Differential role of melanocortins in mediating leptin's central effects on feeding and reproduction

Leptin set-yes as a humoral link coupling the status of energy reserves to the functional activity of the reproductive system. Leptin is thought to ac t through melanocortinergic pathways in the brain to regulate ingestive beh aviors; however, whether melanocortins mediate leptin's actions on the neur oendocrine-reproductive axis is unknown. We tested this hypothesis first by determining whether the effects of leptin on feeding behavior and reproduc tion in the ob/ob mouse could be blocked by the melanocortin receptor (MC-R ) antagonist SHU9119 and second, by examining the effects of the MC-R agoni st MTII on feeding and the endocrine-reproductive system. Administered by i ntracerebroventricular injections, leptin inhibited food intake, raised pla sma gonadotropin levels, and increased seminal vesicle weights compared wit h controls; SHU9119 (intracerebroventricularly) attenuated leptin's effects on food intake and body weight but did not alter leptin's stimulatory effe ct on the reproductive axis, MTII (intracerebroventricularly and intraperit oneally) decreased food intake and increased body temperature compared with controls but had no effect on the reproductive-endocrine axis. These resul ts suggest that although leptin acts centrally through melanocortinergic pa thways to inhibit ingestive behaviors and stimulate metabolism, leptin's ac tivational effect on the reproductive axis is likely to be mediated by othe r, unknown neuroendocrine circuits.