Role of corticotropin-releasing hormone in gastrin-releasing peptide-mediated regulation of corticotropin and corticosterone secretion in male rats.
Gastrin-releasing peptide (GRP) exerts several functions within the hypothalamus and may be involved in the regulation of pituitary hormone secretion. The purpose of this study was to investigate the central effect of GRP on hypothalamic-pituitary-adrenal axis activity in the male rat. Intracerebroventricular (i.c.v.) but not intravenous administration of GRP (1, 10, 100 ng/rat) increased plasma ACTH and corticosterone concentrations in a dose-dependent manner. The highest dose (100 ng/rat) of GRP increased plasma ACTH and corticosterone 4- and 14-fold, respectively. This increase peaked at 30-60 min after i.c.v. injection, decreased gradually and returned to baseline levels 240 min after GRP administration. The i. c.v. administration of (Leu13-psi-CH2NH-Leu14) bombesin, a competitive and specific GRP receptor antagonist, had no effect on ACTH and corticosterone secretion; however, a dose of 1 microg/rat completely blocked the increase of both hormones induced by GRP (10 ng). By using alpha-helical (9-41) corticotropin-releasing factor (CRF), a competitive antagonist of CRF, the role of CRF on GRP-induced ACTH and corticosterone secretion was also explored. alpha-Helical (9-41) CRF (10 microg/rat) blocked the increase in ACTH and corticosterone secretion induced by GRP (10 ng). The results obtained in this study suggest that GRP increases the secretion of ACTH and corticosterone in the plasma by acting centrally on GRP receptors, and that endogenous GRP receptor ligands do not tonically regulate ACTH and corticosterone secretion. Furthermore, the hypothalamus-pituitary-adrenal-activating effects induced by GRP appear to be mediated, at least in part, by CRF.
Departamento de Farmacología, Facultad de Farmacia and Instituto Pluridisciplinar, Universidad Complutense de Madrid, Madrid, España.
M M
MM
Garrido
S
S
Martin
E
E
Ambrosio
J A
JA
Fuentes
J
J
Manzanares
D000302:Adrenal Cortex / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D003345:Corticosterone / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019886:Gastrin-Releasing Peptide / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D019886:Gastrin-Releasing Peptide; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D001839:Bombesin; D003345:Corticosterone