CENTRAL EFFECTS OF GROWTH HORMONE-RELEASING HEXAPEPTIDE (GHRP-6) ON GROWTH-HORMONE RELEASE ARE INHIBITED BY CENTRAL SOMATOSTATIN ACTION

Citation
Km. Fairhall et al., CENTRAL EFFECTS OF GROWTH HORMONE-RELEASING HEXAPEPTIDE (GHRP-6) ON GROWTH-HORMONE RELEASE ARE INHIBITED BY CENTRAL SOMATOSTATIN ACTION, Journal of Endocrinology, 144(3), 1995, pp. 555-560
Citations number
32
Categorie Soggetti
Endocrynology & Metabolism
Journal title
ISSN journal
00220795
Volume
144
Issue
3
Year of publication
1995
Pages
555 - 560
Database
ISI
SICI code
0022-0795(1995)144:3<555:CEOGHH>2.0.ZU;2-R
Abstract
Growth hormone (GH) release is stimulated by a variety of synthetic se cretagogues, of which growth hormone-releasing hexapeptide (GHRP-6) ha s been most thoroughly studied; it is thought to have actions at both pituitary and hypothalamic sites. To evaluate the central actions of t his peptide, we have studied GH release in response to direct i.c.v. i njections in anaesthetized guinea pigs. GHRP-6 (0.04-1 mu g) stimulate d GH release >10-fold 30-40 min after i.c.v. injection. The same GH re sponse required >20-fold more GHRP-6 when given by i.v. injection. GH release could also be elicited by a non-peptide GHRP analogue (L-692,5 85, 1 mu g i.c.v.), whereas a growth hormone-releasing factor (GRF) an alogue (human GRF (27)Nle(1-29)NH2, 2 mu g, i.c.v.) was ineffective. A long acting somatostatin analogue (Sandostatin, SMS 201-995, 10 mu g i.c.v.) (SMS) given 20 min before 200 ng GHRP-6 blocked GH release. Th is was unlikely to be due to a direct effect of SMS leaking out to the pituitary, since central SMS injections did not affect basal GH relea se, nor did they block GH release in response to i.v. GRF injections. We conclude that the hypothalamus is a major target for GHRP-6 in vivo . Since the GH release induced by central GHRP-6 injections can be inh ibited by a central action of somatostatin, and other data indicate th at GHRP-6 activates GRF neurones, we suggest that somatostatin may blo ck this activation via receptors known to be located on or near the GR F cells themselves. Somatostatin may therefore be a functional antagon ist of GHRP-6 acting centrally, as well as at the pituitary gland.