Pubertal hormones increase hippocampal expression of α4βδ GABA_A receptors

CA1 hippocampal expression of α4βδ GABA_A 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 (E₂) (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, E₂ 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 E₂ 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 E₂ receptor-α (ER-α). These results suggest that both the rise in circulating levels of E₂ and the decline in hippocampal THP levels at the onset of puberty trigger maximal levels of α4βδ expression in the CA1 hippocampus.