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TSH Receptor Expression in Cardiac Muscle Tissue

Clinical Pharmacology and Therapeutics Unit Department of Medicine University of Melbourne Heidelberg, Victoria 3084, Australia

Address correspondence to: Albert G. Frauman, M.D., Department of Medicine, Austin and Repatriation Medical Centre, University of Melbourne, Studley Road, Heidelberg, Victoria 3084, Australia.

To the editor:

We thank Dr. Sellitti and colleagues for their comments concerning our study published in the May 2001 issue of JCEM (1, 2).

In our report (1), we were unable to detect the presence of mRNA transcripts in the muscle of any chamber of the normal human heart after a stringent RT-PCR approach with appropriate positive and negative controls. In light of these findings, which differed from the earlier report by Sellitti et al. (3), we performed corroborative experiments. Thus, in situ hybridization using specific non-overlapping oligonucleotide primers complementary to the human TSH receptor (TSHR) gene was negative on all chambers of the human heart in fresh frozen and paraffin- embedded sections. This negative result was further corroborated by Southern blot analysis of the RT-PCR experiments. The in situ hybridization and Southern blots were, appropriately, positive for the thyroid and consistent with PCR experiments, positive in extraocular muscle (4). As Sellitti et al. (3) point out in their original publication, the TSHR mRNA in porcine cardiac tissue showed the highest expression levels to be in the right atrium, coronary artery, and epicardial fat and the lowest levels in the ventricular myocardium; thus, it is possible that certain confounding positive tissues, rather than myocardial tissue itself, may have contributed to the positive results.

Although Dr. Sellitti and colleagues correctly point out that our results might also be interpreted as showing a very low, rather than absent, level of TSHR in cardiac muscle, it is nonetheless unlikely that negligible amounts of the receptor exist due to the consistent lack of detection by three sensitive methods, namely RT-PCR, Southern blot analysis, and in situ hybridization. Whereas these data suggest an absence of detectable transcripts of TSHR, we also agree with Dr. Sellitti and colleagues that a more extensive functional analysis of cardiac muscle activation of the TSHR, should it be present, would need to be conducted to definitively confirm that the TSHR may or may not be relevant to the cardiac manifestations of Graves’ disease.

Received March 21, 2002.

References

1. Busuttil BE, Frauman AG 2001 Extrathyroidal manifestations of Graves’ disease: the thyrotropin receptor is expressed in extraocular, but not cardiac, muscle tissues. J Clin Endocrinol Metab 86:2315–2319[Abstract/Free Full Text]
2. Sellitti DF, Doi SQ, Akamizu T, Koshiyama H 2002 Comment on thyrotropin receptor expression in cardiac muscle tissue. J Clin Endocrinol Metab 87:946[Free Full Text]
3. Sellitti DF, Hill R, Doi SQ, Akamizu T, Koshiyama H 1997 Differential expression of thyrotropin receptor mRNA in the porcine heart. Thyroid 7:641–646[Medline]
4. Major BJ, Cures A, Frauman AG 1997 The full-length and splice variant thyrotropin receptor is expressed exclusively in skeletal muscle of extraocular origin: a link in the pathogenesis of Graves’ ophthalmopathy. Biochem Biophys Res Commun 230:493–496[CrossRef][Medline]

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