Yong E L, Ghadessy F, Wang Q, Mifsud A, Ng S C
Department of Obstetrics and Gynaecology, National University of Singapore.
Rev Reprod. 1998 Sep;3(3):141-4. doi: 10.1530/ror.0.0030141.
Male sex steroids (androgens) are important for maintaining sperm production and growth of the accessory sex organ, the prostate gland. This article examines the role of the androgen receptor (AR) in the control of spermatogenesis and focusses on the N-terminal transactivation domain of the receptor, a poorly studied region that is essential for receptor function. This domain is of great interest because of its causative relationship to a fatal neuromuscular disease, spinal bulbar muscular atrophy (Kennedy's syndrome). Genetic screening of the transactivation domain of the AR gene of 153 patients presenting solely with defective spermatogenesis and male infertility, and of over 72 healthy fertile controls was performed. Up to 20% of infertile males have reduced androgenicity caused by an increase in length of a polymorphic trinucleotide (CAG) repeat segment, encoding a polyglutamine tract, of the androgen receptor. The increased risk of male infertility associated with long CAG lengths is associated with reduced risk of prostate cancer. Conversely, short polyglutamine tracts are associated with increased risk of prostate cancer but a reduced risk of male infertility. Thus depressed spermatogenesis and prostate cancer represent opposite ends of the spectrum of androgen receptor transactivation function. Improved understanding of androgen receptor action in these two important public health concerns could lead to rational and effective prevention and therapy.
男性性类固醇（雄激素）对于维持精子生成以及附属性腺——前列腺的生长至关重要。本文探讨了雄激素受体（AR）在精子发生调控中的作用，并聚焦于该受体的N端反式激活结构域，这是一个研究较少但对受体功能至关重要的区域。由于该结构域与一种致命的神经肌肉疾病——脊髓延髓肌肉萎缩症（肯尼迪综合征）存在因果关系，因此备受关注。对153例仅表现为精子发生缺陷和男性不育的患者以及72例以上健康可育对照者的AR基因反式激活结构域进行了基因筛查。高达20%的不育男性因雄激素受体中编码多聚谷氨酰胺序列的多态性三核苷酸（CAG）重复片段长度增加而导致雄激素活性降低。CAG长度较长与男性不育风险增加相关，同时与前列腺癌风险降低相关。相反，短的多聚谷氨酰胺序列与前列腺癌风险增加相关，但与男性不育风险降低相关。因此，精子发生受抑制和前列腺癌代表了雄激素受体反式激活功能谱的两端。更好地理解雄激素受体在这两个重要公共卫生问题中的作用，可能会带来合理有效的预防和治疗方法。
