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 I (P CI) and PC2. PPTRH 178-199 attenuates the synthesis and secretion of adreno corticotropic 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 thi s peptide in these functions, we have compared the expression of PPTRH 178- 199, PPTRH mRNA, and PCI and PC2 mRNAs in the Wistar-Kyoto (WKY) and Wistar strains of rat. WKY rats have been shown to possess neuroendocrine abnorma lities (HPA hyper-activity) and hyper-emotional behavioral characteristics. Immunohistochemical analysis of PPTRH 178-199 demonstrated significant str ain differences in the paraventricular nucleus (PVN) of the hypothalamus an d the parastrial nucleus (PSN). WKY rats had significantly greater numbers of immunoreactive OR) cell body profiles (P <0.0005) than Wistar rats in th e PVN and a significantly lower fiber density (P <0.002) in the PSN. Levels of PPTRH, PCI, and PC2 mRNA were not different between strains in any brai n 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 ax is and the hyper-emotional behavioral characteristics seen in this rat stra in. Such data fit,vith the hypothesis that PPTRH 178-199 is involved in the regulation of the HPA axis and behavior. (C) 2001 Elsevier Science B.V. Al l rights reserved.