GH-releasing peptide-6 overcomes refractoriness of somatotropes to GHRH after feeding.
After a meal, somatotropes are temporarily refractory to growth hormone-releasing hormone (GHRH), the principal hormone that stimulates secretion of growth hormone (GH). Refractoriness is particularly evident when free access to feed is restricted to a 2-h period each day. GH-releasing peptide-6 (GHRP-6), a synthetic peptide, also stimulates secretion of GH from somatotropes. Because GHRH and GHRP-6 act via different receptors, we hypothesized that GHRP-6 would increase GHRH-induced secretion of GH after feeding. Initially, we determined that intravenous injection of GHRP-6 at 1, 3 and 10 microg/kg body weight (BW) stimulated secretion of GH in a dose-dependent manner. Next, we determined that GHRP-6- and GHRH-induced secretion of GH was lower 1 h after feeding (22.5 and 20 ng/ml respectively) than 1 h before feeding (53.5 and 64.5 ng/ml respectively; pooleds.e.m.=8.5). However, a combination of GHRP-6 at 3 microg/kg BW and GHRH at 0.2 microg/kg BW synergistically induced an equal and massive release of GH before and after feeding that was fivefold greater than GHRH-induced release of GH after feeding. Furthermore, the combination of GHRP-6 and GHRH synergistically increased release of GH from somatotropes cultured in vitro. However, it was not clear if GHRP-6 acted only on somatotropes or also acted at the hypothalamus. Therefore, we wanted to determine if GHRP-6 stimulated secretion of GHRH or inhibited secretion of somatostatin, or both. GHRP-6 stimulated secretion of GHRH from bovine hypothalamic slices, but did not alter secretion of somatostatin. We conclude that GHRP-6 acts at the hypothalamus to stimulate secretion of GHRH, and at somatotropes to restore and enhance the responsiveness of somatotropes to GHRH.
McMahon
C D
CD
Department of Animal Science, Michigan State University, East Lansing, Michigan 48824-1225, USA. chris.mcmahon@agresearch.co.nz
Chapin
L T
LT
Radcliff
R P
RP
Lookingland
K J
KJ
Tucker
H A
HA
D000818:Animals; D019540:Area Under Curve; D002417:Cattle; D002478:Cells, Cultured; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004435:Eating / Q000502:physiology*; D013006:Growth Hormone / Q000032:analysis / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D016018:Least-Squares Analysis; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism; D013268:Stimulation, Chemical; D013997:Time Factors
D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone