Estrogen receptor down-regulation is regulated noncooperatively by estrogen at the transcription level.
We examined noncooperativity of estrogen action by studying the transcription of estrogen receptor (ER) down-regulation in an ER stably transfected cell line (Rat1 + ER). The time-course of the ER transcription rate following 17beta-estradiol (E2) (10 nM) treatment was measured by nuclear run-on assays. ER transcription rates decreased to 40 +/- 3% within 1 h as compared with no treatment and stayed suppressed to 24 h of E2 treatment. The ER transcription rate decrease was noncooperative when measured at 24 h of E2 treatment. This suggested that initial E2 binding to the ER is also a noncooperative process. The Hill coefficients of E2 binding to ER were near unity with an equilibrium dissociation constant of 1-3 nM when measured after a 1 h incubation. These results show that E2 noncooperatively binds ER and down-regulates transcription of ER noncooperatively in intact Ratl + ER cells.
Lee
Y J
YJ
Department of Biochemistry, University of Wisconsin-Madison, 53706-1569, USA.
Gorski
J
J
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects*; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
D004967:Estrogens; D011960:Receptors, Estrogen; D004958:Estradiol