Effect of the GH secretagogue L-163,255 and restricted feeding time on GH pulsatility in the rat

Objective: To determine the effect of repeated treatments with the growth hormone secretagogue (GHS) L-163,255 on the pulsatile release of GH when administered in meal-fed rats before and after feeding. Design: The first group of rats (AL, n = 6) had food available ad libitum. The second (restricted, R, n = 6), third (GHSB, n = 6), and fourth (GHSA, n = 6) groups were fed from 1100 to 1400 h. Groups GHSB and GHSA were given GHS by gavage, 3.0 mg/kg L-163,255, at 1000 h (before feeding, B) and at 1500 h (after feeding, A) respectively. Three weeks after the initiation of the treatment, blood samples were collected at 10-min intervals over 6 h, and GH levels were determined. Results: In group R, the concentrations of GH were higher before feeding (17.6±2.4 ng/ml) than during feeding (11.2±1.2 ng/ml), P < 0.05. The average concentrations of the peak in response to GHS were higher when GHS was administered before (121.70±33.68 ng/ml) than after (49.67 ± 17.87 ng/ml) feeding. The mass of GH, as calculated by deconvolution analysis was also higher in the GHSB group than in the GHSA group (251.6±64.1 ng/ml per min vs 85.3±22.9 ng/ml per min respectively, P < 0.05). Conclusion: L-163,255 is effective in inducing GH release after repeated oral administration in rats. The effectiveness is greater when GHS is administered before rather than after feeding in meal-fed animals.