Repression of chick multidrug resistance-associated protein 1 (chMRP1) gene expression by estrogen

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 RNA was isolated from estrogen-treated and estrogen -withdrawn chick oviducts and was subjected to differential display analysi s. Surprisingly, one of the products repressed by estrogen encoded the chic k homolog of the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 Treatment of estrogen-withdrawn chicks with 17 beta -estradiol decreased chMRP1 mRNA le vels to 50% within 30 min and to 70% by 1 h, which is comparable to the lev el observed with chronic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.