Essential Roles of Androgen Signaling in Wolffian Duct Stabilization and Epididymal Cell Differentiation
Essential Roles of Androgen Signaling in Wolffian Duct Stabilization and Epididymal Cell Differentiation
复制标题
DOI：
10.1210/en.2010-1121
复制
发表时间：
2011-04-01
期刊：
影响因子：
4.8
通讯作者：
Yamada, Gen
中科院分区：
文献类型：
--
作者：
Murashima, Aki;Miyagawa, Shinichi;Yamada, Gen
附睾是男性的附属器官，在雄激素的控制下，具有精子成熟和储存的功能。附睾的发育也依赖于雄激素。Wolffian管（WD），附睾的原基，在男性和女性胚胎中形成;然而，它仅在男性胚胎中由睾丸雄激素稳定。雄激素驱动WD随后分化为附睾。虽然雄激素在WD雄性化和附睾功能中的重要作用已经确定，但对这些过程中由雄激素信号精确调控的细胞事件知之甚少。目前还不清楚雄激素信号，特别是在上皮细胞，是否有进一步的功能，附睾上皮细胞分化。在这项研究中，我们研究了细胞死亡和增殖控制雄激素信号通过雄激素受体（AR）在WD稳定。使用AR基因敲除小鼠的分析显示，雄激素信号传导抑制了该过程中的上皮细胞死亡。AP 2 α-Cre的分析; AR（flox/Y）小鼠，其中AR功能缺失的WD上皮，揭示了上皮AR是不需要的WD稳定，但需要上皮细胞分化的附睾。具体而言，上皮AR的损失显着降低了p63的表达，这是必不可少的基底细胞在附睾上皮的分化。我们还询问了体外AR对p63基因（Trp 63）调节的可能性，发现p63可能是AR调节的直接靶点。（内分泌学152：1640-1651，2011）
The epididymis is a male accessory organ and functions for sperm maturation and storage under the control of androgen. The development of the epididymis is also androgen dependent. The Wolffian duct (WD), anlagen of the epididymis, is formed in both male and female embryos; however, it is stabilized only in male embryos by testicular androgen. Androgen drives subsequent differentiation of the WD into the epididymis. Although the essential roles of androgen in WD masculinization and epididymal function have been established, little is known about cellular events regulated precisely by androgen signaling during these processes. It is also unclear whether androgen signaling, especially in the epithelia, has further function for epididymal epithelial cell differentiation. In this study we examined the cellular death and proliferation controlled by androgen signaling via the androgen receptor (AR) in WD stabilization. Analyses using AR knockout mice revealed that androgen signaling inhibits epithelial cell death in this process. Analysis of AP2 alpha-Cre;AR(flox/Y) mice, in which AR function is deleted in the WD epithelium, revealed that epithelial AR is not required for the WD stabilization but is required for epithelial cell differentiation in the epididymis. Specifically, loss of epithelial AR significantly reduced expression of p63 that is essential for differentiation of basal cells in the epididymal epithelium. We also interrogated the possibility of regulation of the p63 gene (Trp63) by AR in vitro and found that p63 is a likely direct target of AR regulation. (Endocrinology 152: 1640-1651, 2011)