Interaction of Progesterone with Testosterone and Dihydrotestosterone on Follicle-Stimulating Hormone Release by Cultures of Rat Anterior Pituitary Cells

Abstract

Cultures of rat anterior pituitary cells were utilized to examine the effects of testosterone, dihyrdotestosterone and progesterone alone and the interaction of progesterone with these androgens on FSH release. Four day cultures were incubated with the steroids for 48 h to examine their effects on basal FSH release and were then challenged for 6 h with 5 .times. 10-10 M LHRH, the approximate concentration required to induce half-maximal FSH release (EC50), to assess the effects of these steroids on LHRH-induced FSH release. Incubation of cultures with either testosterone, dihydrotestosterone or progesterone stimulated 48 h basal FSH release with EC50 of 8.6 .times. 10 -10 M, 2.2 .times. 10-10 M and 6.4 .times. 10-10 M, respectively. Progesterone (10-6 M) was not synergistic nor antagonistic with either testosterone or dihyrotestosterone in stimulating 48 h basal FSH release. Neither testosterone nor dihydrotestosterone altered LHRH-induced FSH release but progesterone(.ltoreq. 10-7 M) had a stimulatory effect. The stimulatory effect of progesterone on LHRH-induced FSH release was partially reversed by high concentrations (.gtoreq. 10-8 M) of either testosterone or dihydrotestosterone. Each of these 3 steroids increased the total FSH content of culture dishes, suggesting stimulation of FSH synthesis. Progesterone was slightly synergistic with dihydrotestosterone but not with testosterone, in stimulating total FSH. Because dihydrotestosterone was .apprx. 4-fold more potent than testosterone in stimulating basal FSH release, the effect of testosterone was examined in the presence of heparin, a substance which may be used to inhibit steroid 5.alpha.-reductase activity. Unexpectedly, the addition of 1000 U/ml heparin increased 48 h basal, testosterone- and LHRH-induced FSH release.