IN-VIVO EFFECTS OF THE GH-RELEASING HEPTAPEPTIDE GHRP-1 IN LAMBS

The novel synthetic growth hormone-releasing heptapeptide GHRP-1 is re ported to be more potent than growth hormone-releasing hormone (GHRH) in eliciting GH release in vivo in rats and man. However, in ovine pit uitary cells in primary culture in a perifusion system, GHRP-1 was 10- fold less active than GHRH. The purpose of this work was to study the effect of GHRP-1 in sheep in vivo. Ovine GH release stimulated by eith er GHRP-1 or GHRH(1-29)NH2, in eight pre-ruminant lambs, was determine d. GHRP-1 was administered at doses of 1.2, 2.4 and 6 nmole/kg by i.v. bolus, and GHRH(1-29)NH2 at 0.3 nmole/kg. Mean +/- s.e.m. peak GH lev els in the plasma after injection of saline, 1.2, 2.4, 6 nmole/kg GHRP -1 and 0.3 nmole/kg GHRH were 2.2 +/- 0.9, 9.3 +/- 2.5, 8.8 +/- 2.4, 3 5.1 +/- 5.8 and 51.6 +/- 10.5 ng/mL, respectively. As spontaneous 20 n g/mL peaks were observed, only peaks above this level can be considere d as significant. The highest dose of GHRP-1 (6 nmole/kg) elicited oGH release, but its action was surpassed by GHRH 0.3 nmole/kg. Furthermo re GHRP-1 and GHRH appear to behave inversely when response amplitudes are considered. Animals exhibiting a strong reaction to GHRH-1, show a correspondingly weak reaction to GHRH and vice-versa. This may refle ct differences in intracellular mechanisms at the pituitary level. Our data support the results in vitro that in sheep GHRP-1 is a weaker st imulant of GH secretion than GHRH. (C) Inra/Elsevier, Paris.