Sex and gonadal activity modify the effect of 2-hydroxyestradiol on hypothalamic GABA uptake in the rat

The aim of this study was to determine the changes induced by sex and sexual steroids on the effect of the catecholestrogen 2-hydroxyestradiol (2OHE2) upon hypothalamic GABA uptake. For this purpose we have measured [3H]-GABA uptake by crude synaptosomal fractions obtained from normal female and male rats and from ovariectomized and virilized female rats in the presence or absence of increasing concentrations (0.1 to 100 microM) of 20HE2. The results presented in this paper demonstrate that the effect of the catecholestrogen varied according to sex: it potentiated the specific [3H]-GABA uptake in female rats, whereas it clearly inhibited the uptake in male and virilized rats. The enhancing effect of the catecholestrogen was not affected by ovariectomy, but a higher specific GABA uptake was observed in the ovariectomized animals. The present study provides the first evidence that the effect of 2OHE2 on hypothalamic GABA uptake depends on sex, thus suggesting the existence of a sexual dimorphism. Further studies in this field are required to elucidate the physiological significance and the underlying mechanism of the mentioned effect.