Lee Dong Kun, Chang Chawnshang
George Whipple Laboratory for Cancer Research, Department of Pathology, and Cancer Center, University of Rochester Medical Center, Rochester, New York 14642, USA.
J Clin Endocrinol Metab. 2003 Sep;88(9):4043-54. doi: 10.1210/jc.2003-030261.
The androgen-androgen receptor (AR) signaling pathway plays a key role in proper development and function of male reproductive organs, such as prostate and epididymis, as well as nonreproductive organs, such as muscle, hair follicles, and brain. Abnormalities in the androgen-AR signaling pathway have been linked to diseases, such as male infertility, Kennedy's disease, and prostate cancer. Regulation of AR activity can be achieved in several different ways: modulation of AR gene expression, androgen binding to AR, AR nuclear translocation, AR protein stability, and AR trans-activation. This review covers mechanisms implicated in the control of AR protein expression and degradation, and their potential linkage to the androgen-related diseases. A better understanding of such mechanisms may help us to design more effective androgens and antiandrogens to battle androgen-related diseases.
雄激素-雄激素受体(AR)信号通路在男性生殖器官(如前列腺和附睾)以及非生殖器官(如肌肉、毛囊和大脑)的正常发育和功能中起着关键作用。雄激素-AR信号通路的异常与男性不育、肯尼迪病和前列腺癌等疾病有关。AR活性的调节可以通过几种不同的方式实现:AR基因表达的调节、雄激素与AR的结合、AR的核转位、AR蛋白的稳定性以及AR的反式激活。本综述涵盖了与AR蛋白表达和降解控制相关的机制,以及它们与雄激素相关疾病的潜在联系。更好地理解这些机制可能有助于我们设计更有效的雄激素和抗雄激素药物来对抗雄激素相关疾病。