Expression and functional state of the corticosteroid receptors and 11β-hydroxysteroid dehydrogenase type 2 in Schwann cells
Expression and functional state of the corticosteroid receptors and 11β-hydroxysteroid dehydrogenase type 2 in Schwann cells
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DOI：
10.1210/en.2005-1625
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发表时间：
2006-09-01
期刊：
影响因子：
4.8
通讯作者：
Cadepond, Francoise
中科院分区：
文献类型：
--
作者：
Groyer, Ghislaine;Eychenne, Bernard;Cadepond, Francoise
为了探讨类固醇受体在类固醇对雪旺细胞(SC)髓鞘形成和生长的影响中的作用，我们测定了在增殖和静止条件下培养的大鼠雪旺细胞(SC)中皮质类固醇(糖皮质类固醇和矿化皮质类固醇)受体(GR和MR)和性类固醇(孕酮、雄激素、雌激素α和β)受体的mRNA含量和转录活性。我们发现SC中性类固醇受体没有表达或活性很低，通过实时定量聚合酶链式反应测定的mRNA浓度和瞬时表达报告质粒的转录活性显示了这一点。这些数据和对SC系的结合研究表明，性类固醇受体的水平是限制因素。GR表达清晰(相当于8000个序列/ng总RNA)，具有一定的功能性。GR mRNA水平没有明显改变，但与静止细胞相比，增殖细胞的转录效率增加。在两种培养条件下，MR也在mRNA水平上显著表达(相当于450个序列/ng总RNA)。在SC中没有观察到MR转录活性，但在SC系中检测到低特异性的醛固酮结合。11β-羟类固醇脱氢酶2(HSD2)是一种糖皮质激素失活的酶，在静止期SC中有较强的表达和活性，而在增殖细胞中，HSD2的活性和mRNA浓度显著降低。这些数据支持HSD2调节神经干细胞中糖皮质激素浓度的生理作用。
To investigate the role of steroid receptors in mediating the reported effects of steroids on Schwann cell (SC) myelination and growth, we determined mRNA contents and transcriptional activities of the corticosteroid (glucocorticosteroid and mineralocorticosteroid) receptors (GR and MR) and sex steroid ( progesterone, androgen, and estrogen alpha and beta) receptors in rat SC cultured under proliferative ( in the presence of insulin and forskolin, which induces a high intracellular cAMP content) and quiescent conditions. We found no or very low expression and activity of the sex steroid receptors, as shown by mRNA concentrations determined with real-time PCR and transcriptional activities using transient expression of reporter plasmids in SC. These data and binding studies in SC lines demonstrated that the levels of the sex steroid receptors were the limiting factors. GR was clearly expressed (similar to 8000 sequences/ng total RNA) and functional. No significant modification in GR mRNA levels was observed, but an increase in transcriptional efficiency was recorded in proliferating cells compared with quiescent cells. MR was also significantly expressed at the mRNA level (similar to 450 sequences/ng total RNA) under the two culture conditions. No MR transcriptional activity was observed in SC, but a low specific binding of aldosterone was detected in SC lines. 11 beta-Hydroxysteroiddehydrogenase type 2 (HSD2), an enzyme that inactivates glucocorticoids, was strongly expressed and active in quiescent SC, although in proliferating cells, HSD2 exhibited a strong decrease in activity and mRNA concentration. These data support a physiological role for HSD2 regulation of glucocorticosteroid concentrations in nerve SC.