Dominant expression of androgen receptors and their functional regulation of organic anion transporter 3 in rat brain capillary endothelial cells; Comparison of gene expression between the blood–brain and ‐retinal barriers
Dominant expression of androgen receptors and their functional regulation of organic anion transporter 3 in rat brain capillary endothelial cells; Comparison of gene expression between the blood–brain and ‐retinal barriers
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DOI：
10.1002/jcp.20352
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发表时间：
2005-09
影响因子：
5.6
通讯作者：
S. Ohtsuki;M. Tomi;T. Hata;Y. Nagai;Satoko Hori;Shinobu Mori;K. Hosoya;T. Terasaki
中科院分区：
文献类型：
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作者：
S. Ohtsuki;M. Tomi;T. Hata;Y. Nagai;Satoko Hori;Shinobu Mori;K. Hosoya;T. Terasaki
脑和视网膜毛细血管内皮细胞（分别为BCEC和RCEC）表现出屏障结构和功能。比较这些细胞中的基因表达可以阐明每个屏障的选择性功能。本研究的目的是鉴定血脑屏障（BBB）上选择性表达的基因，并阐明选择性基因雄激素受体（AR）的功能。通过使用条件永生化大鼠BCEC和RCEC（分别为TR-BBB和TR-iBRB）的差异显示来比较基因表达。共鉴定出12个基因片段为TR-BBB细胞中优势表达的选择性基因。TR-BBB细胞中选择性最强的片段与人和小鼠AR的3′-UTR具有最高的同源性。在TR‐BBB细胞和脑毛细血管丰富部分中检测到大鼠AR mRNA，但在TR‐iBRB细胞中未检测到。TR-BBB细胞中有机阴离子转运蛋白3（OAT 3）mRNA的表达通过用双氢睾酮（DHT）（一种AR配体）处理诱导，并且该诱导被氟替卡松抑制。此外，DT-BBB细胞对苄青霉素的摄取也被DHT处理诱导。相反，OAT 3 mRNA在TR‐iBRB细胞中的表达不受DHT处理的影响。苄青霉素的脑-血外排率不受性别影响。这些结果表明，AR参与了BBB中OAT 3的功能调节，但不参与内部血视网膜屏障（iBRB）的功能调节，并且这种调节不受性别影响。BBB功能将通过AR受到脑和/或血浆中雄激素水平的影响。© 2005 Wiley利斯公司
Brain and retinal capillary endothelial cells (BCECs and RCECs, respectively) exhibit a barrier structure and function. Comparison of gene expression in these cells could clarify the selective function of each barrier. The purpose of this study was to identify the genes selectively expressed at the blood–brain barrier (BBB) and to clarify the function of the selective gene, androgen receptor (AR). Gene expression was compared by a differential display using conditionally immortalized rat BCECs and RCECs (TR‐BBB and TR‐iBRB, respectively). A total of 12 gene fragments were identified as the selective genes dominantly expressed in TR‐BBB cells. The most selective fragment in TR‐BBB cells had the highest homology with the 3′‐UTR of human and mouse AR. Rat AR mRNA was detected in TR‐BBB cells and the brain capillary rich fraction, but not in TR‐iBRB cells. Expression of organic anion transporter 3 (OAT3) mRNA in TR‐BBB cells was induced by treatment with dihydrotestosterone (DHT), an AR ligand, and this induction was suppressed by flutamide. Moreover, uptake of benzylpenicillin by TR‐BBB cells was also induced by DHT treatment. In contrast, OAT3 mRNA expression in TR‐iBRB cells was not affected by DHT treatment. The brain‐to‐blood efflux rate of benzylpenicillin was not affected by gender. These results suggest that AR is involved in the functional regulation of OAT3 at the BBB, but not at the inner blood‐retinal barrier (iBRB), and this regulation is not affected by gender. The BBB function will be affected by the androgen levels in the brain and/or plasma via AR. © 2005 Wiley‐Liss, Inc.