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Department of Biosciences at Novum (M.O., H.G., K.D.-W., J.-A.G.), Karolinska Institutet, Huddinge SE-14157, Sweden; Division of Endocrinology (C.O.), Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg SE-41345, Sweden; and Department of Molecular Behavioral Biology (N.E., Y.U.), Osaka Bioscience Institute, Osaka 565-0874, Japan
Address all correspondence and requests for reprints to: Dr. Michio Otsuki, Department of Biosciences at Novum, Karolinska Institutet Huddinge SE-14157, Sweden. E-mail michio.otsuki{at}biosci.ki.se.
Estrogens have important physiological roles in the cardiovascular system. We use DNA microarray technology to study the molecular mechanism of estrogen action in the heart and to identify novel estrogen-regulated genes. In this investigation we identify genes that are regulated by chronic estrogen treatment of mouse heart. We present our detailed characterization of one of these genes, lipocalin-type prostaglandin D synthase (L-PGDS). Northern and Western blot analysis revealed that L-PGDS was induced both by acute and chronic estrogen treatment. Northern blot analysis, using estrogen receptor (ER)-disrupted mice, suggests that L-PGDS is specifically induced by ERß in vivo. In further support of ERß-selective regulation, we identify a functional estrogen-responsive element in the L-PGDS promoter, the activity of which is up-regulated by ERß, but not by ER
. We demonstrate that a one-nucleotide change (A to C) in the L-PGDS estrogen-responsive element affects receptor selectivity.
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