Gonadotropin-Releasing Hormone Release from the Rat Hypothalamus: Dependence on Membrane Depolarization and Calcium Influx*

Release of gonadotropin-releasing hormone (GnRH) was studied by incubating individual rat hypothalami for 60 min, after a 30-min preincubation period, and measuring GnRH in the medium by immunoassay. During the 1 h of incubation, endogenous GnRH release was linear and exogenous GnRH was not destroyed. Membrane depolarization produced by increasing the medium potassium concentration to 60 mM increased GnRH release to 200-500% of control. Membrane depolarization produced by adding 10(-5) or 10(-4) M ouabain increased GnRH release to 200% of control. Melatonin (10(-7) M) and prostaglandin E2 (4 X 10(-4) M) Aslo stimulated GnRH release to 200% and 170% of control, respectively. Inhibition of calcium influx by omission of medium calcium and addition of 0.05 M EDTA reduced GnRH release to 50% of control. Both no calcium-EDTA medium and verapamil (10(-5) M) prevented the stimulation of GnRH release by 60 mM potassium, 10(-3) M melatonin, and 4 X 10(-4) M prostaglandin E2. We conclude that hypothalamic GnRH release depends on membrane depolarization and calcium influx, as does the secretion of hormones from other endocrine tissues.