【摘 要】
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Context and Objective:Thiazolidinediones (TZDs) inhibit estrogen production in ovarian cells.We explored whether TZDs affect aromatase activity.Materials &
【机 构】
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Endocrinology & Metabolism Laboratory USA
【出 处】
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中国上海第七届国际新药发明科技年会
论文部分内容阅读
Context and Objective:Thiazolidinediones (TZDs) inhibit estrogen production in ovarian cells.We explored whether TZDs affect aromatase activity.Materials & Methods:Human granulosa cells were incubated in culture medium supplemented with 3 μ M of androstenedione or testosterone,with or without insulin,TZDs (25-50 μ M),type 1 aromatase inhibitor (AI) (100-200 nM) or 17-hydroxysteroid-dehydrogenase (17-HSD) inhibitor type 1 or type 2 (1-5 μM).Estrogen concentration in medium,aromatase mRNA and protein expression,and substrate binding to aromatase were measured.Results:With androstenedione as substrate,estrone production was inhibited by TZDs by 22% (p<0.012).AI abolished inhibitory effect of TZDs on estrogen production,while Type 1 17-HSD inhibitor enhanced rosiglitazone or pioglitazone inhibition of estrone production by 37% (p<0.001) and 67% (p<0.001),respectively.With testosterone as substrate,estradiol production was inhibited by TZDs by 34% (p<0.001).AI reduced inhibitory effect of TZDs on estradiol production by 62% (p<0.001),while Type 2 17-HSD inhibitor (which inhibits both type 2 17-HSD and aromatase activity) abolished inhibitory effects of TZDs on estradiol production.
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