Aryl hydrocarbon receptor (AhR)-linked inhibition of luteal cell progesterone secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin treated cells

In this study, we tested firstly, the hypothesis that decrease of progester one secretion by luteal cells under the influence of 2,3,7,8-tetrachlorodib ezo-p-dioxin (TCDD) is due to influence on specific enzymatic steps in the biosynthetic pathway of steroidogenesis and secondly, involvement of aryl h ydrocarbon receptor (AhR) or estradiol receptor (ER) in this process. Lutea l cells isolated from mature porcine corpora lutea were cultured with 25-hy droxycholesterole (25-OH) or pregnenolone (P5) as a substrate. Additionally aminoglutethimide, the inhibitor of P540scc or trilostane the inhibitor of 3 B-HSD was added to basal and stimulated cells. The synergistic action of TCDD with aminoglutethimide in decreasing of progesterone secretion was ob served. In pregnenolone treated cells 1.6 fold decrease of progesterone sec retion was observed that in both TCDD alone and together with trilostane tr eated cells. In the second part of experiments to show the involvement of A hR and ER in TCDD action on progesterone secretion alpha -naphtophlavone, t he AhR blockers and 4-hydroxytamoxifen (4-OH-TMX), the inhibitor of ER were used. alpha -naphtophlavone, the inhibitory effect of TCDD while 4-OH-TMX had no effect on TCDD-treated cells. These experiments suggest TCDD decreas ed progesterone secretion by luteal cells by reduction of the activity of m itochondrial enzymes, which converts cholesterol into pregnenolone. Moreove r points to AhR dependent but not ER-dependent mechanisms in TCDD action in luteal cells.