Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes that regulates food intake and energy expenditure. Leptin has recently been shown to play a stimulatory role on GH secretion. The aim of the present study was to investigate whether leptin regulation of GH secretion was mediated by hypothalamic neuropeptide Y (NPY). We assessed the effect of leptin administration (10 microg, i.c.v.) and/or NPY (4 microg, i.c. v.) on fasted rats. Furthermore we administered leptin antiserum (10 microl, i.c.v.), anti-NPY serum (5 microl, i.c.v.) or normal rabbit serum (10 microl, i.c.v.) to freely moving fed rats. Spontaneous GH secretion was assessed over 6 h with blood samples taken every 15 min. Fed rats treated with anti-NPY serum exhibited a normal ultradian GH rhythm. However, administration of anti-NPY serum (5 microl, i.c.v., at 120 min) completely reversed the suppression induced by antileptin serum (10 microl, i.c.v., at 0 min) on plasma GH levels (area under the curve, AUC, 168 +/- 72 vs. 1,287 +/- 430 ng/ml/6 h; p < 0.01). In fasted rats, following NPY administration, GH levels remained suppressed throughout the 6 h studied. Besides, NPY administration completely blunted leptin-induced GH secretion as assessed by the AUC (28.5 +/- 11 vs. 520 +/- 220 ng/ml/6 h; p < 0. 01). Thus, it is possible that NPY mediates the effects of leptin on GH secretion. Alternatively, leptin and NPY could act through parallel pathways to alter GH release with NPY overcoming the stimulatory effect exerted by leptin on plasma GH levels.