O,P'-DDT AND ITS METABOLITES INHIBIT PROGESTERONE-DEPENDENT RESPONSESIN YEAST AND HUMAN-CELLS

Using a combination of in vitro assays we have evaluated whether DDT m etabolites can interact with the progesterone receptor pathway in yeas t expressing human progesterone receptor (hPR) and in T47D human breas t cancer cells which express endogenous hPR. In transactivation assays using both yeast and T47D cells, o,p'-DDT and the metabolites p,p'-DD T, o,p'-DDD, p,p'-DDD, o,p'-DDE, p,p'-DDE, p,p'-DDA, and DDOH inhibite d progesterone-induced reporter gene activity in a dose-dependent mann er. None of the DDT metabolites functioned as hPR agonists. Whole cell competition binding assays using T47D cells indicated that the inhibi tory effects of DDT metabolites on progesterone-dependent activities m ay occur through both hPR-dependent and hPR-independent pathways. Our results and previous reports of DDT metabolites interacting with estro gen and androgen receptors suggests that this class of environmental c hemicals may interact with numerous hormone receptor signaling pathway s. (C) 1997 Elsevier Science Ireland Ltd.