Postnatal changes of steroid receptor coactivator-1 immunoreactivity in rat cerebellar cortex

Postnatal changes of steroid receptor coactivator-1 immunoreactivity in rat cerebellar cortex
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DOI:
10.1089/thy.2005.15.314
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发表时间:
2005-04-01
期刊:
影响因子:
6.6
通讯作者:
Koibuchi, N
Koibuchi, N
中科院分区:
医学1区
文献类型:
--
作者:
Yousefi, B;Jingu, H;Koibuchi, N

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类固醇受体辅活化子-1(SRC-1)与核激素受体(NRs)相互作用,以配体依赖的方式介导其作用。在这些配体中,甲状腺激素(TH)对大脑发育尤为关键。许多TH靶基因的表达只在一个有限的关键期内受到TH的调控,尽管TH受体(TR)的表达在这段时间后不会发生很大变化。要改变这种敏感性,可能还涉及其他因素。因此,我们通过免疫组织化学和Western blotting检测了SRC-1在大鼠小脑出生后发育过程中的表达变化。从出生后2天到30天,浦肯野细胞中持续有强的SRC-1免疫反应。SRC-1免疫反应也持续存在于内颗粒细胞层。但在P2和P7的外颗粒细胞层中呈阴性,而在P15的迁移前带中检测到微弱的IR。P15后在分子层检测到SRC-1 IR。这些结果表明,尽管TRR在发育中的小脑中几乎无处不在地表达,但TH的敏感性在每个细胞亚群中可能有所不同。Western blotting显示,SRC-1蛋白水平在P15时最高,此时可能有明显的作用。综上所述,SRC-1的差异表达可能在调节小脑发育过程中的TH活动中起关键作用。
Steroid receptor coactivator-1 (SRC-1) interacts with nuclear hormone receptors (NRs) to mediate their action in a ligand-dependent manner. Among such ligands, thyroid hormone (TH) is particularly crucial for brain development. The expression of many TH target genes is regulated by TH only for a limited critical period, although TH receptor (TR) expression is not greatly altered after such period. To alter TH sensitivity, other factors may be involved. We thus examined the changes in SRC-1 expression during postnatal development in the rat cerebellum by immunohistochemistry and Western blotting. Strong SRC-1 immunoreactivity (IR) was constantly seen in Purkinje cell from postnatal days (P) 2 to P30. SRC-1 IR was also constantly observed in the internal granule cell layer. However, it was negative in the external granule cell layer at P2 and P7, whereas a weak IR was detected in the premigratory zone at P15. SRC-1 IR was detected in the molecular layer after P15. These results indicate that although TR is almost ubiquitously expressed in the developing cerebellum, the TH sensitivity could vary in each subset of cells. By Western blotting, SRC-1 protein level was greatest at P15, at which time TH action may be obvious. Taken together, the differential expression of SRC-1 may be crucial in mediating TH action during cerebellar development.