Pubertal hormones increase hippocampal expression of α4βδ GABA receptors.

CA1 hippocampal expression of α4βδ GABA receptors (GABARs) increases at the onset of puberty in female mice, an effect dependent upon the decline in hippocampal levels of the neurosteroid THP (3α-OH-5α-pregnan-20-one) which occurs at this time. The present study further characterized the mechanisms underlying α4βδ expression, assessed in vivo. Blockade of pubertal levels of 17β-estradiol (E) (formestane, 0.5 mg/kg, i.p. 3 d) reduced α4 and δ expression by 75-80% (P < 0.05) in CA1 hippocampus of female mice, assessed using Western blot techniques. Conversely, E administration increased α4 and δ expression by 50-100% in adults, an effect enhanced by more than 2-fold by concomitant administration of the 5α-reductase blocker finasteride (50 mg/kg, i.p., 3d, P < 0.05), suggesting that both declining THP levels and increasing E levels before puberty trigger α4βδ expression. This effect was blocked by ICI 182,780 (20 mg/kg, s.c., 3 d), a selective blocker of E receptor-α (ER-α). These results suggest that both the rise in circulating levels of E and the decline in hippocampal THP levels at the onset of puberty trigger maximal levels of α4βδ expression in the CA1 hippocampus.