Modulation of GABA A Receptors and Neuropeptide Secretion by the Neurosteroid Allopregnanolone in Posterior and Intermediate Pituitary

A number of neurosteroids bind to GABA A receptors and alter their responsiveness to neurotransmitters. Considerable effort has been devoted to understanding how this form of receptor modulation alters inhibitory synaptic function. Neurosteroid‐sensitive GABA A receptors have also been demonstrated in many endocrine cells, but little is known about how neurosteroids modulate the release of hormones. Here, the action of allopregnanolone, a neurosteroid that enhances GABA A receptor‐mediated responses, was investigated in posterior pituitary nerve terminals and intermediate pituitary endocrine cells. Patch clamp recordings showed that GABA‐evoked currents were enhanced to similar degrees and with similar concentration dependences in both locations. An organ bath preparation of the neurointermediate lobe was used to investigate drug effects on secretion of vasopressin and α‐melanocyte stimulating hormone. GABA increased the basal release of vasopressin and α‐melanocyte stimulating hormone from the posterior and intermediate pituitary lobe, respectively, an effect that could be blocked by picrotoxinin. Vasopressin release evoked by electrical stimulation was also examined, and a small statistically significant inhibition by 5 μM GABA was observed. Allopregnanolone increased the basal release of vasopressin, and this effect was blocked by the GABA A receptor antagonist picrotoxinin. Allopregnanolone had no effect in conjunction wıth GABA. In contrast to the posterior lobe, allopregnanolone had no effect on release from the intermediate lobe. Thus, allopregnanolone in physiological relevant concentrations modulates GABA A receptors in both the posterior and intermediate lobes, but only affects hormone release in the posterior lobe.