Frog prohormone convertase PC2 mRNA has a mammalian‐like expression pattern in the central nervous system and is colocalized with a subset of thyrotropin‐releasing hormone‐expressing neurons

Abstract

The prohormone convertase (PC2) is expressed in the mammalian central nervous system (CNS) and has been shown to play an important role in the processing of certain neuropeptide precursors and prohormones at paired basic residues. Amphibian PC2 cDNA was recently cloned for the frog Xenopus laevis, and both its sequence and its pituitary expression pattern were shown to be very similar to those of mammalian PC2. To investigate further the function of PC2 in the vertebrate CNS, we used in situ hybridization histochemistry to localize the distribution of cells expressing PC2 mRNA in the frog brain and the spinal cord. The distribution of PC2-expressing cells was also compared with that of cells expressing thyrotropin-releasing hormone (TRH) mRNA or peptide. PC2-expressing cells were detected in specific nuclei that were widely distributed in the frog CNS. In forebrain, telencephalic PC2 mRNA was found in the olfactory bulb, pallium, striatum, amygdala, and septum, and diencephalic PC2 mRNA was seen in the preoptic area, thalamus, and hypothalamus. More posteriorly, PC2 cells were localized to midbrain tegmentum, 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 brain nuclei. Regions with higher levels showed good correspondence to areas shown by others in frog to contain large numbers of neuropeptide-expressing cells, including TRH cells. On the other hand, not all brain areas with high levels of TRH mRNA had high levels of PC2 mRNA. Localization studies combining in situ hybridization and immunocytochemistry showed that, at least in optic tectum and brainstem, PC2 mRNA and pro-TRH peptide coexist. These findings suggest that pro-TRH is processed by PC2 in some, but possibly not all, brain regions. Thus, different converting enzymes may be involved in pro-TRH processing in different brain regions.