title: Testosterone up-regulates aquaporin-4 expression in cultured astrocytes.
abstract: Aquaporin-4 (AQP4) is located on astrocyte endfeet that face blood vessels in the brain and in the pia. It is thought to play a crucial role in the development of brain edema. To confirm the notion that sex steroids and dexamethasone influence brain edema through AQP4 regulation, we investigated the effects of 17beta-estradiol, testosterone, and dexamethasone on the expression of AQP4 in cultured astrocytes. Testosterone significantly up-regulated AQP4 at the level of both protein and mRNA. At a concentration of 100 nM, testosterone significantly increased AQP4 protein levels and ameliorated the osmotic fragility of astrocytes from hypoosmotic stress, suggesting that the increased levels of AQP4 facilitated the testosterone function. Moreover, this effect was attenuated by the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate, which can rapidly decrease AQP4 mRNA expression, indicating that the response was specific. These results indicate that AQP4 can alter the osmotic fragility of astrocytes and that testosterone can influence brain edema through AQP4 regulation, whereas 17beta-estradiol and dexamethasone cannot.
authors.affiliation: Department of Anatomy, Ehime University School of Medicine, Shigenobu, Ehime, Japan.
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hata
authors.forename: Kazuko
authors.initials: K
authors.lastname: Toku
authors.forename: Lihua
authors.initials: L
authors.lastname: Yang
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Ma
authors.forename: Nobuji
authors.initials: N
authors.lastname: Maeda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakanaka
authors.forename: Junya
authors.initials: J
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D051401:Aquaporin 4; D020346:Aquaporins / Q000096:biosynthesis* / Q000235:genetics; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D013739:Testosterone / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D020346:Aquaporins; D012333:RNA, Messenger; D013739:Testosterone; D003907:Dexamethasone