Abstract
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 µg/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 acompanied
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.
Key words
Leptin - GABA - excitatory amino acids - GnRH
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Dr. Jaime A. Moguilevsky
Departamento de Fisiología
Facultad de Medicina
Universidad de Buenos Aires
Paraguay 2155
(1121) Buenos Aires
Argentina
Phone: + 541149814898
Fax: + 54 11 49 81 99 21
Email: jmoguile@fmed.uba.ar