The biological and clinical advances of androgen receptor function in age-related diseases and cancer [Review]

Hormonal alterations with aging contribute to the pathogenesis of several diseases. Androgens mediate their effects predominantly through binding to the androgen receptor (AR), a member of the ligand-dependent nuclear receptor superfamily. By androgen treatment, AR is recruited to specific genomic loci dependent on tissue specific pioneer factors to regulate target gene expression. Recent studies have revealed the epigenetic modulation by AR-associated histone modifiers and the roles of non-coding RNAs in AR signaling. Androgens are male sex hormone to induce differentiation of the male reproductive system required for the establishment of adult sexual function. As shown by several reports using AR knockout mouse models, androgens also have anabolic functions in several tissues such as bone, muscle and central nervous systems. Notably, AR has a central role in prostate cancer progression. Prostate cancer is the most frequently diagnosed cancer in men. Androgen-deprivation therapy for cancer patients and decline of serum androgen with aging promote several diseases associated with aging and quality of life of older men such as osteoporosis, sarcopenia and dementia. Thus, androgen replacement therapy for treating late onset hypogonadism (LOH) or new epigenetic regulators have the potential to overcome the symptoms caused by the low androgen, although adverse effects for cardiovascular diseases have been reported. Given the increasing longevity and consequent rise of age-related diseases and prostate cancer patients, a more understanding of the AR actions in male health remains a high research priority.

Endocrine journal. 2017 Aug 19 [Epub ahead of print]

Ken-Ichi Takayama

Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.