Rosiglitazone and Pioglitazone Alter Aromatase Kinetic Properties in Human Granulosa Cells
نویسندگان
چکیده
We have previously reported that, in human granulosa cells, thiazolidinediones rosiglitazone and pioglitazone inhibit estrogen synthesis by interfering with androgen binding to aromatase, without an effect on aromatase mRNA or protein expression. In the current paper, we explore the effects of rosiglitazone and pioglitazone on the aromatase enzyme kinetic properties in human granulosa cells. The cells were incubated with various concentrations of testosterone or androstenedione, with or without rosiglitazone or pioglitazone. Estradiol and estrone concentrations in the conditioned tissue culture medium were measured by radioimmunoassay or immunosorbent assay. When testosterone was used as substrate, rosiglitazone or pioglitazone inhibited the V(max) by 35% (P < 0.001) and 24% (P < 0.001), respectively. When androstenedione was used as substrate, both rosiglitazone or pioglitazone inhibited V(max) by 13% (P < 0.007). We conclude that rosiglitazone or pioglitazone has no effect on K(m) but inhibits V(max) of aromatase in human granulosa cells, therefore, acting as noncompetitive inhibitors.
منابع مشابه
Rosiglitazone and pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase.
The effects of rosiglitazone or pioglitazone (thiazolidinediones, TZDs) on estrogen production and aromatase activity in human ovarian cells were examined. Human granulosa cells were incubated in the tissue culture medium supplemented with androstenedione or testosterone, with or without insulin, TZDs, or type 1 17β-hydroxysteroid-dehydrogenase (17β-HSD) inhibitor. Estrogen concentrations in th...
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عنوان ژورنال:
دوره 2011 شماره
صفحات -
تاریخ انتشار 2011