Lin Yung Ming, Tsai Chih Chien, Chung Chia Ling, Chen Pei Rong, Sun H Sunny, Tsai Shaw Jenq, Huang Bu Miin
Department of Urology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Int J Androl. 2010 Jun 1;33(3):545-53. doi: 10.1111/j.1365-2605.2009.00966.x. Epub 2009 Jun 7.
Fibroblast growth factor 9 (FGF9) is a potent mitogen and survival factor required for morphogenesis during embryonic development and numerous biological functions at adulthood. The reproductive phenotype of mice lacking Fgf9 gene exhibits male to female sexual reversal, suggesting a crucial role of Fgf9 in male sex determination. Our previous study showed that polymorphic microsatellite of FGF9 genes is associated with 46XY female with ambiguous genitalia, implying that the aberrant expression of FGF9 might affect androgen secretion. In this study, we aimed to investigate the effect of FGF9 on testosterone production in mouse Leydig cell and to study the signalling pathways by which FGF9 modulate steroidogenesis. Our results show that mRNAs of Fgf9 and Fgfr isoforms (Fgfr2IIIc, Fgfr3 and Fgfr4) were all expressed in mouse Leydig cells. FGF9 significantly stimulates mouse Leydig cell testosterone production in a dose- and time-dependent manner. Ras-MAPK, PI3K and PKA signalling pathways are involved in the FGF9-induced steroidogenesis. These results provide supportive evidence linking the aberrant expression of FGF9 to human gonadal dysgenesis and suggest a role of FGF9 in postnatal testicular development.
成纤维细胞生长因子9（FGF9）是一种强效的促有丝分裂剂和存活因子，在胚胎发育期间的形态发生以及成年期的多种生物学功能中发挥作用。缺乏Fgf9基因的小鼠的生殖表型表现为雄性向雌性的性反转，这表明Fgf9在雄性性别决定中起关键作用。我们之前的研究表明，FGF9基因的多态性微卫星与生殖器模糊的46XY女性相关，这意味着FGF9的异常表达可能会影响雄激素的分泌。在本研究中，我们旨在研究FGF9对小鼠睾丸间质细胞睾酮产生的影响，并研究FGF9调节类固醇生成的信号通路。我们的结果表明，Fgf9和Fgfr亚型（Fgfr2IIIc、Fgfr3和Fgfr4）的mRNA均在小鼠睾丸间质细胞中表达。FGF9以剂量和时间依赖性方式显著刺激小鼠睾丸间质细胞的睾酮产生。Ras-MAPK、PI3K和PKA信号通路参与了FGF9诱导的类固醇生成。这些结果为将FGF9的异常表达与人类性腺发育不全联系起来提供了支持性证据，并表明FGF9在出生后睾丸发育中发挥作用。
