Colitis induces CRF expression in hypothalamic magnocellular neurons and blunts CRF gene response to stress in rats

We investigated hypothalamic neuronal corticotropin-releasing factor (CRF) gene expression changes in response to visceral inflammation induced by 2,4 ,6-trinitrobenzenesulfonic acid (TNB) and acute stress. Seven days after TN B, rats were subjected to water-avoidance stress (WAS) or restraint for 30 min and euthanized. Hypothalamic CRF primary transcripts (heteronuclear RNA , hnRNA) and CRF and arginine vasopressin (AVP) mRNAs were assessed by in s itu hybridization. Antisense S-35-labeled cRNA probes against CRF mRNA intr onic and exonic sequences and an oligonucleotide probe against the AVP mRNA were used. TNB induced macroscopic lesions and a fivefold elevation in mye loperoxidase activity in the colon. Colitis increased CRF hnRNA and mRNA si gnals in the magnocellular part of the paraventricular nucleus of the hypot halamus (PVN) and supraoptic neurons, whereas AVP mRNA was not altered. Col itis did not modify CRF hnRNA signal in the parvocellular part of the PVN ( pPVN), plasma corticosterone, and serum osmolarity levels. However, CRF hnR NA expression in the pPVN and the rise in corticosterone and defecation ind uced by WAS or restraint were blunted in colitic rats. These data show that colitis upregulates CRF gene synthesis in magnocellular hypothalamic neuro ns but dampens CRF gene transcription in the pPVN and plasma corticosterone responses to environmental acute stressors.