The Synergistic Effects of His-D-Trp-Ala-Trp-D-Phe- Lys-NH₂on Growth Hormone (GH)-Releasing Factor- Stimulated GH Release and Intracellular Adenosine 3',5'-Monophosphate Accumulation in Rat Primary Pituitary Cell Culture

Abstract

His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) stimulated GH release from rat primary pituitary cells in a time- and dose-dependent manner. Stimulation was observed after a 15-min, but not a 4-h, incubation. The concentrations of GHRP-6 required for half-maximal and maximal stimulation were 7 x 10(-9) and 10(-7) M, respectively. GH release induced by GHRP-6 was not affected by the addition of either naloxone or the GRF antagonist [N-Ac-Tyr1,D-Arg2]GRF-(1-29)-NH2. The latter inhibited GRF-stimulated GH release by shifting the dose-response curve to the right. His-D-Trp-D-Lys-Trp-D-Phe-Lys-NH2, an analog of GHRP-6, inhibited GH release stimulated by GHRP-6 without affecting that induced by GRF. When present together at maximal concentrations, GHRP-6 and GRF produced a synergistic effect on GH release. GHRP-6 had no effect on intracellular cAMP levels, whereas GRF increased intracellular cAMP concentrations by 3-fold. Combined treatment of pituitary cells with GRF and GHRP-6 resulted in a potentiation of the GRF-induced increase in cAMP levels. Basal GH release was reduced by 30% after pretreatment with GHRP-6 (10(-7) M) for 1 h. Pretreatment with GHRP-6 also decreased the subsequent response to GHRP-6, but not GRF. In contrast, pretreatment with GRF for 1 h had no effect on the subsequent action of GHRP-6 or GRF on GH release. The desensitization induced by GHRP-6 was completely reversed within 1 h after removal of the peptide. Results from this study indicate that GHRP-6 and GRF stimulated GH release from somatotrophs via different receptors and through discrete mechanisms.

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

“…In addition, GH release was induced by GHRP from rat pituitary cell cultures in a time-dependent manner at 0.5, 1, 2, 3 and 4 h [8]. GH release from rat pituitary cells induced by GHRP was observed after 15 min, but not after 4 h [11]. Concerning the direct action of GHRP in inducing GH release from cultured pituitary cells, the present results in cattle are in agreement with the previous reports in rats [6,8,11,12,21].…”

“…A previous study has demonstrated that GHRP synergizes with GHRH to increase GH release from rat pituitary cells [11]. It has been reported, however, that GHRP mediates its effect through a receptor and mechanisms which are distinct from those of GHRH [11]. Moreover, the effects of GHRP on GH release are at least partially mediated via the activation of protein kinase-C [12].…”

“…Nonopioid receptors for GHRP have been identified in the hypothalamus and pituitary [10]. A previous study has demonstrated that GHRP synergizes with GHRH to increase GH release from rat pituitary cells [11]. It has been reported, however, that GHRP mediates its effect through a receptor and mechanisms which are distinct from those of GHRH [11].…”

In vivo effects of the GH-releasing heptapeptide GHRP-1 in lambs

“…Although both act synergistically [4,[9][10][11]17], a GHRP antagonist inhibits the in vitro response to GHRP but not to GHRH [11,17]. GHRH raises the intracellular level of cAMP in the pituitary, whereas GHRP does not [ 17].…”

“…GHRH raises the intracellular level of cAMP in the pituitary, whereas GHRP does not [ 17]. GHRP [9,18,39].…”