Immune challenge-stimulated hypophysiotropic corticotropin-releasing hormone messenger RNA expression is associated with an induction of neurotensin messenger RNAs without alteration of vasopressin messenger RNAs

The corticotropin-releasing hormone neurons of the hypothalamic paraventric ular nucleus are the final common pathway of the neuroendocrine adaptative response to a variety of stressors. To meet varied homeostatic needs, corti cotropin-releasing hormone neurons exhibit a marked phenotypical plasticity , enabling them to rapidly modify their neuroendocrine output. In particula r, they synthesize the neuropeptides vasopressin and neurotensin. Under man y experimental circumstances, it is observed that corticotropin-releasing h ormone and vasopressin are regulated in parallel, whereas the expression of neurotensin seems dissociated, in these neurons, evoking different transcr iptional control over the co-existing neuropeptides depending on the adapta tive response required. Using radioactive and dual-label in situ hybridizat ion techniques, we have studied the respective expression of paraventricula r corticotropin-releasing hormone, vasopressin and neurotensin messenger RN As in the context of an immune challenge. A single intraperitoneal injectio n of the endotoxin lipopolysaccharide was administered to adult male rats t hat were killed 8 h later. Compared to control animals, lipopolysaccharide- injected rats showed elevated plasma corticosterone (614+/-65 vs 185+/-40 n g/ml in control) and increased expression of paraventricular corticotropin- releasing hormone messenger RNA (+200%); expression of neurotensin messenge r RNA was induced in about one-third of corticotropin-releasing hormone neu rons, whereas vasopressin messenger RNA expression remained unchanged. Therefore, in this experimental context and at the time-point examined, co- existing corticotropin-releasing hormone and vasopressin appeared different ially expressed, and an additional stimulus (inflammation) is demonstrated to result in neurotensin expression in neuroendocrine corticotropin-releasi ng hormone neurons. Neurotensin may be released in the pituitary portal blo od to trigger pituitary response associated with mobilization of the immune system. (C) 1999 IBRO. Published by Elsevier Science Ltd.