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.
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.
Ohtsuki
Sumio
S
Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Sendai, Japan.
Tomi
Masatoshi
M
Hata
Toshio
T
Nagai
Yoko
Y
Hori
Satoko
S
Mori
Shinobu
S
Hosoya
Ken-Ichi
K
Terasaki
Tetsuya
T
D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D001813:Blood-Retinal Barrier / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000098:blood supply*; D002460:Cell Line; D013196:Dihydrotestosterone / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D015870:Gene Expression / Q000235:genetics*; D005786:Gene Expression Regulation; D008297:Male; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D012727:Sex Characteristics
D029362:Organic Anion Transporters, Sodium-Independent; D012333:RNA, Messenger; D011944:Receptors, Androgen; C114338:organic anion transport protein 3; D013196:Dihydrotestosterone; D005485:Flutamide