Cocaine and Amphetamine-Regulated-Transcript Peptide Mediation of Leptin Stimulatory Effect on the Rat Gonadotropin-Releasing Hormone Pulse Generator in Vitro
[en] 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.
Gerard, Arlette ; Centre Hospitalier Universitaire de Liège - CHU > Pédiatrie
Parent, Anne-Simone ; Université de Liège - ULiège > Département des sciences cliniques > Pédiatrie
Bourguignon, Jean-Pierre ; Université de Liège - ULiège > Département des sciences cliniques > Pédiatrie
Language :
English
Title :
Cocaine and Amphetamine-Regulated-Transcript Peptide Mediation of Leptin Stimulatory Effect on the Rat Gonadotropin-Releasing Hormone Pulse Generator in Vitro
Chehab FF, Lim ME, Ronghue L. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nature Genet 1996; 12: 318-320.
Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD. A leptin missense mutation associated with hypogonadism and morbid obesity. Nature Genet 1998; 18: 213-215.
Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O'Rahilly S. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999; 341: 879-884.
Yu WH, Kimura M, Walezewska A, Karanth S, McCann SM. Role of leptin in hypothalamic-pituitary function. Proc Natl Acad Sci 1997; 94: 1023-1028.
Magni P, Vettor R, Pagano C, Calcagno A, Beretta E, Messi E, Zanisi M, Martini L, Motta M. Expression of a leptin receptor in immortalized gonadotrophin-releasing hormone-secreting neurons. Endocrinology 1999; 140: 1581-1585.
Purnelle G, Gérard A, Czajkowski V, Bourguignon JP. Pulsatile secretion of gonadotrophin-releasing hormone by rat hypothalamic explants without cell bodies of GnRII neurons. Neuroendocrinology 1997; 66: 305-312.
Bourguignon JP, Gérard A, Alvarez Gonzalez ML, Franchimont P. The neuroendocrine mechanism of onset of puberty: sequential reduction in activity of inhibitory and facilitatory N-methyl-D-aspartate receptors. J Clin Invest 1992; 90: 1736-1744.
Cunningham MJ, Clifton DK, Steinert RA. Leptin's actions on the reproductive axis: perpectives and mechanisms. Biol Reprod 1999; 60: 216-222.
Finn PD, Cunninghan MJ, Pau K-YF, Spies HG, Clifton DK, Steiner RA. The stimulatory effect of leptin on the neuroendocrine reproductive axis of the monkey. Endocrinology 1998; 139: 4652-4662.
Kalra SP, Xu B, Dube MG, Moldawer LL, Martin D, Kalra PS. Leptin and ciliary neurotropic factor (CNTF) inhibit fasting-induced suppression of luteinizing hormone release in rats: role of neuropeptide Y. Neurosci Lett 1998; 240: 45-49.
Chehab FF, Mounzih K, Lu R, Lim ME. Early onset of reproducive function in normal female mice treated with leptin. Science 1997; 275: 88-90.
Cheung CC, Thornton JE, Kuijper JL, Weigle DS, Clifton DK, Steiner RA. Leptin is a metabolic gate for the onset of puberty in the female rat. Endocrinology 1997; 138: 855-857.
Clayton PE, Gill MS, Hall CM, Tillmann V, Whatmore AJ, Price DA. Serum leptin through childhood and adolescence. Clin Endocrinol 1997; 46: 727-733.
Plant TM, Durrant AR. Circulating leptin does not appear to provide a signal for triggering the initiation of puberty in the male rhesus monkey (Macaca Mulatta). Endocrinology 1997; 138: 4505-4508.
Zamorano PL, Mahesh VB, De Sevilla LM, Chorich LP, Bhat GK, Brann DW. Expression and localization of the leptin receptor in endocrine and neuroendoerine tissues of the rat. Neuroendocrinology 1997; 65: 223-228.
Hakansson ML, Brown H, Ghilardi N, Skoda RC, Meister B. Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. J Neurosci 1998; 18: 559-572.
Kristensen P, Judge ME, Thim L, Ribel U, Christjansen KN, Wulff BS, Clausen JT, Jensen PB, Madsen OD, Vrang N, Larsen PJ, Hastrup S. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 1998; 393: 72-76.
Hartter DE, Ramirez VD. Responsiveness of immature versus adult male rat hypothalami to dibutyryl cyclic AMP- and forskolin-induced LHRH release in vitro. Neuroendocrinology 1985; 40: 476-482.
Phillips MS, Liu O, Hammond HA, Dugan V, Hey PJ, Caskey CT, Hess JF. Leptin receptor missense mutation in fatty Zucker rat. Nature Genet 1996; 13: 18-19.
