Variations in energy balance can have a profound impact upon reproductive activity, an effect mediated via peripheral metabolic signals such as leptin or insulin. The overall aim of the studies described below was to better understand the hypothalamic pathways and mechanisms of action implicated in the reproductive effects of these two satiety factors. The effects of leptin to modulate reproduction depend at least partially upon hypothalamic NPY neurons of the arcuate nucleus. Using mice knockout for the Y1 subtype of NPY receptors (Y1^-/- mice), we identified a crucial role for Y1-dependent pathways downstream of NPY neurons to convey leptin signals upon GnRH neurons, the key activators of the reproductive neuroendocrine axis. A striking finding of these experiments was the observation that juvenile Y1^/- mice submitted to food restriction undergo normal sexual maturation, demonstrating the importance of Y1 for the sensing of decreasing leptin levels by these neurons. In contrast, GnRH-expressing neurons express functional insulin receptors, and insulin stimulation increases both the expression and the secretion of GnRH from cultured cells. The physiological relevance of these results is suggested by our finding that in adult male mice, circulating levels of luteinizing hormone are increased by peripheral insulin administration. Taken together, these data confirm that in addition to signalling satiety to the central nervous system, insulin stimulates the neuroendocrine reproductive axis, probably via a direct effect on hypothalamic GnRH neurons. Overall, our results provide new insights into the coordinated regulation of feeding and reproductive activity by the central nervous system.