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.
AN Moulas, Krieg RJ Jr, JD Veldhuis and JC Chan
K Latta, Krieg RJ Jr, S Hisano, JD Veldhuis and JC Chan
DESIGN: Deflazacort (DFZ) is a relatively new glucocorticoid that has been reported to exhibit fewer side-effects than other commonly used corticosteroids. The present study was designed to test the effects of DFZ on thymus gland involution (thymolysis), as compared with body growth and the secretory pattern of GH in the rat. Beginning at 38 days of age, male animals were treated for 8 consecutive days by s.c. injection of DFZ (0.15mg/day), cortisone (CORT) (5mg/day) or vehicle (control, CTRL). RESULTS: Both glucocorticoids had a similar thymolytic effect and caused growth failure, but the growth rate for the DFZ group was significantly higher than that of the CORT group. On day 46, pulsatile GH secretion was quantitated by blood sampling via an indwelling catheter at 10 min intervals for 6h. GH was assayed by RIA and analyzed by multiparameter deconvolution. CORT caused an increase in pulse frequency (5.8+/-0.4 (s.e.m.)) in comparison to DFZ (4.4+/-0. 4) and CTRL (3.8+/-0.3). Both glucocorticoids significantly shortened the interval between secretory bursts. In CTRL animals the interval between bursts was 69.3+/-4.5 min. In DFZ animals this was reduced to 58.5+/-7.1 min, and in CORT rats it was further reduced to 47.0+/-2.6 min. The mass of GH secreted per burst was reduced in CORT animals (52% of CTRL), while DFZ did not alter this parameter. A similar trend was observed for total GH production, with CORT causing a reduction and DFZ not affecting the secretion. CONCLUSION: Rats treated with glucocorticoid show a profound thymolytic effect, as well as important changes in growth. While CORT suppresses GH secretion and alters its pulsatile mode of release, DFZ causes a less significant alteration in the pattern of GH secretion and does not negatively affect the overall amount of GH secreted.