Leptin effects on pulsatile gonadotropin releasing hormone secretion from the adult rat hypothalamus and interaction with cocaine and amphetamine regulated transcript peptide and neuropeptide Y

Leptin may act as a negative feedback signal to the hypothalamic control of appetite through suppression of neuropeptide Y (NPY) secretion and stimula tion of cocaine and amphetamine regulated transcript (CART). We aimed at st udying the effects of leptin, CART and NPY on the hypothalamic control of t he pituitary-gonadal system. Pulsatile gonadotropin-releasing hormone (GnRH ) secretion was studied in vitro using retrochiasmatic hypothalamic explant s from adult rats. In the female, GnRH pulse amplitude was significantly in creased by leptin (10(-7) M) and CART (10(-6) M) irrespective of the estrus cycle phase while no such effects were seen in the male. The GnRH interpul se interval was not affected in both sexes. Passive immunoneutralization ag ainst CART caused a reduction in GnRH pulse amplitude in the female. A slig ht but significant increase in GnRH pulse amplitude was caused by NPY(10-7 M) in the female. However, GnRH pulse amplitude was not affected by a YS-re ceptor antagonist (10(-6) M) while the interpulse interval was significantl y increased as shown previously in the male. The increase in GnRH pulse amp litude caused by leptin was totally prevented by coincubation with an anti- CART antiserum whereas it was not affected by coincubation with the NPY YS- receptor antagonist (10(-7) M). In conclusion, leptin and NPY show separate permissive effects on GnRH secretion in the adult rat hypothalamus. In bot h sexes, NPY is prominently involved in the control of the frequency of pul satile GnRH secretion through the Y5 receptor subtype. Leptin causes a fema le-specific facilitatory effect on GnRH pulse amplitude which is mediated b y CART and which occurs irrespective of the estrus cycle phase. (C) 2000 El sevier Science B.V. All rights reserved.