Bimodal nuclear estrogen receptor binding: synchrony in athymic mouse uterus and human breast tumor xenografts.
Human MCF-7 tumors were transplanted into ovariectomized female athymic nude mice supplemented with estradiol pellets. Ten days after hormone pellet removal, the animals were treated with 10 micrograms/kg estradiol, and the nuclear estrogen receptor (ERn) profile was assessed by the exchange assay. The pattern in the tumors was qualitatively similar to that in the uterus. A bimodal pattern of ERn was seen, with peaks at 1 and 8 h. Further biochemical analysis of uterine samples showed that both peaks were comprised of similar levels of salt-resistant ERn forms. Scatchard plot analysis of estradiol binding demonstrated high affinity receptors (Kd = 0.73-0.86 nM) as components of both peaks. In the ovariectomized adult rat there was also a bimodal pattern of ERn 1 and 13-14 h after the injection of 20 micrograms/kg estradiol. Direct hormone stimulation of the uterus was achieved with intraluminal (IL) injection of estradiol. IL injections of estradiol (100-800 pg/horn) stimulated uterine DNA synthesis compared to IL saline injections in the contralateral horn. IL injection of 200 pg/horn estradiol resulted in a bimodal pattern of ERn at 3 and 9 h. These data indicate that a bimodal pattern of ERn is present in estrogen target tissues exhibiting a growth response.
Beckman
W C
WC
Department of Surgery, University of North Carolina Medical School, Chapel Hill 27514.
Hudspeth
D A
DA
Golding
T
T
Hubbert
L
L
Akkerman
J
J
Korach
K S
KS
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010052:Ovariectomy; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D011960:Receptors, Estrogen; D004958:Estradiol