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 intracellular messenger pathways from those utilized by GHRH, and at the hypothalamic level where receptors for GHRP-6 have been demonstrated. This study examines the effect of GHRP-6 on GH secretion in vitro and in vivo. Lamb adenohypophysial cell cultures were subjected to a challenge with 1) 10 nM GHRH-1-29; 2) 1 microM GHRP-6; and 3) 10 nM GHRH plus 1 microM GHRP-6. Both peptides released GH, GHRP-6 being less potent than GHRH, and the GH response to GHRH and GHRP-6 not being synergistic, without statistically significant differences between GHRH+GHRP-6 and GHRH alone. In in vivo studies, six lambs received 15 microg/kg GHRH (1-29) or 15 microg/kg GHRH plus 10 microg/kg GHRP-6 and six other lambs received 100 microg/kg GHRP-6 or 3 mg/kg pyridostigmine plus 100 microg/kg GHRP-6. The results have shown that the combination of GHRH plus 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 administration of GHRP-6 plus pyridostigmine produced in a stronger GH response to GHRP-6 (100 microg/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 interactions of GHRP-6 with GHRH or pyridostigmine in releasing GH seem to indicate independent actions of these compounds. These results suggest that GHRP-6 potentiates the GH secretion stimulated by GHRH at the hypothalamic level, in these animals.
Rico
M
M
Departamento de Fisiología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
Rueda
V
V
Lorenzo
M T
MT
Núñez
A
A
De la Cruz
L F
LF
D000818:Animals; D002478:Cells, Cultured; D018678:Cholinergic Agents / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D011863:Radioimmunoassay; D012756:Sheep
D018678:Cholinergic Agents; D016895:Culture Media, Serum-Free; D006728:Hormones; D009842:Oligopeptides; D010277:Parasympathomimetics; D010446:Peptide Fragments; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C059148:somatotropin releasing hormone (1-29); D011729:Pyridostigmine Bromide