Pro-GnRH processing

Abstract

An inspection of the deduced amino acid sequences from the nine complementary pro-GnRH forms demonstrates several points. All pro-gonadotropin-releasing hormone (GnRH) proteins contain GnRH at their N-termini and the peptide is separated by a putative processing site from GnRH-associated peptide (GAP). The organization and spatial arrangement of these sequences suggest that the enzymes that process the pro-GnRH in a given cell are similar across all species. In addition, excision of the GnRH peptide from the precursor is performed by an endopeptidase. Because most peptide precursors appear to be processed at monobasic or dibasic residues, the endopeptidase could cleave the pro-GnRH after the Lys or Arg residues. The regulation of peptide bioactivity is a complex process. Cells have devised ingenious mechanisms to control the amounts of peptides available for release. Some of these processes include gene transcription, pre-RNA splicing, protein biosynthesis, trafficking of the precursor to the regulated secretory pathway, conversion of the pro-peptide to fully processed product, secretion, and degradation. There is considerable controversy regarding the regulation of GnRH transcription in vivo , and in many cases, control appears to occur posttranscriptionally.