Rosiglitazone and pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase

D. Seto-Young, D. Avtanski, G. Parikh, P. Suwandhi, M. Strizhevsky, T. Araki, Z. Rosenwaks, L. Poretsky

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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 17-hydroxysteroid-dehydrogenase (17-HSD) inhibitor. Estrogen concentrations in the conditioned medium, aromatase mRNA and protein expression in the cells and androgen substrate binding to aromatase were measured. With androstenedione as substrate, rosiglitazone or pioglitazone inhibited estrone production by up to 22% (p<0.012) while type 1 17-HSD inhibitor enhanced this effect of rosiglitazone or pioglitazone by 37% (p<0.001) and by 67% (p<0.001), respectively. With testosterone as substrate, rosiglitazone or pioglitazone inhibited estradiol production by 32% (p<0.001). With 3H- testosterone as substrate, rosiglitazone or pioglitazone inhibited the 3H-tritiated water release by the cultured cells by 45% and 35%, respectively, thus directly demonstrating inhibition of aromatase. Rosiglitazone or pioglitazone, however, had no significant effect on aromatase mRNA or protein expression. Rosiglitazone or pioglitazone inhibited 125I- androstenedione and 125I-testosterone binding to aromatase by 38% (p<0.001). It was concluded that rosiglitazone or pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase.

Original languageEnglish (US)
Pages (from-to)250-256
Number of pages7
JournalHormone and Metabolic Research
Volume43
Issue number4
DOIs
StatePublished - Feb 16 2011

Keywords

  • PPAR-
  • aromatase
  • estrogens
  • insulin sensitivity
  • polycystic ovary syndrome
  • thiazolidinediones

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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  • Cite this

    Seto-Young, D., Avtanski, D., Parikh, G., Suwandhi, P., Strizhevsky, M., Araki, T., Rosenwaks, Z., & Poretsky, L. (2011). Rosiglitazone and pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase. Hormone and Metabolic Research, 43(4), 250-256. https://doi.org/10.1055/s-0030-1270525