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FOXA3，睾丸类固醇生成中Nur77表达和活性的负调节因子。

FOXA3, a Negative Regulator of Nur77 Expression and Activity in Testicular Steroidogenesis.

作者信息

Kim Hansle, Kumar Sudeep, Lee Keesook

机构信息

School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.

出版信息

Int J Endocrinol. 2021 Mar 3;2021:6619447. doi: 10.1155/2021/6619447. eCollection 2021.

DOI:10.1155/2021/6619447
PMID:33763129
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7946474/
Abstract

Biosynthesis of testosterone occurs mainly in the testicular Leydig cells. Nur77, an orphan nuclear receptor that is expressed in response to the luteinizing hormone/cyclic adenosine monophosphate (LH/cAMP) signaling pathway, is one of the key factors that regulate steroidogenesis in Leydig cells. The function of Nur77 is modulated through interaction with other proteins. FOXA3, a transcription factor that is crucial for male fertility, is also expressed in Leydig cells. Here, we sought to elucidate the role of FOXA3 in testicular steroidogenesis by focusing on its interaction with Nur77. LH/cAMP signaling induces the onset of steroidogenesis in Leydig cells but has a repressive effect on the expression of FOXA3. Overexpression of FOXA3 in MA-10 Leydig cells repressed cAMP-induced expression of and its target steroidogenic genes (, , and ). Furthermore, FOXA3 suppressed Nur77 transactivation of the promoter of steroidogenic genes. In mouse primary Leydig cells, adenovirus-mediated overexpression of FOXA3 had similar effects and resulted in decreased production of testosterone. Taken together, these results suggest the role of FOXA3 in the regulation of steroidogenic genes in Leydig cells and fine-tuning steroidogenesis in the testis.

摘要

睾酮的生物合成主要发生在睾丸间质细胞中。Nur77是一种孤儿核受体，其表达受促黄体生成素/环磷酸腺苷（LH/cAMP）信号通路的调控，是调节间质细胞类固醇生成的关键因素之一。Nur77的功能通过与其他蛋白质的相互作用来调节。FOXA3是一种对男性生育至关重要的转录因子，也在间质细胞中表达。在此，我们通过关注FOXA3与Nur77的相互作用，试图阐明FOXA3在睾丸类固醇生成中的作用。LH/cAMP信号诱导间质细胞中类固醇生成的起始，但对FOXA3的表达具有抑制作用。在MA-10间质细胞中过表达FOXA3可抑制cAMP诱导的 及其靶类固醇生成基因（ 、 和 ）的表达。此外，FOXA3抑制类固醇生成基因启动子的Nur77反式激活。在小鼠原代间质细胞中，腺病毒介导的FOXA3过表达具有类似的作用，并导致睾酮生成减少。综上所述，这些结果表明FOXA3在调节间质细胞类固醇生成基因以及微调睾丸类固醇生成中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9276/7946474/c8f86488c8db/IJE2021-6619447.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9276/7946474/a5f5d7bea085/IJE2021-6619447.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9276/7946474/6ee6782138d9/IJE2021-6619447.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9276/7946474/349a7fc443d3/IJE2021-6619447.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9276/7946474/911f062b64f0/IJE2021-6619447.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9276/7946474/67277dd5afe9/IJE2021-6619447.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9276/7946474/c8f86488c8db/IJE2021-6619447.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9276/7946474/a5f5d7bea085/IJE2021-6619447.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9276/7946474/6ee6782138d9/IJE2021-6619447.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9276/7946474/349a7fc443d3/IJE2021-6619447.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9276/7946474/911f062b64f0/IJE2021-6619447.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9276/7946474/67277dd5afe9/IJE2021-6619447.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9276/7946474/c8f86488c8db/IJE2021-6619447.006.jpg

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