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Oestrogen regulates SOX9 bioavailability by rapidly activating ERK1/2 and stabilising microtubules in a human testis-derived cell line
Experimental Cell Research ( IF 3.3 ) Pub Date : 2020-11-30 , DOI: 10.1016/j.yexcr.2020.112405
Melanie K. Stewart , Deidre M. Mattiske , Andrew J. Pask

Nuclear SOX9 is essential for Sertoli cell differentiation and the development of a testis. Exposure of Sertoli cells to exogenous oestrogen causes cytoplasmic retention of SOX9, inhibiting testis development and promoting ovarian development. The cytoplasmic localisation of SOX9 requires a stabilised microtubule network and a key MAPK complex, ERK1/2, is responsive to oestrogen and known to affect the microtubule network. We hypothesised that oestrogen could stabilise microtubules through the activation of ERK1/2 to promote the cytoplasmic retention of SOX9. Treatment of human testis-derived NT2/D1 cells for 30 min with oestrogen rapidly activated ERK1/2, stabilised the microtubule network and increased cytoplasmic localisation of SOX9. The effects of oestrogen on SOX9 and tubulin were blocked by the ERK1/2 inhibitor U0126, demonstrating that ERK1/2 mediates the stabilisation of microtubules and cytoplasmic retention of SOX9 by oestrogen. Together, these data revealed a previously unknown mechanism for oestrogen in impacting MAPK signalling to block SOX9 bioavailability and the differentiation of Sertoli cells.



中文翻译:

雌激素通过快速激活人睾丸来源的细胞系中的ERK1 / 2和稳定微管来调节SOX9的生物利用度。

核SOX9对支持细胞分化和睾丸发育至关重要。Sertoli细胞暴露于外源性雌激素会导致SOX9保留在细胞质中,从而抑制睾丸发育并促进卵巢发育。SOX9的胞质定位需要稳定的微管网络,关键的MAPK复合物ERK1 / 2对雌激素有反应,并且已知会影响微管网络。我们假设雌激素可以通过激活ERK1 / 2来促进SOX9的胞质保留而稳定微管。用雌激素处理人睾丸来源的NT2 / D1细胞30分钟可快速激活ERK1 / 2,稳定微管网络并增加SOX9的细胞质定位。ERK1 / 2抑制剂U0126阻断了雌激素对SOX9和微管蛋白的作用,证明ERK1 / 2通过雌激素介导了微管的稳定和SOX9的胞质保留。总之,这些数据揭示了雌激素影响MAPK信号传导以阻断SOX9生物利用度和Sertoli细胞分化的未知机制。

更新日期:2020-12-14
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