Effect of growth hormone-releasing peptide 1-6 on GH secretion-stimulated by GHRH and pyridostigmine in lambs

The GHRP-6 seems to act at a pituitary site, activating different intracell ular messenger pathways from those utilized by GHRH, and at the hypothalami c level where receptors for GHRP-6 have been demonstrated. This study exami nes the effect of GHRP-6 on GH secretion in vitro and in vivo. Lamb adenohy pophysial cell cultures were subjected to a challenge with 1) 10 nM GHRH-1- 29; 2) 1 mu M GHRP-6; and 3) 10 nM GHRH plus I mu M GHRP-6. Both peptides r eleased GH, GHRP-6 being less potent than GHRH, and the GH response to GHRH and GHRP-6 not being synergistic, without statistically significant differ ences between GHRH+GHRP-6 and GHRH alone. In in vivo studies, six lambs rec eived 15 mu g/kg GHRH (1-29) or 15 mu g/kg GHRH plus 10 mu g/kg GHRP-6 and six other lambs received 100 mu g/kg GHRP-6 or 3 mg/kg pyridostigmine plus 100 mu g/kg GHRP-6. The results have shown that the combination of GHRH plu s GHRP-6, at low doses, causes higher GH peak (p < 0.05) and higher GH area under curve (p < 0.05) with respect to administration of GHRH alone. The a dministration of GHRP-6 plus pyridostigmine produced in a stronger GK respo nse to GHRP-6 (100 mu g/kg) in the amplitude of the GH peak (p < 0.001) and in the area under the GH response curve (p < 0.001). The complementary int eractions of GHRP-6 with GHRH or pyridostigmine in releasing GH seem to ind icate independent actions of these compounds. These results suggest that GH RP-6 potentiates the GH secretion stimulated by GHRH at the hypothalamic le vel, in these animals.