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Abstract：
Molecular mechanisms by which androgens signal through the androgen receptor (AR) to maintain male fertility are poorly understood. Transgenic mice were produced expressing mutant ARs that can only (1) alter gene transcription through the classical response pathway (AR-C) or (2) activate kinase signaling cascades via the nonclassical pathway (AR-NC). AR-C is sufficient to produce sperm and fertility. Haploid germ cell production, the blood-testis barrier, and spermatid migration are supported by AR-NC. Gene expression essential for chromosome synapsis during meiosis requires AR-C. We identify targets of androgen signaling required for male fertility and provide a mechanistic explanation for meiotic germ cell arrest in the absence of androgen signaling. Prostate differentiation occurs with AR-C alone, but full development requires synergistic nonclassical signaling. Both AR signaling pathways are necessary for normal male reproductive tract development and function, validating our mouse models for studies of AR functions in other target tissues.
摘要：
雄激素通过雄激素受体（AR）发出信号以维持男性生育力的分子机制知之甚少。产生表达突变AR的转基因小鼠,其只能(1)通过经典应答途径(AR-C)改变基因转录或(2)通过非经典途径(AR-NC)激活激酶信号级联。AR-C足以产生精子和生育力。单倍体生殖细胞生产，血-睾丸屏障,和精子细胞迁移由AR-NC支持。减数分裂过程中染色体突触所必需的基因表达需要AR-C。我们确定了男性生育力所需的雄激素信号传导的目标，并在缺乏雄激素信号传导的情况下提供了减数分裂生殖细胞停滞的机制解释。单独使用AR-C时发生前列腺分化，但是全面发展需要协同的非经典信号。两种AR信号通路都是正常男性生殖道发育和功能所必需的，验证我们的小鼠模型，以研究其他靶组织中的AR功能。
