Postpartum lactational anovulation in a nonhuman primate (Macaca fascicularis): endogenous opiate mediation of suckling-induced hyperprolactinemia.

Abstract

The physiological amenorrhea occurring in suckled females has been associated with both hypopulsatile gonadotropin secretion and hyperprolactinemia. To test whether these phenomena are opiate mediated and whether these effects are dependent on the presence of ovaries, we studied six suckled, lactating cynomolgus monkeys, three with intact ovaries and three that were ovariectomized 14 days postpartum. Frequent blood sampling (every 15 min) was performed at approximately monthly intervals using chronic venous catheters accessed remotely via a jacket and tether system. Each monkey was administered saline or naloxone (2 mg bolus then 2 mg/h) by constant infusion, in alternating 6-h blocks. During saline infusions, PRL concentrations varied markedly in a diurnal pattern with concentrations varying from 30-70 micrograms/L during the day and from 100-200 micrograms/L during the night. In both gonadal intact and ovariectomized groups of monkeys naloxone dramatically suppressed and maintained PRL concentrations at less than 20 micrograms/L irrespective of the time of day or the order of administration. The effects of naloxone on gonadotropin concentrations were much less dramatic. In gonadal-intact monkeys, no effect of naloxone was seen on pulse frequency of either FSH or LH, or on mean LH concentration, and only a slight increase was noted in mean FSH concentrations. In ovariectomized monkeys, naloxone was also without effect on pulsatile LH secretion, although mean LH concentrations were slightly higher during naloxone infusions than during saline infusions (P less than 0.05). From these results, we conclude that opiate peptides are released in response to the suckling stimulus in the cynomolgus monkey and that they mediate the effects of suckling on PRL secretion in both gonadal-intact and agonadal cynomolgus monkeys. The lack of effect of opiate blockade on gonadotropin concentrations suggests that multiple pathways may be involved with the inhibition of the GnRH pulse generator during lactational anovulation.