Regulation of GABA transporter activity and mRNA expression by estrogen in rat preoptic area

This study has examined whether estrogen regulates GABA transporter synthesis and activity in the female rat brain. In the first experiment in situ hybridization studies examined the effects of ovariectomy on cellular GABA transporter-1 (GAT-1) mRNA content. A 25% decrease in GAT-1 mRNA expression was detected within the medial preoptic area (MPOA) but not the parietal cortex, magnocellular preoptic nucleus (Mg-POA) or caudate-putamen (C-P). Estrogen replacement for 7 d returned GAT-1 mRNA content of MPOA cells to levels observed in intact rats. In the second experiment, the effect of increased brain GABA concentrations on GAT-1 mRNA expression was investigated by treating rats with gamma-vinyl GABA, a GABA-transaminase inhibitor. Although resulting in a twofold increase in tissue GABA content, in situ hybridization experiments revealed no changes in GAT-1 transcript expression. A third series of experiments examined GABA transporter activity in vitro using a 3H GABA uptake assay in MPOA, cortex, and C-P punches. Nipecotic acid (10 microM) reduced specific 3H GABA uptake in all three brain regions while 100 microM beta-alanine only reduced uptake in the MPOA. Estrogen treatment for 7 d resulted in a significant increase in 3H GABA uptake in the MPOA but not the cortex or C-P. The presence of a putative estrogen response element in the GAT-1 gene and the effects demonstrated here on GAT-1 mRNA content and GABA transporter activity indicate that estrogen may influence GAT-1 gene transcription to alter GABA transporter function within the MPOA but not the C-P or cortex.