Neuroregulation of ProTRH biosynthesis and processing

This review presents an overview of the current knowledge on proTRH biosynthesis, its processing, its tissue distribution, and the role of known processing enzymes in proTRH maturation. The neuroendocrine regulation of TRH biosynthesis, the biological actions of its products, and the signal transduction and catabolic pathways used by those products are also reviewed. The widespread expression of proTRH, PC1, and PC2 rnRNAs in hypophysiotropic and extrahypophysiotropic areas of the brain, with their overlapping distribution in many areas, indicates the striking versatility provided by tissue-specific processing in generating quantitative and qualitative differences in nonTRH peptide products as well as TRH. Evidence is presented suggesting that differential processing for proTRH at the intracellular level is physiologically relevant. It is clear that control over the diverse range of proTRH-derived peptides within a specific cell is accomplished most from the regulation at the posttranslational level rather than the translational or transcriptional levels. Several examples supporting this hypothesis are presented in this review. A better understanding of proTRH-derived peptides role represents an exciting new frontier in proTRH research. These connecting sequences in between TRH molecules to form the precursor protein may function as structural or targeting elements that gu ide the folding and sorting of proTRH and its larger intermediates so that subsequent processing and secretion are properly regulated. The particular anatomical distribution of the proTRH end products, as well as regulation of their levels by neuroendocrine or pharmacological manipulations, supports a unique potential biologic role for these peptides.