Binding and biologic activity of diethylstilbestrol in the hamster: influence of a serum component on estrogen receptor binding and estrogenic activity.
The purpose of this study was to compare the biological activity and estrogen receptor (Re) binding affinity of diethylstilbestrol (DES) and estradiol (E2). Uterine weight response and cytosolic progesterone receptor (Rp) induction were equivalent following daily (3 days) injections of DES or E2 to ovariectomized animals. The biological equivalence of DES and E2 was not reflected by competition assays done with either uterine cytosolic or nuclear Re: the relative binding affinity (RBA) of DES to cytosolic Re was 46 +/- 5.3 and to nuclear Re was 380 +/- 42 compared to E2 (100). The RBAs of estrone, estriol and enclomiphene with cytosolic or nuclear Re were not significantly different. Further studies showed that this discrepancy in RBA of DES between cytosolic and nuclear Re could not be attributed to salt concentration but could be mimicked by addition of serum to nuclear Re preparations. The RBA of DES done with ammonium sulfate precipitated cytosolic Re approached that observed for nuclear Re. Gel filtration chromatography (Sephacryl S-300) of serum bound tritiated DES was shown to coelute with bovine serum albumin. These results suggest that a serum component (tentatively identified as albumin) can bind DES and cause a decrease in in vitro binding affinity and a reduction in biological activity in vivo.
D000645:Ammonium Sulfate; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D011232:Chemical Precipitation; D002996:Clomiphene / Q000031:analogs & derivatives / Q000378:metabolism; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D004054:Diethylstilbestrol / Q000378:metabolism* / Q000494:pharmacology; D064695:Enclomiphene; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D004964:Estriol / Q000378:metabolism; D004970:Estrone / Q000378:metabolism; D005260:Female; D008647:Mesocricetus; D009929:Organ Size / Q000187:drug effects; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism / Q000494:pharmacology*; D014599:Uterus / Q000033:anatomy & histology
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D012709:Serum Albumin; D002996:Clomiphene; D004970:Estrone; D004958:Estradiol; D004054:Diethylstilbestrol; D004964:Estriol; D064695:Enclomiphene; D000645:Ammonium Sulfate