| 1. |
- Lindberg, Marie K, 1975, et al.
(författare)
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Estrogen receptor (ER)-beta reduces ERalpha-regulated gene transcription, supporting a "ying yang" relationship between ERalpha and ERbeta in mice.
- 2003
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Ingår i: Molecular endocrinology (Baltimore, Md.). - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 17:2, s. 203-8
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen is of importance for the regulation of adult bone metabolism. The aim of the present study was to determine the role of estrogen receptor-beta (ERbeta) in vivo on global estrogen-regulated transcriptional activity in bone. The effect of estrogen in bone of ovariectomized mice was determined using microarray analysis including 9400 genes. Most of the genes (95% = 240 genes) that were increased by estrogen in wild-type (WT) mice were also increased by estrogen in ERbeta-inactivated mice. Interestingly, the average stimulatory effect of estrogen on the mRNA levels of these genes was 85% higher in ERbeta-inactivated than in WT mice, demonstrating that ERbeta reduces estrogen receptor-alpha (ERalpha)-regulated gene transcription in bone. The average stimulatory effect of estrogen on estrogen-regulated bone genes in ERalpha-inactivated mice was intermediate between that seen in WT and ERalphabeta double-inactivated mice. Thus, ERbeta inhibits ERalpha-mediated gene transcription in the presence of ERalpha, whereas, in the absence of ERalpha, it can partially replace ERalpha. In conclusion, our in vivo data indicate that an important physiological role of ERbeta is to modulate ERalpha-mediated gene transcription supporting a "Ying Yang" relationship between ERalpha and ERbeta in mice.
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| 2. |
- Otsuki, Michio, et al.
(författare)
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Specific regulation of lipocalin-type prostaglandin D synthase in mouse heart by estrogen receptor beta.
- 2003
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Ingår i: Molecular endocrinology (Baltimore, Md.). - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 17:9, s. 1844-55
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Tidskriftsartikel (refereegranskat)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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