Leptin increases in vivo GH responses to GHRH and GH-releasing peptide-6 in food-deprived rats

Background: Leptin has recently been shown to have a stimulatory effect on basal GH secretion. However, the mechanisms by which leptin exert this effect are not yet clear. GHRH and GH-releasing peptide (GHRP)-6 are the two most potent GH secretagogues described to date. Objective: To determine if leptin could also enhance in vivo GH responses to a maximal dose of GHRH. Design: Leptin (10 mu g i.c.v.) or vehicle was administered at random before GHRH (10 mu g/kg i.v.) or GHRP-6 (50 mu g/kg i.v.), to freely-moving rats with food available ad libitum and to (48 h) food-deprived rats. Methods: Leptin and GH concentrations were measured by radioimmunoassay. Comparison between the different groups was assessed by the Mann-Whitney test. Results: In comparison with fed rats, food-deprived rats showed a marked decrease in GH responses to GHRH as assessed by the area under the curve (5492 +/- 190 ng/ml in fed rats and 1940 +/- 128 ng/ml in fasted rats; P < 0.05) and GHRP-6 (3695 +/- 450 in fed rats and 1432 +/- 229 in fasted rats; P < 0.05). In comparison with its effects in vehicle-treated rats, leptin administered to food-deprived rats markedly increased GH responses to both GHRH (6625 +/- 613 ng/ml; P < 0.05) and GHRP-6 (5862 +/- 441 ng/ml; P < 0.05). Conclusions: These data suggest that the blunted GH response to GHRH and GHRP-6 in food-deprived rats is a functional and reversible state, and that the decreased leptin concentrations could be the primary defect responsible for the altered GH secretion in food-deprived rats.