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 progesterone secretion by luteal cells under the influence of 2,3,7,8-tetrachlorodibezo-p-dioxin (TCDD) is due to influence on specific enzymatic steps in the biosynthetic pathway of steroidogenesis and secondly, involvement of aryl hydrocarbon receptor (AhR) or estradiol receptor (ER) in this process. Luteal cells isolated from mature porcine corpora lutea were cultured with 25-hydroxycholesterole (25-OH) or pregnenolone (P5) as a substrate. Additionally aminoglutethimide, the inhibitor of P540scc or trilostane the inhibitor of 3 beta-HSD was added to basal and stimulated cells. The synergistic action of TCDD with aminoglutethimide in decreasing of progesterone secretion was observed. In pregnenolone treated cells 1.6 fold decrease of progesterone secretion was observed that in both TCDD alone and together with trilostane treated cells. In the second part of experiments to show the involvement of AhR and ER in TCDD action on progesterone secretion alpha- naphtophlavone, the 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 decreased progesterone secretion by luteal cells by reduction of the activity of mitochondrial enzymes, which converts cholesterol into pregnenolone. Moreover points to AhR dependent but not ER-dependent mechanisms in TCDD action in luteal cells.
Gregoraszczuk
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Department of Physiology, Jagiellonian University, Kraków, Poland. greg@zuk.iz.uj.edu.pl
Zabielny
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Ochwat
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D000818:Animals; D004785:Environmental Pollutants / Q000494:pharmacology*; D005260:Female; D008184:Luteal Cells / Q000187:drug effects* / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011374:Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013552:Swine
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011374:Progesterone