Evaluation of Chemicals with Endocrine Modulating Activity in a Yeast-Based Steroid Hormone Receptor Gene Transcription Assay

Evaluation of Chemicals with Endocrine Modulating Activity in a Yeast-Based Steroid Hormone... There is a concern that chemicals in our environment are affecting human health by disrupting normal endocrine function. Much of the concern has focused on chemicals that can interact directly with steroid hormone receptors. We have used a yeast-based assay to assess chemical interactions with the estrogen, androgen, and progesterone receptors. The yeast transformants used in this study contained the human estrogen, androgen, or progesterone receptor along with the appropriate steroid responsive elements upstream of the β-galactosidase reporter gene. Chemicals were added to yeast cultures in doses ranging from 10 −12 to 10 −4 m and following incubation, the yeasts were then lysed and assayed for β-galactosidase activity. Diethylstilbesterol and 17-β estradiol were most active in the estrogen receptor assay, followed by the phytoestrogen, coumestrol. p -Nonylphenol and bisphenol A were approximately 5000- and 15,000-fold less active, respectively, than estradiol. Methoxychlor, DDT and its metabolites, o,p ′-DDD, and o,p ′-DDE ranged in potency from 5 to 24 × 10 6 less potent than estradiol. Testosterone and dihydrotestosterone were most potent in the androgen receptor assay, followed by estradiol and progesterone. p,p ′-DDE was approximately 10 6 -fold less potent than testosterone. None of the industrial chemicals tested interacted with the progesterone receptor. These data demonstrate the utility of using yeast-based receptor assays for detecting chemical interaction with steroid receptors and these assays should serve as a useful component of an in vitro–in vivo strategy to assess the effects of chemicals on endocrine function. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Toxicology and Applied Pharmacology Elsevier

Evaluation of Chemicals with Endocrine Modulating Activity in a Yeast-Based Steroid Hormone Receptor Gene Transcription Assay

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Publisher
Elsevier
Copyright
Copyright © 1997 Academic Press
ISSN
0041-008x
DOI
10.1006/taap.1996.8069
Publisher site
See Article on Publisher Site

Abstract

There is a concern that chemicals in our environment are affecting human health by disrupting normal endocrine function. Much of the concern has focused on chemicals that can interact directly with steroid hormone receptors. We have used a yeast-based assay to assess chemical interactions with the estrogen, androgen, and progesterone receptors. The yeast transformants used in this study contained the human estrogen, androgen, or progesterone receptor along with the appropriate steroid responsive elements upstream of the β-galactosidase reporter gene. Chemicals were added to yeast cultures in doses ranging from 10 −12 to 10 −4 m and following incubation, the yeasts were then lysed and assayed for β-galactosidase activity. Diethylstilbesterol and 17-β estradiol were most active in the estrogen receptor assay, followed by the phytoestrogen, coumestrol. p -Nonylphenol and bisphenol A were approximately 5000- and 15,000-fold less active, respectively, than estradiol. Methoxychlor, DDT and its metabolites, o,p ′-DDD, and o,p ′-DDE ranged in potency from 5 to 24 × 10 6 less potent than estradiol. Testosterone and dihydrotestosterone were most potent in the androgen receptor assay, followed by estradiol and progesterone. p,p ′-DDE was approximately 10 6 -fold less potent than testosterone. None of the industrial chemicals tested interacted with the progesterone receptor. These data demonstrate the utility of using yeast-based receptor assays for detecting chemical interaction with steroid receptors and these assays should serve as a useful component of an in vitro–in vivo strategy to assess the effects of chemicals on endocrine function.

Journal

Toxicology and Applied PharmacologyElsevier

Published: Mar 1, 1997

References

  • Methoxychlor regulates rat uterine estrogen-induced protein
    Cummings, A.M.; Metcalf, J.L.
  • Do environmental estrogens contribute to the decline in male reproductive health?
    Jensen, T.K.; Toppari, J.; Keiding, N.; Skakkebaek, N.E.
  • Alternative splicing of the estrogen receptor primary transcript normally occurs in estrogen receptor positive tissues and cell lines
    Pfeffer, U.; Fecarotta, E.; Arena, G.; Forlani, A.; Vidali, G.
  • Effects of estrogen and nonylphenol on the post-transcriptional regulation of vitellogenin gene expression
    Ren, L.F.; Lewis, S.K.; Lech, J.J.

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