THE GH, PROLACTIN, ACTH AND CORTISOL RESPONSES TO HEXARELIN, A SYNTHETIC HEXAPEPTIDE, UNDERGO DIFFERENT AGE-RELATED VARIATIONS

Hexarelin (HEX) is a synthetic growth hormone-releasing peptide (GHRP) which acts on specific receptors at both the pituitary and the hypoth alamic level to stimulate GH release in an age-dependent manner. Like other GHRPs, HEX possesses also prolactin (PRL) and ACTH/cortisol-rele asing activity, similar to that of human corticotropin-releasing hormo ne (hCRH). The mechanisms underlying the stimulatory effect of GHRPs o n lactotrope and corticotrope secretion are even less clear and the in fluence of age on these endocrine activities of GHRPs is unknown, To c larify this point we studied the GH, PRL, ACTH and cortisol responses to the maximal effective dose of HEX (2.0 mu g/kg i.v.) in: 12 prepube rtal children (Pre-C, 8 male, 4 female, age 5.8-12.1 years); 12 pubert al normal short children (Pub-C, 5 male, 7 female, age 9.7-15.5 years, pubertal stage II-TV); 20 normal young adults (Young, 6 males, 14 fem ales, age 23-32 years); and in 16 normal elderly people (Elderly, 5 ma le, 11 female, age 66-81 years). The GH response to HEX was clear in P re-C (0-120 min area under curve, mean+/-S.E.M. 769.5+/-122.2 mu gmin /l) but strikingly increased (P<0.001) in Pub-C (1960.2+/-283.5 mu gm in/l). The HEX-induced GH rise in Young (1829.7+/-243.1 mu gmin/l) pe rsisted similar to that in Pub-C, but decreased in Elderly (951.1+/-23 2.9 mu gmin/l, P<0.005); the latter was, in turn, similar to that in Pre-C. HEX induced a significant PRL increase which, however, showed n o age-related variations, being similar in Pre-C (512.1+/-88.0 mu gmi n/l), Pub-C (584.0+/-106.0 mu gmin/l), Young (554.9+/-56.0 mu g*min/l ) and Elderly (523.9+59.6 pgminil). The ACTH-releasing activity of HE X was present in Pre-C (1356.6+/-204.9 mu gmin/ml) and was clearly en hanced (P<0.02) in Pub-C (2253.5+/-242.8 pgmin/ml). The ACTH rise aft er HEX in Young (1258.1+/-141.2 mu gmin/ml) was lower (P<0.02) than t hat in Pub-C and similar to that in Pre-C, while the ACTH response to HEX in Elderly (1386.5+/-340.1 mu gmin/ml) showed a further trend tow ard increase, being similar to that in Pub-C. On the other hand, the c ortisol response to HEX showed no significant age-related variations, being not different in Pre-C (7747.2+/-1031.6 mu gmin/l), Pub-C (6106 .0+/-862.9 mu gmin/l), Young (6827.5+/-509.6 mu g*min/l) and Elderly (7950.6+/-658.3 mu gmin/l). In conclusion, our present data demonstra te that in humans the GH-and ACTH-releasing activities of HEX undergo different age-related variations, while its PRL-releasing activity is not dependent on age. These findings suggest that actions at different levels and/or on different receptor subtypes mediate the different ag e-related hormonal effects of GHRPs.