Although a number of genes have been identified whose transcriptional activ
ities are stimulated by estrogen, relatively few have been discovered that
are repressed. In an effort to determine whether estrogen can directly repr
ess gene expression, attempts were made to identify genes that are direct t
argets of the estrogen receptor and whose activities are repressed by it. B
ecause the development and differentiation of the chick oviduct are exquisi
tely dependent upon estrogen, this seemed an appropriate model system for t
esting this hypothesis. RNA was isolated from estrogen-treated and estrogen
-withdrawn chick oviducts and was subjected to differential display analysi
s. Surprisingly, one of the products repressed by estrogen encoded the chic
k homolog of the multidrug resistance-associated protein 1 (MRP1) gene. Fur
ther cloning resulted in a chick MRP1 (chMRP1) cDNA clone that is 72% ident
ical with human MRP1. Translation of the chMRP1 sequence indicates a 77% am
ino acid identity with both the human and mouse MRP1 proteins. Treatment of
estrogen-withdrawn chicks with 17 beta -estradiol decreased chMRP1 mRNA le
vels to 50% within 30 min and to 70% by 1 h, which is comparable to the lev
el observed with chronic repression by estrogen. ChMRP1 mRNA is present in
many other tissues, including the heart, lung, brain, kidney, skeletal musc
le, and intestine, but is undetectable in the liver. This study indicates t
hat in estrogen-responsive tissues such as chick oviduct, the regulation of
chMRP1 gene expression is controlled by estrogen. (C) 2000 Elsevier Scienc
e B.V. All rights reserved.