CORTICOTROPIN‐RELEASING HORMONE (CRH) MRNA EXPRESSION IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS (PVN) DURING EXPERIMENTAL COLITIS IN THE RAT

Abstract

Background Neuroendocrine–immune interactions can influence processes arising from the brain, and there is evidence that the central nervous system may amplify or modulate aspects of intestinal inflammation through alterations of the autonomic nervous system activity and/or stimulation of the hypothalamic–pituitary–adrenal (HPA) axis (American Journal of Physiology 276: G1027, 1999). But the effect of the colitis itself on the HPA axis remains unclear.Aim To investigate the effect of experimental colitis on the HPA‐axis, especially on CRH mRNA expression in the PVN, plasma adenocorticotropin (ACTH) and corticosterone (CORT) level.Methods Under isoflurane anesthesia, male SD rats (250–300 g) were induced to colitis by intracolonic administration of 0.2 mL of 50% ethanol (v/v) containing 20 mg of 2,4,6‐trinitrobenzenesulfonic acid (TNBS). In the first experiment, rats were sacrificed before and on days 1, 3, 7 and 14 after induction of colitis, and CRH mRNA levels in the PVN were quantified by in situ hybridization, plasma ACTH and CORT levels were measured by radioimmunoassay, and the colonic damage was assessed by measurement of colonic myeloperoxidase (MPO) activity. In the second experiment, rats were adrenalectomized bilaterally and corticosterone pellet was implanted subcutaneously (ADX + CORT). On day 3 after ADX + CORT, rats were infused TNBS (TNBS group) or saline (saline group) rectally and CRH mRNA level, plasma ACTH and CORT levels were measured on day 7 after administration of TNBS or saline. In the third experiment, pair‐fed rats whose daily food intake was matched to that of their pair in the colitic group were used, and on day 7 after treatment, CRH mRNA level, plasma ACTH and CORT levels were measured.Results In the first experiment, CRH mRNA levels in the PVN on days 3 and 7 after induction of colitis were significantly lower than those before induction of colitis (P < 0.05, P < 0.01, respectively). Plasma CORT levels during colitis were increased significantly (P < 0.001) from days 1 to 14, and plasma ACTH levels showed no significant change after day 3. In the second experiment, CRH mRNA level in the PVN in the TNBS group was significantly higher than those in the saline group (P < 0.01). In the third experiment, pair feeding resulted in no significant change in CRH mRNA, plasma ACTH and CORT levels.Conclusions These findings indicated that CRH mRNA expression in the PVN was inhibited by glucocorticoid feedback during this experimental colitis, and the decrease in food intake during colitis was not simply responsible for the expression of CRH mRNA.