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 TNB, 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 situ hybridization. Antisense (35)S-labeled cRNA probes against CRF mRNA intronic and exonic sequences and an oligonucleotide probe against the AVP mRNA were used. TNB induced macroscopic lesions and a fivefold elevation in myeloperoxidase activity in the colon. Colitis increased CRF hnRNA and mRNA signals in the magnocellular part of the paraventricular nucleus of the hypothalamus (PVN) and supraoptic neurons, whereas AVP mRNA was not altered. Colitis did not modify CRF hnRNA signal in the parvocellular part of the PVN (pPVN), plasma corticosterone, and serum osmolarity levels. However, CRF hnRNA expression in the pPVN and the rise in corticosterone and defecation induced by WAS or restraint were blunted in colitic rats. These data show that colitis upregulates CRF gene synthesis in magnocellular hypothalamic neurons but dampens CRF gene transcription in the pPVN and plasma corticosterone responses to environmental acute stressors.
Kresse
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CURE: Digestive Diseases Research Center, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA.
Million
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M
Saperas
E
E
Taché
Y
Y
D000818:Animals; D001769:Blood / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects; D015870:Gene Expression; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009994:Osmolar Concentration; D012332:RNA, Heterogeneous Nuclear / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000235:genetics*; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
D012332:RNA, Heterogeneous Nuclear; D012333:RNA, Messenger; D014302:Trinitrobenzenesulfonic Acid; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone