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
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Abstract
Leptin may act as a negative feedback signal to the hypothalamic control of appetite
through suppression of neuropeptide Y (NPY) secretion and stimulation of cocaine and
amphetamine regulated transcript (CART). We aimed at studying the effects of leptin,
CART and NPY on the hypothalamic control of the pituitary-gonadal system. Pulsatile
gonadotropin-releasing hormone (GnRH) secretion was studied in vitro using retrochiasmatic
hypothalamic explants from adult rats. In the female, GnRH pulse amplitude was significantly
increased 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 interpulse interval was
not affected in both sexes. Passive immunoneutralization against CART caused a reduction
in GnRH pulse amplitude in the female. A slight 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 Y5-receptor antagonist (10(-6) M) while the interpulse interval
was significantly increased as shown previously in the male. The increase in GnRH
pulse amplitude caused by leptin was totally prevented by coincubation with an anti-CART
antiserum whereas it was not affected by coincubation with the NPY Y5-receptor antagonist
(10(-7) M). In conclusion, leptin and NPY show separate permissive effects on GnRH
secretion in the adult rat hypothalamus. In both sexes, NPY is prominently involved
in the control of the frequency of pulsatile GnRH secretion through the Y5 receptor
subtype. Leptin causes a female-specific facilitatory effect on GnRH pulse amplitude
which is mediated by CART and which occurs irrespective of the estrus cycle phase.