Mechanisms and clinical relevance of androgens and androgen receptor actions.
Androgens, principally testosterone and 5alpha-dihydrotestosterone, affect a number of diverse responses in a variety of peripheral target tissues. Their biological actions are mediated by a ligand-dependent nuclear transcription factor, the androgen receptor (AR). The AR is a member of the steroid hormone receptor family, which is found in a variety of tissues, and changes throughout development, aging, and malignant transformation. Recently, cloning and characterization of several AR co-regulators have allowed for cellular and molecular analysis of many different aspects of androgen physiology and pathophysiology. The transcriptional activity of AR is regulated by AR co-regulators, which influence the ligand selectivity and DNA binding capacity of AR. Aberrant co-regulator function due to mutation or altered expression levels may be a contributing factor in the progression of AR-mediated diseases. However, in spite of the intensity of research activity in this area, many interesting questions regarding the fundamental mechanism of AR and co-regulators on androgen-related diseases, such as osteoporosis and androgen insensitive syndrome remain unsolved. In this review, we provide a brief overview of genomic and non-genomic androgens/AR actions, as well as the regulation of their co-regulators. We also explore several intriguing aspects of the molecular biology of AR and co-regulators that are related to clinical diseases.
Kang
Hong-Yo
HY
Graduate Institute of Clinical Medical Sciences, Chang Gung University, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Tsai
Meng-Yin
MY
Chang
Chawnshang
C
Huang
Ko-En
KE
D000728:Androgens / Q000502:physiology*; D001842:Bone and Bones / Q000502:physiology; D006801:Humans; D007248:Infertility, Male / Q000503:physiopathology; D008297:Male; D011471:Prostatic Neoplasms / Q000503:physiopathology; D011944:Receptors, Androgen / Q000502:physiology*; D012733:Sex Differentiation / Q000502:physiology
D000728:Androgens; D011944:Receptors, Androgen