NEUROPEPTIDE-Y (NPY) ACTIONS ON THE CORTICOTROPH CELL OF THE ANTERIOR-PITUITARY GLAND ARE NOT MEDIATED BY A DIRECT EFFECT

Neuropeptide Y has been implicated in the activation of the hypothalam ic-pituitary-adrenal (HPA) axis, the regulation of growth and sexual f unction, and is the most potent stimulant of feeding yet reported. The actions of NPY on the HPA axis are thought to be mediated via an acti vation of the corticotrophin releasing hormone (CRH) neurones within t he paraventricular nucleus of the hypothalamus. The ability of NPY to directly influence the corticotroph cell is currently controversial. T hese studies investigated whether NPY could have a direct influence on anterior pituitary adrenocorticotrophic hormone (ACTH) release. In di spersed male rat anterior pituitary cells, NPY (1-1000 nM) had no effe ct on either basal or CRH (1 nM) stimulated ACTH release. Basal releas e, NPY (1000 nM) 111+/-6% vs. control 103+/-5%. CRH stimulated release , CRH (1 nM) with NPY (1000 nM) 226+/-23% vs. CRH (1 nM) alone 228+/-2 0%. In addition, NPY (1000 nM) had no effect on either basal or CRH (1 nM) stimulated ACTH release in the mouse corticotroph cell line, AtT- 20. Thus, in two models of the anterior pituitary corticotroph NPY had no effect on ACTH release. NPY induced activation of the HPA axis is likely to be mediated via a modulation of hypothalamic CRH and not via a direct action at the level of the anterior pituitary. (C) 1998 Else vier Science B.V. All rights reserved.