Identification and characterization of thyrotropin-releasing hormone precursor peptides in rat brain.

The sequence of rat hypothalamic pro-TRH, deduced by sequencing of cDNA, contains five copies of the TRH progenitor sequence Gln-His-Pro-Gly flanked by paired basic amino acid sequences. The TRH prohormone also contains leader and trailer sequences and four intervening sequences. We have developed two RIAs against synthetic peptides corresponding to sequences within the deduced pro-TRH sequence and have used these assays to identify and partially characterize four pro-TRH-derived peptides distinct from TRH in extracts of rat brain tissue. Two of these peptides contain incompletely processed TRH sequences; the other two peptides are probably derived from the N-terminal leader sequence. The presence of these authentic pro-TRH-derived peptides indicates that pro-TRH may give rise to a family of peptides other than TRH, some of which may be of biological significance.