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.
Arnold
S F
SF
Department of Environment Health Sciences, Tulane University, School of Public Health and Tropical Medicine, New Orleans, LA, USA.
Collins
B M
BM
Robinson
M K
MK
Guillette
L J
LJ
McLachlan
J A
JA
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