Rosiglitazone and Pioglitazone Alter Aromatase Kinetic Properties in Human Granulosa Cells
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 rosig...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2011/926438 |
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| author | Takako Araki Miroslava Varadinova Michael Goldman Zev Rosenwaks Leonid Poretsky Donna Seto-Young |
| author_facet | Takako Araki Miroslava Varadinova Michael Goldman Zev Rosenwaks Leonid Poretsky Donna Seto-Young |
| author_sort | Takako Araki |
| collection | DOAJ |
| description | 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 Vmax by 35% (P<0.001) and 24% (P<0.001), respectively. When androstenedione was used as substrate, both rosiglitazone or pioglitazone inhibited Vmax by 13% (P<0.007). We conclude that rosiglitazone or pioglitazone has no effect on Km but inhibits Vmax of aromatase in human granulosa cells, therefore, acting as noncompetitive inhibitors. |
| format | Article |
| id | doaj-art-fcda5c4967524f399c1df343b08d6097 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-fcda5c4967524f399c1df343b08d60972025-02-03T01:20:28ZengWileyPPAR Research1687-47571687-47652011-01-01201110.1155/2011/926438926438Rosiglitazone and Pioglitazone Alter Aromatase Kinetic Properties in Human Granulosa CellsTakako Araki0Miroslava Varadinova1Michael Goldman2Zev Rosenwaks3Leonid Poretsky4Donna Seto-Young5Gerald J. Friedman Diabetes Institute and the Division of Endocrinology, Department of Medicine, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, NY 10003, USAGerald J. Friedman Diabetes Institute and the Division of Endocrinology, Department of Medicine, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, NY 10003, USAGerald J. Friedman Diabetes Institute and the Division of Endocrinology, Department of Medicine, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, NY 10003, USARonald O. Perelman and Cohen Center for Reproductive Medicine and Infertility, Weill Medical College of Cornell University, New York, NY 10021, USAGerald J. Friedman Diabetes Institute and the Division of Endocrinology, Department of Medicine, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, NY 10003, USAGerald J. Friedman Diabetes Institute and the Division of Endocrinology, Department of Medicine, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, NY 10003, USAWe 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 Vmax by 35% (P<0.001) and 24% (P<0.001), respectively. When androstenedione was used as substrate, both rosiglitazone or pioglitazone inhibited Vmax by 13% (P<0.007). We conclude that rosiglitazone or pioglitazone has no effect on Km but inhibits Vmax of aromatase in human granulosa cells, therefore, acting as noncompetitive inhibitors.http://dx.doi.org/10.1155/2011/926438 |
| spellingShingle | Takako Araki Miroslava Varadinova Michael Goldman Zev Rosenwaks Leonid Poretsky Donna Seto-Young Rosiglitazone and Pioglitazone Alter Aromatase Kinetic Properties in Human Granulosa Cells PPAR Research |
| title | Rosiglitazone and Pioglitazone Alter Aromatase Kinetic Properties in Human Granulosa Cells |
| title_full | Rosiglitazone and Pioglitazone Alter Aromatase Kinetic Properties in Human Granulosa Cells |
| title_fullStr | Rosiglitazone and Pioglitazone Alter Aromatase Kinetic Properties in Human Granulosa Cells |
| title_full_unstemmed | Rosiglitazone and Pioglitazone Alter Aromatase Kinetic Properties in Human Granulosa Cells |
| title_short | Rosiglitazone and Pioglitazone Alter Aromatase Kinetic Properties in Human Granulosa Cells |
| title_sort | rosiglitazone and pioglitazone alter aromatase kinetic properties in human granulosa cells |
| url | http://dx.doi.org/10.1155/2011/926438 |
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