The 2,2',4,4'-tetrabromodiphenyl ether hydroxylated metabolites 5-OH-BDE-47 and 6-OH-BDE-47 stimulate estradiol secretion in the ovary by activating aromatase expression

Toxicology. 2013 Mar 8:305:65-70. doi: 10.1016/j.tox.2012.10.021. Epub 2012 Nov 9.

Abstract

The aim of the present study was to assess the effect of two hydroxylated BDE-47 metabolites, 5-OH-BDE-47 and 6-OH-BDE-47, on steroidogenesis in the ovary. Both metabolites failed to affect the production of androstenedione and testosterone but increased the secretion of estradiol at all concentrations tested. The increased secretion of estradiol was due to the stimulation of aromatase gene and protein expression. Direct assessment of aromatase activity by dibenzylfluorescein assay and indirect assessment of aromatase activity by measurement of the conversion of testosterone to estradiol confirmed that 5-OH-BDE-47 and 6-OH-BDE-47 stimulate aromatase activity. The aromatase inhibitor CGS 16949A abolished this stimulatory activity and reduced estradiol levels in the control and treatment groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Aromatase / biosynthesis
  • Aromatase / genetics
  • Aromatase / metabolism*
  • Blotting, Western
  • Cells, Cultured
  • Endocrine Disruptors / pharmacology*
  • Enzyme Activation / drug effects
  • Estradiol / metabolism*
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism
  • Halogenated Diphenyl Ethers
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / metabolism
  • Ovary / drug effects
  • Ovary / metabolism*
  • Polybrominated Biphenyls / toxicity*
  • Real-Time Polymerase Chain Reaction
  • Steroids / biosynthesis
  • Swine
  • Testosterone / metabolism
  • Theca Cells / drug effects
  • Theca Cells / metabolism

Substances

  • 5-OH-BDE-47
  • 6-OH-BDE-47
  • Actins
  • Endocrine Disruptors
  • Halogenated Diphenyl Ethers
  • Polybrominated Biphenyls
  • Steroids
  • 2,2',4,4'-tetrabromodiphenyl ether
  • Testosterone
  • Estradiol
  • Aromatase