Expression of Multiple Corticotropin-Releasing Hormone Receptors in the Human Heart

Edward W. Hillhouse and Emmanouil Karteris

Department of Biological Sciences, Medical Research Institute, University of Warwick Coventry CV4 7AL, United Kingdom

Address correspondence to: Prof. E. W. Hillhouse, Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom. E-mail: . ehillhouse{at}bio.warwick.ac.uk

To the editor:

We read with great interest the recent paper by Kimura and colleagues (1). The authors report the expression of multiple CRH-receptor subtypes and urocortin in the human heart. These findings may have important implications for cardiovascular function in humans. We have some concerns, however, about the validity and interpretation of the CRH-receptor expression data. They state that the expression of CRH-R1 and CRH-R2ß receptor subtypes in some biopsies was weaker when compared with the expression of the CRH-R2{alpha} subtype. However, the technique they used is not quantitative, and the difference in the intensity of the PCR products could be due to the fact that different sequences amplify at different rates. Unless the authors demonstrate that all of their primers amplify all CRH receptors with the same efficiency at the linear range of the amplification reaction, conclusions cannot be drawn regarding the predominance of a receptor subtype.

Although the authors have designed specific primers for CRH-R2 subtypes, this was not the case for the CRH-R1. The primers used in this study can amplify both 1{alpha} and 1ß subtypes. The lack of expression of 1ß might be due to preferential amplification of the 1{alpha} subtype. We have identified, by PCR and sequencing, both these subtypes differentially expressed in human cardiac compartments (our unpublished data). Moreover, the authors do not take into consideration recent literature regarding CRH-R1 variants (2, 3). It could be possible that what they interpret as nonspecific bands may be alternative CRH-R1 splice variants. For this reason, sequencing of any PCR products is vital. The presence of multiple CRH-R1 receptors is of considerable importance because they have different ligand binding and signaling properties (3). We have also identified by PCR and sequencing analysis CRH-R2{alpha} transcripts in different compartments of the heart, but not CRH-R2ß.

More studies should be undertaken to dissect in more detail the CRH receptor repertoire in human cardiac tissues and to further investigate the functionality of these receptors.

Received January 31, 2002.

References

  1. Kimura Y, Takahashi K, Totsune K, Muramatsu Y, Kaneko C, Darnel AD, Suzuki T, Ebina M, Nukiwa T, Sasano H 2002 Expression of Urocortin and Corticotropin-Releasing Factor Receptor Subtypes in the Human Heart. J Clin Endocrinol Metab 87:340–346[Abstract/Free Full Text]
  2. Pisarchik A, Slominski AT 2001 Alternative splicing of CRH-R1 receptors in human and mouse skin: identification of new variants and their differential expression. FASEB 15:2754–2756[Abstract/Free Full Text]
  3. Grammatopoulos D, Dai Y, Randeva HS, Levine MA, Karteris E, Easton A, Hillhouse EW 1999 A novel splice variant of the type-1 corticotropin-releasing hormone (CRH) receptor with a deletion in the 7th transmembrane domain present in the human pregnant term myometrium and fetal membranes. Mol Endocrinol 13:2189–2102[Abstract/Free Full Text]




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