Two isoforms of the thyrotropin-releasing hormone receptor generated by alternative splicing have indistinguishable functional properties.

Two cDNA clones encoding two different isoforms of the thyrotropin-releasing hormone receptor (TRH-R) from GH3 rat anterior pituitary cells have been isolated. One isoform corresponds to the TRH-R(412) receptor previously described (de la Peña, P., Delgado, L. M., del Camino, D., and Barros, F. (1992) Biochem. J. 284, 891-899). The second one, named TRH-R(387), contains a 52-base pair deletion, which yields a new variant of the receptor protein 25 amino acid shorter and which contains 12 new residues on its carboxyl terminus. This new isoform is produced by alternative splicing of a retained intron in the primary transcript of a gene represented only once in the rat genome. Furthermore, the perfect colinearity between genomic DNA and TRH-R(412) cDNA demonstrates that no other introns are present within the coding region of the TRH receptor gene. Functional expression in Xenopus laevis oocytes indicates that both cDNAs encode fully functional TRH receptors. Otherwise, indistinguishable electrophysiological responses to TRH are evoked in oocytes expressing both receptor isoforms.