The influence of sex and gonadectomy on the growth hormone and corticosterone response to hexarelin in the rat

The present study is designed to investigate the role of sex and gonadal st atus in the growth hormone (GH) and corticosterone response to hexarelin (H EXA), a GH-releasing peptide, which also causes a stimulatory action on the hypothalamic-pituitary-adrenal (HPA) axis. HEXA (80 mug/Kg) was administer ed intracarotid to anesthetized intact or gonadectomized male (ORC) and fem ale (OVX) middle-aged rats. The GH stimulatory response to HEXA was gender- related since the GH increase was significantly (p< 0.001) higher in intact males (area under the curve, AUC= 12560 +/- 1784 ng/ml.45 min) than in fem ales (AUC= 4628 +/- 257 ng/ml.45 min). This sex difference does not depend on circulating gonadal steroids since it persists in ORC (AUC = 11980 +/- 1 136 ng/ml.45 min) and OVX (AUC = 5539 +/- 614 ng/ml.45 min) rats. The diffe rent effects of HEXA on corticosterone secretion detected in male and femal e rats are probably dependent on the prevailing activity of the HPA axis. I n fact, in male rats that have low basal corticosterone levels, HEXA caused an increase in corticosterone secretion, which was significantly (p<.05) h igher in ORC than in intact rats. The increase in corticosterone secretion by HEXA both in intact and OVX females was delayed, probably due to the ele vated initial corticosterone levels, which could have activated the glucoco rticoid negative feedback. We suggest that gender-specific patterns in the regulation of the hypothalamus-pituitary function could be responsible for the GH and corticosterone sexually differentiated responses to HEXA. (C) 20 00 Elsevier Science Inc. All rights reserved.