DIFFERENTIAL INTERACTION OF NATURAL AND SYNTHETIC ESTROGENS WITH EXTRACELLULAR BINDING-PROTEINS IN A YEAST ESTROGEN SCREEN

We have used the yeast estrogen screen (YES) consisting of the human e strogen receptor and a reporter containing two estrogen response eleme nts linked to the lacZ gene to evaluate the interaction between ovaria n, phyto-, and synthetic estrogens with extracellular binding proteins . YES was incubated,vith charcoal-stripped human serum, human sex horm one-binding globulin, or human alpha-feroprotein in the presence of co ncentrations of various estrogens that induced a 100% estrogenic respo nse, as measured by beta-galactosidase activity. The activity of estra diol and coumestrol, a phyroestrogen, was reduced 75% with physiologic al levels of serum, sex hormone-binding globulin, or alpha-fetoprotein . The beta-galactosidase activity of genistein, another phytoestrogen, also decreased with extracellular proteins but to a lower extent than estradiol. In contrast, the activity of the synthetic estrogens dieth ylstilbestrol, kepone, and p,p'-DDD was only minimally reduced with ex tracellular proteins. These results indicate a potential fundamental d ifference in the interaction of estrogens from diverse sources with ex tracellular binding proteins. This suggests that the capacity for vari ous estrogens to induce estrogen-associated responses is in part regul ated by their affinity for extracellular binding proteins. (C) 1996 by Elsevier Science Inc.