Liver receptor homologue-1 (LRH-1) activates the promoter of brain aromatase (cyp19a2) in a Teleost fish, the Medaka, Oryzias latipes
Liver receptor homologue-1 (LRH-1) activates the promoter of brain aromatase (cyp19a2) in a Teleost fish, the Medaka, Oryzias latipes
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DOI：
10.1002/mrd.20497
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发表时间：
2007-09-01
影响因子：
2.5
通讯作者：
Nagahama, Yoshitaka
中科院分区：
文献类型：
--
作者：
Ohmuro-Matsuyama, Yuki;Okubo, Kataaki;Nagahama, Yoshitaka
青鳉，Oryzias latipes，像其他鱼类一样，有两种不同的芳香化酶基因，卵巢（cyp 19 a1）和大脑（cyp 19 a2）形式。我们以前报道过，Ad 4 BP/SF-1，NR 5A亚家族的成员，在青鳉卵黄发生过程中卵巢卵泡cyp 19 a1表达的调节中起着重要作用。在本研究中，我们调查是否肝受体同源物-1（LRH-1），另一个NR 5A亚家族成员，参与调节CYP 19 A2在青鳉脑中的表达。原位杂交分析表明，LRH-1的表达在下丘脑，在那里它与芳香化酶（cyp 19 a2）共定位。然后，我们通过瞬时转染试验表明，LRH-1能够增加cyp 19 a2报告基因在各种哺乳动物细胞系中的表达，并且cyp 19 a2启动子内假定的LRH-1结合位点的突变消除了这种效应。总之，这些发现表明，LRH-1在调节青鳉脑中cyp 19 a2的表达中起作用。这是第一次在体外证明LRH-1在脊椎动物脑中激活脑芳香化酶。
The medaka, Oryzias latipes, like other fish, have two distinct aromatase genes, the ovarian (cyp19a1) and brain (cyp19a2) forms. We previously reported that Ad4BP/SF-1, a member of the NR5A subfamily, plays an important role in the regulation of cyp19a1 expression in medaka ovarian follicles during vitellogenesis. In the present study, we investigated whether liver receptor homologue-1 (LRH-1), another NR5A subfamily member, is involved in the regulation of cyp19a2 expression in the medaka brain. In situ hybridization analysis revealed that LRH-1 was expressed in the hypothalamus, where it colocalized with aromatase (cyp19a2). We then showed by transient transfection assays that LRH-1 was able to increase expression of a cyp19a2 reporter gene in various mammalian cell lines, and that mutation of a putative LRH-1 binding site within the cyp19a2 promoter abolished this effect. Taken together, these findings suggest that LRH-1 plays a role in regulating cyp19a2 expression in the medaka brain. This is the first to demonstrate in vitro the activation of brain aromatase by LRH-1 in the vertebrate brain.