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300 TRANSACTIVATION AND REGULATION OF ESTROGEN RESPONSE ELEMENT BY FUNGAL-DERIVED COMPOUNDS IN TRANSFECTED HUMAN EMBRYONIC KIDNEY 293 CELLS.
  1. A. K. Pandey1,
  2. M. R. Bratton1,
  3. J. A. McLachlan1
  1. 1Environmental Endocrinology Lab, Center for Bioenvironmental Research, Tulane University, New Orleans, LA

Abstract

Endocrine disrupting chemicals (EDCs) are synthetic or natural compounds that possess the ability to mimic or inhibit endogenous hormonal activity. A number of EDCs have been shown to possess estrogenic activity in mammalian systems. The objective of this study was to determine potential estrogenicity of several chemicals derived from fungi (alternariol, AOH; emodin; and hispidin) and the slime mold Dictyostelium (differentiation inducing factor 1 [DIF-1]) with structural similarity to known estrogen-like compounds. Human embryonic kidney (HEK) 293 cells were cotransfected with plasmids containing estrogen response element (ERE)-driven luciferase gene or human estrogen receptor alpha (ERα). Cells were treated with test chemical, 17β-estradiol (E2), and/or estrogen receptor antagonist ICI 182,780. Luciferase activity was determined as a marker for ERE transcriptional activation. The results demonstrated that increasing concentrations of DIF-1 inhibited ERE activity by almost 90% compared with vehicle control. AOH and emodin increased luciferase activity in a dose-dependent manner (up to 20-fold and 11-fold, respectively), and hispidin displayed weaker activation of the ERE (5-fold). ICI abolished the observed up-regulation of luciferase by AOH, emodin, and hispidin. E2 stimulation of AOH- and emodin-treated cells led to a concentration-dependent decrease in luciferase activity of up to 50%, whereas stimulation with E2 caused only a slight decrease in luciferase activity in hispidin-treated cells. The results provide evidence that DIF-1 antagonizes ERα-mediated transcriptional activity. The data further suggest that AOH and emodin, and to a lesser extent hispidin, act as ERα agonists, whereas AOH and emodin may also possess antiestrogenic properties. The findings of these studies implicate that fungi and other microfauna can be important contributors of estrogenic EDCs found in the environment.

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