REGULATION OF CORTICOTROPIN-RELEASING FACTOR TYPE-1 (CRF1) RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN THE PARAVENTRICULAR NUCLEUS OF RAT HYPOTHALAMUS BY EXOGENOUS CRF

The present study sought to examine the effects of intracerebroventric ular (icv) administration of corticotropin-releasing factor (CRF) on t he expression of CRF, receptor messenger RNA (mRNA) within the hypotha lamus as determined by quantitative in situ hybridization histochemist ry. Adult male Sprague-Dawley rats were stereotaxically implanted with guide cannulae directed towards the right lateral ventricle. After 8- 10 days of recovery, either 10 mu l CRF (5 mu g) or vehicle solution w as injected into the lateral ventricle over a 2-min period. The rats w ere then deeply anesthetized at 15, 60, and 180 min after icv injectio n, transcardially perfused, and their brains cut into 30-mu m coronal sections. Brain sections were then processed using standard radioactiv e in situ hybridization histochemistry revealing the expression of the CRF, receptor mRNA. Low to moderate basal levels of CRF, receptor tra nscript were observed in several regions of the forebrain. However, th e hybridization signal for the mRNA encoding the CRF, receptor was bar ely detectable in the paraventricular nucleus of the hypothalamus (PVN ) of vehicle-injected rats. In contrast, 180 min after icv administrat ion of CRF, a significant increase in CRF, receptor transcript was mea sured specifically in the PVN, despite having virtually any hybridizat ion signal before 180 min. This increase in the level of receptor tran scription by CRF was restricted to the type 1 receptor subtype because the hybridization signal for the CRF(2 alpha) receptor mRNA was unaff ected in the brain regions in which it was located. Moreover, we confi rmed previous findings of a CRF-induced neuronal activation of parvoce llular neurosecretory cells of the PVN, as assessed by c-fos mRNA expr ession. This neuronal activation induced by exogenous CRF was also ass ociated with a rapid and strong induction of CRF heteronuclear RNA sel ectively in the rat PVN, a phenomenon abolished by a pretreatment with a CRF receptor antagonist. These results provide evidence that elevat ed levels of central CRF may trigger CRF, receptor transcription selec tively in the PVN. This positive feedback of CRF on its own receptor m ay represent a functional adaptation of the hypothalamic-pituitary-adr enal axis in response to stress.