Androgens regulate the permeability of the blood-tests barrier
Androgens regulate the permeability of the blood-tests barrier
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DOI：
10.1073/pnas.0506084102
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发表时间：
2005-11-15
影响因子：
11.1
通讯作者：
Braun, RE
中科院分区：
文献类型：
--
作者：
Meng, J;Holdcraft, RW;Braun, RE
在哺乳动物睾丸内，体细胞支持细胞之间的特化紧密连接在细胞内产生基底和顶端极性，限制细胞之间的分子运动，并将生精上皮分隔成基底和近腔室。这些紧密连接形成了血睾屏障的基础，这种结构的功能和动态调节知之甚少。在这项研究中，我们使用微阵列基因表达谱，以确定基因的转录水平改变的小鼠模型中的条件雄激素不敏感。我们发现，睾酮，通过其受体在支持细胞中表达，调节表达的claudin 3，编码一个短暂的组成部分，新形成的紧密连接。支持细胞特异性雄激素受体消融导致血-睾丸屏障对生物素的渗透性增加，表明claudin 3调节小分子穿过支持细胞紧密连接的运动。这些结果表明，雄激素在支持细胞中的作用调节生殖细胞的分化，部分是通过控制生精上皮的微环境。我们的研究还表明，男性避孕的激素策略可能会干扰血睾屏障。
Within the mammalian testis, specialized tight junctions between somatic Sertoli cells create basal and apical polarity within the cells, restrict movement of molecules between cells, and separate the seminiferous epithelium into basal and adluminal compartments. These tight junctions form the basis of the blood-testis barrier, a structure whose function and dynamic regulation is poorly understood. In this study, we used microarray gene expression profiling to identify genes with altered transcript levels in a mouse model for conditional androgen insensitivity. We show that testosterone, acting through its receptor expressed in Sertoli cells, regulates the expression of claudin 3, which encodes a transient component of newly formed tight junctions. Sertoli cell-specific ablation of androgen receptor results in increased permeability of the blood-testis barrier to biotin, suggesting claudin 3 regulates the movement of small molecules across the Sertoli cell tight junctions. These results suggest that androgen action in Sertoli cells regulates germ cell differentiation, in part by controlling the microenvironment of the seminiferous epithelium. Our studies also indicate that hormonal strategies for male contraception may interfere with the blood-testis barrier.