BIPHASIC GABAERGIC REGULATION OF GNRH SECRETION IN GT(1) CELL-LINES

The mouse GT(1) gonadotropin-releasing hormone (GnRH) neuronal cell li nes exhibit highly differentiated properties of GnRH neurons. This rep ort investigates the direct effect of gamma-aminobutyric acid (GABA) a nd subtype selective GABA agonists on GnRH secretion by GT(1) cells in perifusion. Treatment of GT(1-1) cells with GABA (10 mu M) for 100 mi n resulted in a biphasic release of GnRH. A rapid and sharp stimulatio n of GnRH secretion was followed by a sustained inhibition of GnRH sec retion. During the inhibitory phase, pulses of GnRH assessed by 'clust er analysis' were totally suppressed. The GABA(A) receptor agonist mus cimol (10 mu M) stimulated a rapid but transient release of GnRH. On t he other hand, treatment of GT(1-1) cells with the GABA(B) receptor ag onist baclofen (10 mu M) 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 GABA(A) receptors , while the sustained inhibition of GnRH secretion appears to involve the activation of GABA(B) receptors.