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

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 27 26increased by leptin (10 M) and CART (10 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 27 amplitude in the female. A slight but significant increase in GnRH pulse amplitude was caused by NPY (10 M) in the female. However, 26GnRH pulse amplitude was not affected by a Y5-receptor antagonist (10 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 27 anti-CART antiserum whereas it was not affected by coincubation with the NPY Y5-receptor antagonist (10 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.

The neuroendocrine timing of puberty

“…However, a number of peptidergic cell phenotypes in more caudal areas of the hypothalamus do colocalise leptin receptors, for example NPY/agoutirelated peptide (AgRP) and pro-opiomelanocortin (POMC)/CART neurons in the arcuate nucleus, and melanin concentrating hormone (MCH) and orexin neurons in the lateral hypothalamus (Hakansson et al 1988, Iqbal et al 2001b. Moreover, leptin clearly regulates the activity of multiple hypothalamic peptidergic systems implicated in the control of energy metabolism (for example MCH, NPY, CART, orexin), many of which have been shown to extend rostral projections to areas implicated in the control of GnRH secretion (Parent et al 2000). Given the profound hypogonadotrophism seen when GPR54 receptor signalling is dysfunctional (Seminara et al 2003), an intriguing possibility is that direct metabolic regulation of the GnRH secretory system is via GPR54 receptors known to be expressed in GnRH neurons (Messager et al 2005).…”

Influence of Neuropeptide – Glutamic Acid-Isoleucine (NEI) on LH Regulation

“…6 E) Experiments using in vitro preparations or intracerebroventricular injections have shown that various neurotransmitters can regulate gonadotropin release [38][39][40]. One such neurotransmitters is the cocaine-and amphetamine-regulated transcript (CART) peptide, which has been shown to increase the GnRH pulse amplitude in cycling female rats and to decrease GnRH pulse intervals in prepubertal rats [41][42][43]. These effects can be achieved through direct CART innervation of the GnRH neurons [39,40].…”

Rol' leptina v narushenii reproduktivnoy funktsii pri ozhirenii

“…Ароматазная актив-ность обнаружена в клетках околожировой соеди-нительно-сосудистой стромы и может отличаться в различных местах отложения жировой ткани [62]. Различий в уровнях андрогенов у пациентов с «простым» ожирением по сравнению с контроль-ной группой отмечено не было [72] в отличие от повышенной концентрации андростендиона, эс-трона и инсулина у женщин с центральным типом ожирения [64]. У женщин количество андростен-диона, превращаемого в эстрон, зависит от общей массы тела в процентным отношением по следую-щей схеме: 49-63 кг (1%), 63,1-91 кг (1,5%) и > 91 кг (2,3%) [62].…”