RESUMO
The purpose of the present study was to determine the effect of treatment with leptin on gonadotrophin secretion and hypothalamic GnRH, excitatory and inhibitory amino acids release, in prepubertal (15 days old) and peripubertal (30 days old) male rats. Rats of both ages received a single (ip) injection of 30 microg/kg leptin 60 minutes previous to sacrifice. Serum LH was determined, and the hypothalamus dissected and incubated in Earle's medium. GnRH and amino acids release were determined in the media. LH and GnRH were measured by RIA. Amino acids were assessed by HPLC-UV detection. In the two prepubertal stages, (prepubertal and peripubertal, 15 and 30 days of age respectively) leptin increased plasmatic LH levels (p < 0.01) and hypothalamic GnRH release (p < 0.01). Glutamate (GLU) release showed an increment in leptin-treated rats (p < 0.01) at both ages, while only the 30 days old rats showed an increment of the aspartate (ASP) release. GABA secretion was not modified by leptin treatment. In conclusion, the results demonstrated that leptin stimulates the LH-GnRH axis during sexual development in male rats, increasing the secretion of both hormones. The hypothalamic excitatory amino acid neurotransmitter system appears to be involved in this change.
Assuntos
Aminoácidos/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Leptina/farmacologia , Hormônio Luteinizante/sangue , Maturidade Sexual/fisiologia , Animais , Ácido Aspártico/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Ácido Glutâmico/metabolismo , Hipotálamo/efeitos dos fármacos , Masculino , Radioimunoensaio , Ratos , Ácido gama-Aminobutírico/metabolismoRESUMO
The purpose of the present study was to analyse the effect of leptin treatment on the hypothalamic release of GnRH, GABA, and the excitatory amino acids (EAA), aspartate (ASP) and glutamate (GLU) involved in NMDA neurotransmission in prepubertal (15 day old) and peripubertal (30 day old) female rats. The animals were treated with a single dose of leptin (30 microg/kg i.p.) and sacrificed 60 min later. Hypothalamic samples were incubated in Earle's medium; GnRH was determined by RIA and GLU, ASP and GABA by HPLC by UV detection. The hypothalamic release of GnRH was increased by leptin at both ages, the release being significantly higher in peripubertal than in prepubertal rats. The levels of hypothalamic GABA release were different in the two groups; whereas in prepubertal rats the hypothalamic release of GABA increased with leptin administration, the neurotransmitter release decreased in the peripubertal group. On the other hand, the release of ASP was modified only in the peripubertal group, where leptin significantly increased its hypothalamic release. No modifications in leptin-induced hypothalamic release of GLU were observed at the two ages studied. In conclusion, the results showed that leptin increased GnRH release by the hypothalamus of prepubertal and peripubertal rats. In peripubertal rats this increase was accompanied by a significant decrease in the hypothalamic release of GABA as well as an enhanced release of ASP. These results and previous reports suggest that at this stage of sexual maturation, leptin exerts an stimulatory effect on GnRH by inducing release of excitatory amino acids (ASP) and reducing release of inhibitory amino acids (GABA) involved in GnRH control. In prepubertal rats the stimulating effect of the adipocyte hormone on GnRH appears to be related to its stimulative action on GABA which at this age increases GnRH release.