Bisphenol a disrupts steroidogenesis in human H295R cells

Xiaowei Zhang*, Hong Chang, Steve Wiseman, Yuhe He, Eric Higley, Paul Jones, Chris K C WONG, Abdulaziz Al-Khedhairy, John P. Giesy, Markus Hecker

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

91 Citations (Scopus)

Abstract

There is increasing concern over the risk of environmentally relevant doses of bisphenol A (BPA) on human endocrine systems. Effects of BPA on steroidogenesis and the related molecular mechanisms were investigated in H295R human adenocarcinoma cells. This immortal cell line is unique in expressing all the enzymes of the steroidogenic pathways. The effects of BPA on steroidogenesis, 17β-estradiol (E2) metabolism, and aromatase activity were examined in H295R cells exposed to BPA from 3.0 × 10-1 to 3.0 × 103 ng/ml. Concentrations of BPA in basic cell culture materials were verified. Stable CYP17A-knockdown H295R cells were developed to verify the mechanism of inhibited steroidogenesis by BPA. Background concentrations of BPA in control cell culture media ranged from 0.03 to 0.38 ng/ml. Significantly lesser concentrations of androstenedione, testosterone, cortisol, and cortisone were caused by exposure to 30-3000 ng BPA/ml. In contrast, sconcentrations of estrone (E1) and E2 were significantly greater in BPA-exposed H295R cells. Lesser production of androstenedione and testosterone by H295R cells exposed to BPA was the most sensitive endpoint (no observable effect concentrations < 30 ng BPA/ml). CYP17A knockdown in H295R cells resulted in less production of both 17α hydroxyprogesterone and androstenedione. The results are consistent with the hypothesis that in H295R cells, BPA selectively inhibits 17,20-lyase but not 17α-hydroxylase. The primary mechanism causing increased E2 in the medium was inhibition of E2 metabolism rather than greater aromatase (CYP19) activity. These results suggest thatBPAhas the potential to interfere with cellular steroidogenesis in humans through multiple molecular mechanisms.

Original languageEnglish
Pages (from-to)320-327
Number of pages8
JournalToxicological Sciences
Volume121
Issue number2
DOIs
Publication statusPublished - Jun 2011

Scopus Subject Areas

  • Toxicology

User-Defined Keywords

  • 17,20-lyase
  • Aromatase
  • Cellular uptake
  • CYP17A
  • CYP19
  • Endocrine disruption
  • Estradiol
  • Metabolism

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