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

Gang Zhai; Tingting Shu; Yuguo Xia; Xia Jin; Jiangyan He; Zhan Yin

doi:10.1016/j.scib.2017.01.007

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

Sci Bull (Beijing). 2017 Feb 15;62(3):197-203. doi: 10.1016/j.scib.2017.01.007. Epub 2017 Jan 10.

Authors

Gang Zhai¹, Tingting Shu², Yuguo Xia³, Xia Jin¹, Jiangyan He¹, Zhan Yin⁴

Affiliations

¹ State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
² State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, China.
³ Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China.
⁴ State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China. Electronic address: zyin@ihb.ac.cn.

PMID: 36659404
DOI: 10.1016/j.scib.2017.01.007

Abstract

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 P450 17a1 (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 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 1kb 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.

Keywords: Androgen signaling; SOX9A; Transcription; Zebrafish; amh.