Estrogen Regulation of GABA Transmission in Rat Preoptic Area

Abstract

The medial preoptic area represents a brain region where gonadal steroids act upon classical nuclear receptors to alter brain function. Of all the neuronal phenotypes shown to express estrogen receptors in the preoptic area, GABA neurones are the most abundant and known to be located in several nuclei of the medial preoptic area. Investigators utilising techniques capable of assessing endogenous GABA levels have shown that estrogen increases both basal and stimulated extracellular GABA concentrations within the preoptic area. Experiments have also shown that estrogen is able to modulate the actions of noradrenaline upon preoptic GABA neurones. The precise nature of estrogen’s stimulatory influence on preoptic GABA concentrations is not understood fully but appears to involve changes in both the release and reuptake of GABA. As estrogen does not influence glutamic acid decarboxylase activity or gene expression in the preoptic area, the subcellular mechanism(s) through which estrogen enhances GABA release remain unknown. Recent investigations indicate that estrogen upregulates transcription of the GAT-1 GABA transporter gene in the preoptic area, and that this may contribute the stimulatory effect of estrogen on extracellular GABA concentrations. Further studies have identified effects of estrogen on GABAA receptor expression and ligand binding and, together with the above observations, demonstrate a coordinated and multifaceted upregulation of the preoptic GABA network by estrogen. It is suggested that estrogen acts directly upon GABA neurones expressing estrogen receptors to alter the dynamics of inhibitory transmission within specific neuronal networks of the preoptic area. This is likely to be of functional significance to the “feedback” influence of estrogen on the neural regulation of reproduction.