Further Evidence for Cholinergic Control of Gonadotropin and Prolactin Secretion 1

Abstract

Summary

Ovariectomized adult rats were injected with 10 μg of estradiol benzoate sc and 48 hr later with cholinergic drugs sc between 8:30 and 9:30 AM. Either pilocarpine HCl (5 or 50 mg/kg body weight) or eserine SO₄ (0.5 mg/kg) produced a drastic decrease in plasma LH and prolactin at 1/2 and 1 1/2 hr postinjection which was followed at 6 hr by increased titers of both hormones in plasma. By contrast, plasma FSH remained unchanged in the drug-injected animals except for an increase above the initial value at 6 hr which was similar to that observed in saline-injected controls. Atropine SO₄ (20 mg/kg, sc) but not atropine methyl nitrate reduced the biphasic effect of pilocarpine on both LH and prolactin release. Since atropine methyl nitrate cannot pass the blood brain barrier, this indicates that the drugs were presumably acting on CNS muscarinic receptors to produce their effects on pituitary hormone release. Sensitivity of the pituitary to synthetic LH-releasing factor (sLRF) was evaluated in pilocarpine-treated animals. Sensitivity was unchanged during the period immediately after injection of the drug, at a time that plasma LH was lowered, but was increased in the afternoon at the time of the elevation in plasma LH. The results suggest that the immediate response to muscarinic drugs is a suppression in the release of both LH and prolactin and that this is superseded after a delay by an increased release, which is associated with an increased responsiveness of the pituitary to sLRF. The increased release occurring 6 hr after injection of the drug may be a secondary result of the earlier suppression of hormone release.