Biphasic gabaergic regulation of GnRH secretion in GT1 cell lines

The mouse GT1 gonadotropin-releasing hormone (GnRH) neuronal cell lines exhibit highly differentiated properties of GnRH neurons. This report investigates the direct effect of gamma-aminobutyric acid (GABA) and subtype selective GABA agonists on GnRH secretion by GT1 cells in perifusion. Treatment of GT1-1 cells with GABA (10 microM) for 100 min resulted in a biphasic release of GnRH. A rapid and sharp stimulation of GnRH secretion was followed by a sustained inhibition of GnRH secretion. During the inhibitory phase, pulses of GnRH assessed by 'cluster analysis' were totally suppressed. The GABAA receptor agonist muscimol (10 microM) stimulated a rapid but transient release of GnRH. On the other hand, treatment of GT1-1 cells with the GABAB receptor agonist baclofen (10 microM) resulted in the prolonged inhibition of GnRH secretion which returned to normal after the treatment stopped. These results demonstrate a direct biphasic effect of GABA upon GnRH release. The initial stimulation appears to be mediated via GABAA receptors, while the sustained inhibition of GnRH secretion appears to involve the activation of GABAB receptors.