Stimulation of CRH-mediated ACTH secretion by central administration of neurotensin: evidence for the participation of the paraventricular nucleus.

Abstract

Central administration of neurotensin (NT) stimulates hypothalamic-pituitary-adrenal (HPA) activity in freely-moving rats. Increases in adrenocorticotropin hormone (ACTH) and corticosterone (B) were observed 15 min following central NT administration and remained elevated for up to 4 h. Of the two NT fragments tested, NT1-8 and NT8-13, only NT8-13 was found to significantly elevate ACTH and B levels. Moreover, NT8-13 activated the HPA axis with a temporal profile similar to NT1-13, suggesting an interaction with the pharmacologically and molecularly characterized NT receptor. Animals pre-treated intravenously with the corticotropin-releasing hormone (CRH) antagonist, alpha-helical CRH, showed attenuated plasma ACTH and B responses to central NT administration. This indicates that CRH receptor activation is necessary for the stimulatory effects of NT on HPA function. Bilateral lesions of the paraventricular nucleus (PVN) of the hypothalamus significantly reduced NT-induced stimulation of ACTH and B release suggesting that the PVN is essential for NT's stimulatory action. Median eminence content studies indicated that acute central NT administration stimulates CRH, but not arginine vassopressin (AVP), release in animals examined 60 min following NT injection. Taken together, these findings suggest that the stimulatory effects of NT on HPA activity occur via specific NT receptors and that one site of action of NT is likely at the level of the PVN where NT elicits the release of CRH.