INTERACTION BETWEEN LEPTIN AND NEUROPEPTIDE-Y ON IN-VIVO GROWTH-HORMONE SECRETION

Leptin, the product of the ob gene, is a recently discovered hormone s ecreted by adipocytes that regulates food intake and energy expenditur e. Leptin has recently been shown to play a stimulatory role on GH sec retion. 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 mu g, i.c .v.) and/or NPY (4 mu g, i.c.v.) on fasted rats. Furthermore we admini stered leptin antiserum (10 mu l, i.c.v.), anti-NPY serum (5 mu l, i.c .v.) or normal rabbit serum (10 mu l, i.c.v.) to freely moving fed rat s. Spontaneous GH secretion was assessed over 6 h with blood samples t aken every 15 min. Fed rats treated with anti-NPY serum exhibited a no rmal ultradian GH rhythm. However, administration of anti-NPY serum (5 mu l, i.c.v., at 120 min) completely reversed the suppression induced by antileptin serum (10 mu l, 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 remain ed 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 possibl e that NPY mediates the effects of leptin on GH secretion. Alternative ly, leptin and NPY could act though parallel pathways to alter GH rele ase with NPY overcoming the stimulatory effect exerted by leptin on pl asma GH levels.