Cocaine and amphetamine-regulated-transcript peptide mediation of leptin stimulatory effect on the rat gonadotropin-releasing hormone pulse generatorin vitro

Pulsatile gonadotropin-releasing hormone (GnRH) secretion was studied in vi tro using explants of the retrochiasmatic hypothalamus from prepubertal mal e and female rats. Leptin caused a dose-dependent reduction of the GnRH int erpulse interval in both sexes. We studied the effects of cocaine- and amph etamine-regulated transcript (CART) since this peptide was shown recently t o mediate the anorectic effects of leptin in the hypothalamus. CART caused a reduction of the GnRH interpulse interval. This effect was prevented usin g an anti-CART antiserum which could partially overcome leptin stimulatory effects as well. Using hypothalamic explants from Zucker rats homozygous fo r the leptin receptor mutation (fa/fa), GnRH pulse frequency was not affect ed by leptin, while a significant acceleration was caused by the CART-pepti de. In conclusion, leptin involves the hypothalamic CART-peptide to stimula te the prepubertal GnRH pulse generator in vitro.