title: Effects of genistein, resveratrol, and quercetin on steroidogenesis and proliferation of MA-10 mouse Leydig tumor cells.
abstract: This study was performed to compare the effects of three well-known phytoestrogens such as genistein, resveratrol, and quercetin on steroidogenesis in MA-10 mouse tumor Leydig cells. Addition of genistein or resveratrol to MA-10 cells resulted in decreases in the cAMP-stimulated progesterone secretion, but quercetin had an opposite response. Steroidogenic acute regulatory (StAR) mRNA expression and StAR promoter activity in transiently transfected MA-10 cells were significantly reduced by genistein or resveratrol, but increased by quercetin. Genistein was found to inhibit MA-10 cell proliferation, while resveratrol and quercetin had no effect. Quercetin-induced increase in cAMP-stimulated progesterone secretion was reversed by ICI 182,780, an estrogen receptor (ER) antagonist. However, ICI 182,780 had no effect on cAMP plus quercetin-stimulated StAR promoter activity. To examine whether non-ER factors are associated with quercetin-stimulated progesterone production, we treated MA-10 cells with EGTA to deprive them of extracellular Ca(2+). We found that EGTA inhibited quercetin-plus cAMP-stimulated progesterone secretion and StAR promoter activity. Blocking of Ca(2+) influx through L- or T-type voltage-gated Ca(2+) channels with verapamil or mibefradil respectively, attenuated quercetin-stimulated progesterone secretion, while they had no effect on quercetin-plus cAMP-stimulated StAR promoter activity. Blocking of intracellular Ca(2+) efflux by sodium orthovanadate, a Ca(2+)-pump inhibitor, blocked quercetin- plus cAMP-stimulated progesterone secretion and StAR promoter activity in MA-10 cells. Finally, EGTA or vanadate reduced quercetin and cAMP-increased in StAR mRNA expression in MA-10 cells, while ICI 182,780 had no effect. Taken together, these results indicate that phytoestrogens have differential effects on steroidogenesis in MA-10 cells.
authors.affiliation: Medical and Research Services, WJB Dorn Veterans Medical Center, Columbia, South Carolina 29201, USA.
authors.forename: Yu-Chyu
authors.initials: YC
authors.lastname: Chen
authors.forename: Madan L
authors.initials: ML
authors.lastname: Nagpal
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Stocco
authors.forename: Tu
authors.initials: T
authors.lastname: Lin
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D000077267:Fulvestrant; D019833:Genistein / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020748:Mibefradil / Q000494:pharmacology; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D048789:Phytoestrogens / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D013268:Stimulation, Chemical; D014638:Vanadates / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D002121:Calcium Channel Blockers; D010750:Phosphoproteins; D048789:Phytoestrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013267:Stilbenes; D000098682:Steroidogenic Acute Regulatory Protein; D000077267:Fulvestrant; D020748:Mibefradil; D014638:Vanadates; D011374:Progesterone; D004958:Estradiol; D004533:Egtazic Acid; D011794:Quercetin; D014700:Verapamil; D019833:Genistein; D000242:Cyclic AMP; D000251:Adenosine Triphosphatases; C034688:sodium calcium ATPase; D000077185:Resveratrol