Structure of the gene encoding rat thyrotropin releasing hormone.

The gene encoding the hypothalamic peptide thyrotropin releasing hormone (TRH) was isolated from two rat genomic bacteriophage libraries. Southern blot analysis indicates that the gene is present as a single copy in the rat genome. The transcriptional unit is 2.6 kilobases in size and contains three exons interrupted by two introns of approximately 750 and 450 base pairs. Exon 1 encodes the 5'-untranslated region of the mRNA, exon 2 encodes the signal sequence and the majority of the amino-terminal peptide, and exon 3 encodes the remainder of the amino-terminal peptide, five copies of the TRH sequence, the carboxyl-terminal peptide, and the 3'-untranslated region of the mRNA. The general structure of the TRH gene resembles that of three other polypeptide hormone genes, preproopiomelanocortin, preproenkephalin A, and preproenkephalin B. Further sequence analysis revealed that characteristic promoter elements are present in the 5'-flanking region of the TRH gene. In addition, sequence homologies with the glucocorticoid receptor binding site, the GC box hexanucleotide, and a portion of the flanking region of the thyroid stimulating hormone beta-subunit gene were also identified. These upstream sequences may be important for the regulation of TRH gene expression.