Changes Induced by Sex Steroids in the Kinetic Properties of Hypothalamic GABA Uptake

Abstract

The aim of this study was to determine the changes induced by sex steroids in the kinetic properties of hypothalamic GABA uptake. For this purpose, we measured [³H]-GABA uptake by crude hypothalamic synaptosomal fractions obtained from intact female and male rats, orchidectomized and ovariectomized rats, and female rats treated neonatally with estrogens (“virilized” female rats) in the absence or presence of increasing concentrations of unlabelled GABA. Kinetic analysis of the uptake was performed through Eadie Hofstee plots. The specific [³H]-GABA uptake by hypothalamic crude synaptosomes varied according to the sex of the animals and the endogenous level of sex steroids. It was higher in male than in female rats. Gonadectomy resulted in a three-fold increase of the GABA uptake in both groups. Estradiol administration to ovariectomized rats reverted the high values recorded in these animals to levels below the range observed in intact rats. [³H]-GABA uptake was higher in “virilized” than in female rats. The kinetic analysis of the dose-dependent inhibition of [³H]-GABA uptake by unlabelled GABA showed the existence of both high and low affinity uptake systems in female rats and a single uptake system in male rats. Ovariectomy induced an increase in the V_max value whereas orchidectomy resulted in a lower K_m and a higher V_max compared to intact rats. In conclusion, our results show that [³H]-GABA uptake by crude synaptosomes is sexually dimorphic and depends on the hypothalamic levels of endogenous sex steroids after gonadectomy.