EVALUATION OF CHEMICALS WITH ENDOCRINE MODULATING ACTIVITY IN A YEAST-BASED STEROID-HORMONE RECEPTOR GENE-TRANSCRIPTION ASSAY

There is a concern that chemicals in our environment are affecting hum an health by disrupting normal endocrine function. Much of the concern has focused on chemicals that can interact directly with steroid horm one receptors. We have used a yeast-based assay to assess chemical int eractions 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 P-galactosidase reporter gene. Che micals were added to yeast cultures in doses ranging from 10(-12) to 1 0(-4) M and following incubation, the yeasts were then lysed and assay ed for beta-galactosidase activity. Diethylstilbesterol and 17-beta es tradiol were most active in the estrogen receptor assay, followed by t he phytoestrogen, coumestrol. p-Nonylphenol and bisphenol A were appro ximately 5000- and 15,000-fold less active, respectively, than estradi ol. Methoxychlor, DDT and its metabolites, o,p'-DDD, and o,p'-DDE rang ed in potency from 5 to 24 x 10(6) less potent than estradiol. Testost erone and dihydrotestosterone were most potent in the androgen recepto r assay, followed by estradiol and progesterone. p,p'-DDE was approxim ately 10(6)-fold less potent than testosterone. None of the industrial chemicals tested interacted with the progesterone receptor. These dat a demonstrate the utility of using yeast-based receptor assays for det ecting chemical interaction with steroid receptors and these assays sh ould serve as a useful component of an in vitro-in vivo strategy to as sess the effects of chemicals on endocrine function. (C) 1997 Academic Press.