Specific regulation of lipocalin-type prostaglandin D synthase in mouse heart by estrogen receptor beta |
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Authors: | Otsuki Michio Gao Hui Dahlman-Wright Karin Ohlsson Claes Eguchi Naomi Urade Yoshihiro Gustafsson Jan-Ake |
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Institution: | Department of Biosciences at Novum, Karolinska Institutet Huddinge SE-14157, Sweden. michio.otsuki@biosci.ki.se. |
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Abstract: | 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 ERbeta in vivo. In further support of ERbeta-selective regulation, we identify a functional estrogen-responsive element in the L-PGDS promoter, the activity of which is up-regulated by ERbeta, but not by ERalpha. We demonstrate that a one-nucleotide change (A to C) in the L-PGDS estrogen-responsive element affects receptor selectivity. |
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