Department of Basic Sciences, The Commonwealth Medical College, Scranton, PA, USA.
Life Sci. 2011 Mar 28;88(13-14):565-71. doi: 10.1016/j.lfs.2011.01.021. Epub 2011 Jan 31.
Androgens are involved in the development of several tissues, including prostate, skeletal muscle, bone marrow, hair follicles, and brain. Most of the biological effects of the androgens are mediated through an intracellular transcription factor, the androgen receptor (AR) at the level of gene regulation. Several types of mutations in the AR gene have been linked to endocrine dysfunctions. The expansion of CAG codon repeat, coding for a polyglutamine (PolyQ) tract in the N-terminal domain is one such mutation. The polyQ chain length impacts AR's ability to interact with critical coregulators, which in turn modulates its transcriptional efficacy. Pathologic manifestations of variations in polyQ chain length have been associated with prostate cancer susceptibility, and the Spinal and Bulbar Muscular Atrophy (SBMA), a neurodegenerative disease. In this review article, we discuss multiple aspects of the role of polyQ chain length in the actions of the AR, their importance in prostate cancer development and progression, and SBMA with an aim to understand the underlying mechanisms involved in these diseases, which can be targeted for future therapeutic approaches.
雄激素参与了包括前列腺、骨骼肌、骨髓、毛囊和大脑在内的多种组织的发育。雄激素的大多数生物学效应都是通过细胞内转录因子——雄激素受体（AR）在基因调控水平上介导的。AR 基因的几种突变与内分泌功能障碍有关。CAG 密码子重复的扩展，编码 N 端结构域的多聚谷氨酰胺（PolyQ）序列，就是这样一种突变。PolyQ 链长影响 AR 与关键共调节因子相互作用的能力，进而调节其转录功效。PolyQ 链长的变化与前列腺癌易感性和脊髓延髓肌肉萎缩症（SBMA）——一种神经退行性疾病的病理表现有关。在这篇综述文章中，我们讨论了 PolyQ 链长在 AR 作用中的多个方面，它们在前列腺癌发展和进展中的重要性，以及 SBMA，旨在了解这些疾病中涉及的潜在机制，这些机制可以作为未来治疗方法的靶点。
