Dose-Related Effects of Progesterone and 5 Alpha-Dihydroprogesterone upon Estrogen-Induced Prolactin Release

Abstract Previous work from our laboratory has shown that progesterone causes a rapid reduction of pituitary nuclear estrogen receptors. This effect is accompanied by a loss of estrogen action such as estrogen-induced progesterone receptor synthesis and prolactin release. Recent work has demonstrated that the effect of progesterone on estrogen receptor depletion is dose-related. Therefore the purpose of this study was to examine the effect of different doses of progesterone upon estrogen-induced prolactin release. Progesterone exhibited a multiphasic effect on estrogen-induced prolactin release. The 0.8 mg/kg body wt and 3.2 mg/kg body wt doses of progesterone significantly inhibited estrogen-induced prolactin release, whereas the intermediate dose, 2.0 mg/kg, was without effect. Progesterone is rapidly metabolized to 5alpha-dihydroprogesterone in the pituitary, and this metabolite has recently been shown to deplete pituitary estrogen receptors similar to progesterone. Thus the effect of 5alpha-dihydroprogesterone onstrogen-induced prolactin release was also examined. 5alpha-dihydroprogesterone was found to exhibit a multiphasic effect similar to progesterone in inhibiting estrogen-induced prolactin release. The 0.4 mg/kg and 2.0 mg/kg doses of 5alpha-dihydroprogesterone significantly inhibited estrogen-induced prolactin release, whereas the 0.8 mg/kg dose was ineffective. The effect of 5alpha-dihydroprogesterone required estrogen priming and was blocked by the antiprogestin, RU486, suggesting progesterone receptor mediation.