Long-term testosterone or diethylstilbestrol treatment affects gamma-aminobutyric acid and central-type benzodiazepine receptors but not peripheral-type benzodiazepine receptors in the female rat brain.

Abstract

Steroids have often been associated with modulation of the GABAergic system in the central nervous system, mainly in ovariectomized rats. In the present study, the effect of the synthetic estrogen diethylstilbestrol (DES) and testosterone (T) on the density of peripheral and central benzodiazepine (BZ) and gamma-aminobutyric acid (GABAA) receptors was evaluated in the frontoparietal cortex and whole cerebellum of female rats during the peripubertal period. The density of peripheral-type BZ receptors was not altered in either of these organs, whether or not treated with DES or T. The density of central BZ and GABAA receptors in either frontoparietal cortex or whole cerebellum was significantly reduced following treatment with DES or T; however, the effect of DES was much more pronounced. The similarity of the effect of T to that of DES may suggest that the effect of T is mediated at least partially by intraovarian biosynthesis of estradiol-17 beta from the exogenously administered T. Collectively, these results may suggest that in female rats during the peripubertal period, sex steroids produce a down-regulatory effect on expression of the brain GABAA/BZ complex, in contrast to their well-established up-regulatory effect in adult ovariectomized rats.