GnRH antagonists suppress prolactin release in non-human primates

GnRH antagonists, such as Antide, are being evaluated for potential contraceptive applications. Although their contraceptive efficacy clearly results from their rapid inhibitory effects on gonadotropin release, there remains the possibility of other incidental effects. Under certain physiological conditions, the release of prolactin (Prl) appears to be temporally related to the secretion of luteinizing hormone (LH) and hence by inference to the secretion of GnRH. Here, we examined the effects of the GnRH antagonist Antide on the release of LH and Prl. Under agonadal conditions, a remarkable concordance was seen between LH and Prl pulses with up to 100% of pulses being coincident. Administration of Antide resulted in a rapid parallel decline in both LH and Prl with LH levels falling by 50% within 2 h and Prl levels falling by 30-40%. At this dose of Antide (1.0 mg/kg, sc), pulsatile release of LH and Prl continued albeit at a much reduced amplitude. The administration of a bolus of exogenous GnRH in the face of GnRHant-induced suppression resulted in prompt release of LH and Prl in all 3 monkeys. Since Antide inhibits the release of LH and Prl in a parallel fashion, and GnRH re-stimulates the release of both hormones in a parallel fashion, we conclude that the synchronous pulsatile release of LH and Prl observed in the agonadal monkey is due to a direct action of GnRH. What this action is for Prl release, and how it relates to the control of dopamine or other neuroendocrine mechanisms normally controlling the release of Prl remains unclear. It also remains to be seen whether this GnRH antagonist-induced suppression of Prl will have physiologic significance.