotropin (TSH) and hypercholesterolemia commonly coexist in patients with subclinical hypothyroidism, which can cause and aggravate heart disease. However, it is unclear whether TSH has a direct effect on cardiac function. To determine the expression of the thyrotropin receptor (TSHR) and the effects of TSH on ventricular function, we analyzed the ventricular tissues and thyroid glands from normal rats and mice and the H9c2 cardiomyocyte cell line. The results revealed that TSHR was expressed at the transcriptional and protein levels by PCR, immunoblotting, immunohistochemistry and immunofluorescence. The mRNA levels of β-MHC and the expression of pCREB and HMGCR in the ventricle were significantly lower in Tshr −/− mice than in wild-type (WT) mice (p < 0.05), but serum NT-proBNP levels were similar between WT and Tshr −/− mice. After synchronization, H9c2 cells were stimulated with several concentrations of TSH for various time periods. TSH up-regulated β-MHC mRNA expression in H9c2 cells. Cyclic adenosine monophosphate (cAMP) production and downstream signaling, such as pCREB and HMGCR expression and NT-proBNP secretion, increased in dose- and time-dependent manners. The TSH-stimulated effects were suppressed by an adenylyl cyclase inhibitor, a protein kinase A (PKA) inhibitor and HMGCR inhibitors (all p < 0.05). The data indicate functional TSHR is expressed in ventricular myocytes and mediates TSH-induced BNP secretion and HMGCR up-regulation through the cAMP/PKA/pCREB signaling pathway. Our findings suggest a potentially novel pathophysiological role of TSH in heart failure-associated hypothyroidism.

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Acknowledgments

This work was supported by Grants from National Basic Research Program of China (2012CB524900), the National Natural Science Foundation of China (30971409, 30901461, 81230018, 81170794 and 81270869) and Natural Science Foundation (ZR2009CZ009) and the international cooperation Grant (2011) of Shandong Province of China and Jinan self-renovation plan of colleges and universities as well as scientific research institutes (2012).

Conflict of interest

The authors declare that there is no conflict of interests.

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Authors and Affiliations

  1. Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jing 5 Road, Jinan, Shandong, 250021, China

    Wen Huang, Jin Xu, Fei Jing & Jia-Jun Zhao

  2. Shandong Clinical Medical Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, 250021, China

    Wen Huang, Jin Xu & Fei Jing

  3. Department of Healthcare, Qianfoushan Hospital Affiliated to Shandong University, Jinan, 250014, China

    Wen Huang

  4. Department of Scientific Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China

    Wen-Bin Chen & Ling Gao

  5. Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jing 5 Road, Jinan, Shandong, 250021, China

    Hai-Tao Yuan

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  1. Wen Huang
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Correspondence to Hai-Tao Yuan or Jia-Jun Zhao.

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Huang, W., Xu, J., Jing, F. et al. Functional thyrotropin receptor expression in the ventricle and the effects on ventricular BNP secretion. Endocrine 46, 328–339 (2014). https://doi.org/10.1007/s12020-013-0052-6

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