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

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 5α‐dihydroprogesterone in the pituitary, and this metabolite has recently been shown to deplete pituitary estrogen receptors similar to progesterone. Thus the effect of 5α‐dihydroprogesterone onstrogen‐induced prolactin release was also examined. 5α‐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 5α‐dihydroprogesterone significantly inhibited estrogen‐induced prolactin release, whereas the 0.8 mg/kg dose was ineffective. The effect of 5α‐dihydroprogesterone required estrogen priming and was blocked by the antiprogestin, RU486, suggesting progesterone receptor mediation.