Androgen signaling regulates the transcription of anti-Müllerian hormone via synergy with SRY-related protein SOX9A  

作　　者：Gang Zhai Tingting Shu Yuguo Xia Xia Jin Jiangyan He Zhan Yin 

机构地区：[1]State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China [2]University of Chinese Academy of Sciences, Beijing 100049, China [3]Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China

出　　处：《Science Bulletin》2017年第3期197-203,共7页科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China (31501857 to G.Z.and 31530077 to Z.Y.);the National Basic Research Program of China (2014CB138602 to Z.Y.)

摘　　要：Anti-Mullerian hormone （amh） is one of the earliest functional genes expressed during testicular differentiation. It has been suggested that androgen signaling regulates critical genes for the differentiation and development of the testis. To elucidate the exact regulatory mechanisms involved in arnh transcription mediated by androgen signaling, androgen signaling was manipulated in zebrafish by cytochrome P450 17al （cyplTal） knockout and Flutamide treatment. In cyp17a1-deficient and Flutamide-treated testes, up-regulated sry-box9a （soxga） and down-regulated amh were observed. Moreover, a physical association of the zebrafish androgen receptor （AR） and SOX9A was found. The interaction between AR and SOX9A was mediated via the DNA binding domain （DBD） of AR and the transactivation domain （TA） of SOX9A, and was further enhanced by 5-alpha dihydrotestosterone （DHT）, one of the most potent androgens. Intriguingly, together with SOX9A, androgen signaling synergistically promoted amh transcription, mainly through the proximal 1 kb of the amh promoter region. Taken together, our data demonstrate a critical mechanism underlying the direct synergy of androgen signaling and SOX9A in the regulation of amh transcription.Anti-Müllerian hormone(amh) is one of the earliest functional genes expressed during testicular differentiation. It has been suggested that androgen signaling regulates critical genes for the differentiation and development of the testis. To elucidate the exact regulatory mechanisms involved in amh transcription mediated by androgen signaling, androgen signaling was manipulated in zebrafish by cytochrome P45017a1(cyp17a1) knockout and Flutamide treatment. In cyp17a1-deficient and Flutamide-treated testes,up-regulated sry-box9a(sox9a) and down-regulated amh were observed. Moreover, a physical association of the zebrafish androgen receptor(AR) and SOX9 A was found. The interaction between AR and SOX9 A was mediated via the DNA binding domain(DBD) of AR and the transactivation domain(TA) of SOX9 A,and was further enhanced by 5-alpha dihydrotestosterone(DHT), one of the most potent androgens.Intriguingly, together with SOX9 A, androgen signaling synergistically promoted amh transcription,mainly through the proximal 1 kb of the amh promoter region. Taken together, our data demonstrate a critical mechanism underlying the direct synergy of androgen signaling and SOX9 A in the regulation of amh transcription.

关 键 词：Zebrafish Androgen signaling SOX9A Transcription amh 

分 类 号：R33[医药卫生—人体生理学]