Cocaine and amphetamine-regulated-transcript peptide mediation of leptin stimulatory effect on the rat gonadotropin-releasing hormone pulse generator in vitro.
Pulsatile gonadotropin-releasing hormone (GnRH) secretion was studied in vitro using explants of the retrochiasmatic hypothalamus from prepubertal male and female rats. Leptin caused a dose-dependent reduction of the GnRH interpulse interval in both sexes. We studied the effects of cocaine- and amphetamine-regulated transcript (CART) since this peptide was shown recently to mediate the anorectic effects of leptin in the hypothalamus. CART caused a reduction of the GnRH interpulse interval. This effect was prevented using an anti-CART antiserum which could partially overcome leptin stimulatory effects as well. Using hypothalamic explants from Zucker rats homozygous for the leptin receptor mutation ( fa/fa), GnRH pulse frequency was not affected by leptin, while a significant acceleration was caused by the CART-peptide. In conclusion, leptin involves the hypothalamic CART-peptide to stimulate the prepubertal GnRH pulse generator in vitro.
Lebrethon
M C
MC
Developmental Neuroendocrinology Unit, Division of Ambulatory Pediatrics and Adolescent Medicine, Department of Pediatrics, University of Liège, CHU Sart Tilman, Liège, Belgium. Marie-Christine.Lebrethon@chu.ulg.ac.be
Vandersmissen
E
E
Gérard
A
A
Parent
A S
AS
Bourguignon
J P
JP
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D002352:Carrier Proteins; D020738:Leptin; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D007987:Gonadotropin-Releasing Hormone