期刊
JOURNAL OF ENDOCRINOLOGY
卷 232, 期 1, 页码 85-95出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-16-0434
关键词
hypoxic-ischemic encephalopathy; estetrol; ER alpha; ER beta; myelination
资金
- Fonds de la Recherche Scientifique - FNRS (F.R.S. - FNRS, Belgium) [FRSM 3.4557.12, FRSM 3.4526.12, FRSM 3.4567.11, PDR T.0091.14]
- Fonds speciaux de la Recherche (University of Liege, Belgium) [FSRC-12/64, FSRC-12/92, FSRC-14/89, FSRC-14/65, FSRC-14/109, FSRC-14/62]
- Fonds Leon Fredericq (University of Liege, Belgium)
- Direction Generale Operationnelle de l'Economie, de l'Emploi et de la Recherche from the Service Public de Wallonie (SPW, Belgium) [1318051, 1318039, 1318030, 1318071, 1318023]
- Interuniversity Attraction Poles Programme-Belgian Science Policy (Brussels, Belgium) [VII - P7/03]
- Actions de Recherche Concertees (University of Liege, Belgium) [A.R.C. 11/16-02]
Estetrol (E4) has strong antioxidative, neurogenic and angiogenic effects in neural system resulting in the attenuation of neonatal hypoxic ischemic encephalopathy. We aimed to define the role of estrogen receptors in E4-dependent actions in neuronal cell cultures and prove the promyelinating effect of E4. In vitro the antioxidative and cell survival/ proliferating effects of E4 on H20,-induced oxidative stress in primary hippocampal cell cultures were studied using different combinations of specific inhibitors for ER alpha (MPP dihydrochloride), ER beta (PHTTP), GPR3O (G15) and palmytoilation (2-BR). LDH activity and cell survival assays were performed. In vivo the promyelinating role of different concentrations of E4 (1 mg/kg/day, 5 mg/kg/day, 10 mg/kg/day, 50 mg/kg/day) was investigated using the hypoxic ischemic brain damage model in the 7-day-old immature rats before/after the induction of hypoxic ischemic insult. Myelin basic protein (MBP) immunostaining was performed on brain coronal sections. Our results show that LDH activity is significantly upregulated in cell cultures where the E4's effect was completely blocked by concomitant treatment either with ER alpha. and ER beta inhibitors (MPP and PHTPP, respectively), or ER(x. and ER beta inhibitors combined with 2-BR. Cell survival is significantly downregulated in cell cultures where the effect of E4 was blocked by ERp inhibitor (PHTTP) alone. The blockage of GRP30 receptor did affect neither LDH activity nor cell survival. MBP immunostaining is significantly upregulated in E4-pretreated groups at a concentration of 5mg/kg/day and 50 mg/kg/day E4, whereas the MBP-positive area OD ratio is significantly increased in all the E4-treated groups. E4's antioxidative actions mostly depend on ER alpha and ER beta, whereas neurogenesis and possibly promyelinating activities might be realized through ER beta.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据