FROG PROHORMONE CONVERTASE PC2 MESSENGER-RNA HAS A MAMMALIAN-LIKE EXPRESSION PATTERN IN THE CENTRAL-NERVOUS-SYSTEM AND IS COLOCALIZED WITH A SUBSET OF THYROTROPIN-RELEASING HORMONE-EXPRESSING NEURONS

The prohormone convertase (PC2) is expressed in the mammalian central nervous system (CNS) and has been shown to play an important role in t he processing of certain neuropeptide precursors and prohormones at pa ired basic residues. Amphibian PC2 cDNA was recently cloned for the fr og Xenopus laevis, and both its sequence and its pituitary expression pattern were shown to be very similar to those of mammalian PC2. To in vestigate further the function of PC2 in the vertebrate CNS, we used i n situ hybridization histochemistry to localize the distribution of ce lls expressing PC2 mRNA in the frog brain and the spinal cord. The dis tribution of PC2-expressing cells was also compared with that of cells expressing thyrotropin-releasing hormone (TRH) mRNA or peptide. PC2-e xpressing cells were detected in specific nuclei that were widely dist ributed in the frog CNS. In forebrain, telencephalic PC2 mRNA was foun d in the olfactory bulb, pallium, striatum, amygdala, and septum, and diencephalic PC2 mRNA was seen in the preoptic area, thalamus, and hyp othalamus. More posteriorly, PC2 cells were localized to midbrain tegm entum, the torus semicircularis, and the optic tectum, as well as the cerebellum, brainstem, and spinal cord. Despite this wide distribution , steady-state levels of PC2 mRNA were clearly different in various br ain nuclei. Regions with higher levels showed good correspondence to a reas shown by others in frog to contain large numbers of neuropeptide expressing cells, including TRH cells. On the other hand, not all brai n areas with high levels of TRH mRNA had high levels of PC2 mRNA. Loca lization studies combining in situ hybridization and immunocytochemist ry showed that, at least in optic tectum and brainstem, PC2 mRNA and p ro-TRH peptide coexist. These findings suggest that pro-TRH is process ed by PC2 in some, but possibly not all, brain regions. Thus, differen t converting enzymes may be involved in pro-TRH processing in differen t brain regions. (C) 1995 Wiley-Liss, Inc.