Androgen Receptor
摘要
Androgen receptor (AR) belongs to the steroid hormone receptor family of the nuclear receptor superfamily and acts as a hormone-controlled transcription factor that conveys the messages of both natural and synthetic androgens to the genes and gene programs. The androgen-regulated genes have a central role in the development and maintenance of the male phenotype and reproductive physiology. AR gene resides on the X chromosome, and mutations in the gene lead to a wide array of androgen insensitivity disorders in males. AR-mediated gene regulation is a rigorously regulated process that involves a coordinated interaction of AR with other DNA sequence-specific transcription factors, such as pioneer factor forkhead box1 and coregulator proteins, including PIAS1. AR signaling starts in the cytosol where hormone binding releases the receptor from a chaperone complex, leading to receptor oligomerization and nuclear translocation and binding to androgen response elements in the regulatory regions of AR target genes. Genome-wide methods have indicated that the AR regulates transcription mostly from the distal chromatin-binding sites, enhancers, through long-range chromatin interactions with gene promoters. In addition to androgens, the AR activity is regulated by several posttranslational modifications, such as SUMOylation, which influence the chromatin binding, protein stability, and interaction of the receptor with other proteins. Recent evidence demonstrating that androgens can enhance skeletal muscle strength specifically via a cell membrane receptor underscores the physiological importance of nongenomic androgen signaling, in addition to the classical genomic pathway.