Prepro-thyrotropin releasing hormone 178-199 immunoreactivity is altered in the hypothalamus of the Wistar-Kyoto strain of rat.

The rat prepro-thyrotropin releasing hormone (TRH) 178-199 is derived from prepro-TRH by the actions of the endopeptidases, prohormone convertase 1 (PC1) and PC2. PPTRH 178-199 attenuates the synthesis and secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary both in vitro and in vivo, suggesting an inhibitory action on hypothalamic-pituitary-adrenal (HPA) axis function. This peptide also acts centrally to increase activity and decrease anxiety related behaviors. To elucidate the involvement of this peptide in these functions, we have compared the expression of PPTRH 178-199, PPTRH mRNA, and PC1 and PC2 mRNAs in the Wistar-Kyoto (WKY) and Wistar strains of rat. WKY rats have been shown to possess neuroendocrine abnormalities (HPA hyper-activity) and hyper-emotional behavioral characteristics. Immunohistochemical analysis of PPTRH 178-199 demonstrated significant strain differences in the paraventricular nucleus (PVN) of the hypothalamus and the parastrial nucleus (PSN). WKY rats had significantly greater numbers of immunoreactive (IR) cell body profiles (P<0.0005) than Wistar rats in the PVN and a significantly lower fiber density (P<0.002) in the PSN. Levels of PPTRH, PC1, and PC2 mRNA were not different between strains in any brain region examined. These data suggest that altered levels of PPTRH 178-199 in WKY rats could cause, at least in part, the hyper-activity of the HPA axis and the hyper-emotional behavioral characteristics seen in this rat strain. Such data fit with the hypothesis that PPTRH 178-199 is involved in the regulation of the HPA axis and behavior.