Hypothalamus, anterior pituitary and adrenal gland involvement in the activation of adrenocorticotropin and corticosterone secretion by gastrin-releasing peptide.

This study was designed to investigate the contribution of the hypothalamus, anterior pituitary and adrenal gland in the increase of adrenocorticotropin (ACTH) and corticosterone secretion induced by gastrin-releasing peptide (GRP) on in vitro isolated hypothalamus, pituitary and adrenal gland. Furthermore, we have examined in dispersed anterior pituitary cells whether the ACTH release induced by GRP is a Ca2+-dependent process. Moderate concentrations of GRP (1 and 10 nM) were able to increase the release of corticotropin-releasing factor (CRF)-like material in the medium of isolated hypothalami, whereas higher concentrations (100 and 1000 nM) were needed to elevate ACTH and corticosterone secretion in pituitary and adrenal quarters, respectively. The competitive and specific GRP receptor antagonist (Leu13-psi-CH2NH-Leu14) bombesin (10, 100 and 1000 nM) was without effect on basal secretion of CRF-like material, ACTH and corticosterone in isolated hypothalami, pituitary and adrenal quarters respectively. However, this antagonist (100 nM) completely blocked the stimulatory effects of GRP (100 nM) on bioactive CRF, ACTH and corticosterone release. In addition, in dispersed anterior pituitary cells which medium contained Ca2+ (1.5 mM), GRP stimulated the secretion of ACTH, but was without effect when the concentration of Ca2+ in the medium was lower (200 nM). These results suggest that: (1) the hypothalamus, anterior pituitary and adrenal gland seem to contribute to the elevation of ACTH and corticosterone secretion induced by GRP by a mechanism mediated through GRP receptors and (2) the stimulation of ACTH by GRP in the anterior pituitary appears to be dependent upon the presence of physiological concentrations of extracellular Ca2+. Copyright 1999 Elsevier Science B.V.