Regulation of His-dTrp-Ala-Trp-dPhe-Lys-NH2 (GHRP-6)-lnduced GH Secretion in the Rat

Abstract

His-dTrp-Ala-Trp-dPhe, Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-response and specific manner in several species and that may well be related to an endogenous compound of similar structure. The aim of this study was to investigate the in vivo GH responses to GHRP-6 in pentobarbital anesthetized rats. Specifically and in order to avoid the influence of endogenous GHRH and somatostatin secretion we studied the GH responses to GHRP-6 in animals with surgical ablation of the hypothalamus, confirmed by histological assessment, as well as in hypophysectomyzed-transplanted rats bearing two hypophyses under the renal capsule. Since it has been previously reported that rats pretreated with GHRH (10 µg/kg i.p. every 12 h for 15 days) rather than saline-treated rats have greater GH responses to acutely administered GHRH, we compared the self-potentiating effect of chronic GH pretreatment with GHRP-6 (10 µg/kg i.p. every 12 h). Furthermore we also studied the influence of estrogens, glucocorticoids, free fatty acids (FFA) and bombesin on somatotroph responsiveness to GHRP-6 in intact rats. We found a greater GH response to GHRP-6 in rats that underwent a surgical ablation of the hypothalamus 36 h prior to the test than in sham-operated rats. A direct stimulatory effect of GHRP-6 on in vivo GH secretion was demonstrated by a clear GH response to GHRP-6 in hypophysectomyzed-transplanted rats. In addition, we found a similar response whether the animals were pretreated with GHRH or GHRP-6 over the previous 2 weeks. Finally, we found that both estrogen- and testosterone-treated rats have greater GH responses to GHRP-6 than untreated rats. On the other hand, chronic dexa-methasone administration, acute elevation of circulating FFA levels and bombesin administration markedly inhibited GH responses to GHRP-6. In contrast to the effects exerted on GH responses to GHRP-6 estrogen administration led to a decrease in GH responses to GHRH while dexamethasone did not affect the GH responses to GHRH, highlighting a differential regulation of these hormones on somatotroph responsiveness to these peptides.

Effect of Growth Hormone (GH)-Releasing Peptide (GHRP) on the Release of GH from Cultured Anterior Pituitary Cells in Cattle.

“…ing effects could be seen at doses as low as 10-" M. GHRP has been reported to release GH in a dose-response and specific manner in a number of different species, including the rat, sheep, calf, and chicken [6,19]. The activity of GHRP in releasing GH was observed when administered directly into the gastrointestinal tract in rats, dogs and monkeys [27].…”

GH and cortisol rebound rise during and following a somatostatin infusion: studies in dogs with the use of a GH-releasing peptide

“…Previous studies in humans have shown that hypothalamo-pituitary disconnection completely abolished the ACTH-and cortisol-releasing activity of GHRPs, whereas the GH-releasing activity was partially preserved (Mallo et al 1993, Hickey et al 1996. Thus, granted that the GH-releasing activity of GHRP is the result of a dual activation at both pituitary and hypothalamic sites (Müller et al 1999), the stimulation of ACTH and cortisol secretion would be instead fully dependent on CNS-mediated mechanisms.…”

The GH, prolactin, ACTH and cortisol responses to Hexarelin, a synthetic hexapeptide, undergo different age-related variations

“…It has been hypothesized that they act concomitantly at the pituitary and the hypothalamic level (14), probably antagonizing somatostatinergic activity and facilitating the activity of GHRH-secreting neurons (15)(16)(17). The evidence that the GH response to GHRPs is strongly reduced, though not lost, in the presence of hypothalamo-pituitary disconnection (14,(18)(19)(20) suggests that the functional integrity of the hypothalamo-pituitary unit is needed for the full GH-releasing activity of GHRPs, and that the hypothalamic action has a major role.…”