Molecular mechanisms of masculinization: role of growth factor signaling and androgen regulation

2015 Fiscal Year Final Research Report

• Project/Area Number: 25860771
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: Wakayama Medical University
• Principal Investigator: Murashima Aki 和歌山県立医科大学, 先端医学研究所, 特別研究員 (50637105)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: アンドロゲン受容体 / 細胞増殖因子 / ウォルフ管 / 生殖内分泌学 / 遺伝子改変マウス / アンドロゲン

Outline of Final Research Achievements

Wolffian duct (WD) development is one of the most prominent developmental processes which lead to masculinization of the reproductive tract. Androgen is the most important factor to promote masculinization processes including WD elongation. In this study, the functions of several growth factor signaling and molecular mechanisms of androgen regulation were analyzed during WD development. Conditional knockout studies revealed that Sonic hedgehog (Shh) and Fibroblast growth factor (Fgf) signaling pathways play pivotal roles in WD development. In vitro culture system revealed that Wnt signaling regulated WD masculinization. Further analyses revealed that androgen regulates Wnt signaling through the suppression of Wnt antagonist expression. This study demonstrated the function of growth factor signaling in WD development and identified Wnt signaling as a down-stream target of androgen signaling.

Free Research Field

発生生物学、内分泌学、分子生物学