TY - JOUR
T1 - Rosiglitazone and pioglitazone alter aromatase kinetic properties in human granulosa cells
AU - Araki, Takako
AU - Varadinova, Miroslava
AU - Goldman, Michael
AU - Rosenwaks, Zev
AU - Poretsky, Leonid
AU - Seto-Young, Donna
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
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U2 - 10.1155/2011/926438
DO - 10.1155/2011/926438
M3 - Article
C2 - 22220166
AN - SCOPUS:84855614146
SN - 1687-4757
JO - PPAR Research
JF - PPAR Research
M1 - 926438
ER -