DIFFERENTIAL COEXPRESSION OF GENES ENCODING PROTHYROTROPIN-RELEASING HORMONE (PRO-TRH) AND PROHORMONE CONVERTASES (PC1 AND PC2) IN RAT-BRAIN NEURONS - IMPLICATIONS FOR DIFFERENTIAL PROCESSING OF PRO-TRH

Pro-TRH is cleaved at paired basic residues to yield five copies of TR H and cryptic peptides. Recent studies have shown that the prohormone convertases, PC1 and PC2, can process pro-TRH correctly. To determine whether these two enzymes could play a role in pro-TRH processing in v ivo, the regional and cellular colocalization of pro-TRH messenger RNA (mRNA) with the mRNAs encoding the prohormone convertases PC1 and PC2 was examined in rat brain, using in situ hybridization histochemistry . Differential regional distribution of pro-TRH mRNA with PC1 and/or P C2 mRNA was found in several brain regions. For example, in the olfact ory regions, there was coexpression of pro-TRH mRNA in the glomerular layer with PC2 mRNA, but not PC1 mRNA, whereas in the tenia tecta, coe xpression of pro-TRH and PC1 mRNAs was evident, but PC2 mRNA was absen t. Pro-TRH mRNA in the paraventricular nucleus was coexpressed with bo th PC1 and PC2 mRNAs, whereas the basal lateral hypothalamus showed co existence of pro-TRH mRNA with PC2 mRNA, but not PC1 mRNA. Interesting ly, pro-TRH was expressed in the thalamic reticular nucleus, but neith er PC1 nor PC2 was detectable in this region. Cellular colocalization studies using double in situ hybridization histochemistry showed the p resence of PC2 mRNA in the pro-TRH neurons of the olfactory glomerular layer and basal lateral hypothalamus, and PC1 mRNA in the pro-TRH neu rons in the paraventricular nucleus. These results suggest that PC1 an d PC2 are enzyme candidates for the processing of pro-TRH in vivo. Mor eover, the differential distribution of PC1 and PC2 mRNAs with pro-TRH mRNA may be responsible for the differential processing of this proho rmone in the central nervous system. The absence of PC1 and PC2 mRNAs in certain TRH neurons raises the possibility that prohormone converta ses other than PC1 and PC2 may be involved in the processing of brain pro-TRH.