We measured amounts of thyrotropin-releasing hormone receptor (TRHR) mRNA in human pituitary tumors, and found a novel transcript of the TRHR gene. Competitive PCR revealed expression of the TRHR mRNA in all pituitary adenomas examined, and its level was variable and similar to that in the normal pituitary. When the C-terminal region was amplified by PCR, an additional short product was observed. Cloning and sequence analysis of this short fragment revealed that the deleted sequence corresponded exactly to the 5' sequence of exon 3, indicating alternative splicing of the TRHR mRNA. This alternative splicing resulted in a frame shift yielding a C-terminal truncated protein (HTRHR2) on translation. The mRNA ratio of the HTRHR2 versus the wild-type was significantly different among pituitary tumors.