Effects of progesterone metabolites on gonadotrophin secretion

Abstract

The experiments described where planned to validate the hypothesis that dihydroprogesterone (DHP) and 5alpha-pregnan-3X-ol-20-one (3alpa-ol) might represent the mediators of progesterone (P) actions in the structures where the steroid exerts its feedback effects on luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion. 5alpha-Pregon-3beta-ol-20-one (3beta-ol) was also studied. This is the 3beta epimer of 3alpha-ol. These steroids were given to castrated estrogen-pretreated female rats and to castrated female rats without the estrogen pretreatment. Serum LH concentrations were determined by the double-antibody radioimmunoassay procedure. An antiserum against ovine LH and pure ovine LH iodinated with iodine-131 were used. Values were expressed in terms of NIH-LH-S17. FSH was measured using the NAIMD-RAT-FSH radioimmunoassy kit. Serum LH levels have been shown to be depressed by the injection of ethinyl estradiol (EE). The injection of P on Day 5 of estrogen priming more than doubled the serum levels of LH. Both 3alpha-ol and 3beat-ol increased serum levels of LH as much as P did. DHP was less effective. The 3beta-ol was most effective. Elevated levels of FSH found after ovariectomy were depressed by 5 daily injections of EE. DHP 3alpah-ol and 3beta-ol all exerted a stimulating effect on FSH release but less prnounced than that of P. P did not inhibit LH release but DHP 3alpha-ol and 3beta-ol did. P and 3beta-ol did not diminish serum levels of FSH in castrated female rats but DHP and 3alpha-ol did. Results suggest that P exerts its facilitatory effects on gonadotropin secretion after local conversion into DHP and particularly 3alpha-ol. That the central mechanisms that control LH and FSH secretion are not identical is indicated by the relative efficiency of the different metabolites of P.