Specific regulation of lipocalin-type prostaglandin D synthase in mouse heart by estrogen receptor beta.
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.
Otsuki
Michio
M
Department of Biosciences at Novum, Karolinska Institutet Huddinge SE-14157, Sweden. michio.otsuki@biosci.ki.se.
Gao
Hui
H
Dahlman-Wright
Karin
K
Ohlsson
Claes
C
Eguchi
Naomi
N
Urade
Yoshihiro
Y
Gustafsson
Jan-Ake
JA
D000818:Animals; D004247:DNA / Q000378:metabolism; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D019746:Intramolecular Oxidoreductases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D054834:Lipocalins; D051379:Mice; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000378:metabolism*
D047629:Estrogen Receptor beta; D004967:Estrogens; D054834:Lipocalins; D011960:Receptors, Estrogen; D004247:DNA; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase