Differential interaction of natural and synthetic estrogens with extracellular binding proteins in a yeast estrogen screen.
We have used the yeast estrogen (YES) consisting of the human estrogen receptor and a reporter containing two estrogen response elements linked to the lacZ gene to evaluate the interaction between ovarian, phyto-, and synthetic estrogens with extracellular binding proteins. YES was incubated with charcoal-stripped human serum, human sex hormone-binding globulin, or human alpha-fetoprotein in the presence of concentrations of various estrogens that induced a 100% estrogenic response, as measured by beta-galactosidase activity. The activity of estradiol and coumestrol, a phytoestrogen, was reduced 75% with physiological 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 diethylstilbestrol, kepone, and p,'p-DDD was only minimally reduced with extracellular proteins. These results indicate a potential fundamental difference in the interaction of estrogens from diverse sources with extracellular binding proteins. This suggests that the capacity for various estrogens to induce estrogen-associated responses is in part regulated by their affinity for extracellular bindings proteins.
Department of Environment Health Sciences, Tulane University, School of Public Health and Tropical Medicine, New Orleans, LA, USA.
S F
SF
Arnold
B M
BM
Collins
M K
MK
Robinson
L J
LJ
Guillette
J A
JA
McLachlan
D000328:Adult; D001798:Blood Proteins / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
D001798:Blood Proteins; D004967:Estrogens; D012738:Sex Hormone-Binding Globulin; D000509:alpha-Fetoproteins