Androgen Receptor Structure, Function and Biology: From Bench to Bedside

Abstract

The actions of androgens such as testosterone and dihydrotestosterone are mediated via the androgen receptor (AR), a ligand-dependent nuclear transcription factor and member of the steroid hormone nuclear receptor family. Given its widespread expression in many cells and tissues, the AR has a diverse range of biological actions including important roles in the development and maintenance of the reproductive, musculoskeletal, cardiovascular, immune, neural and haemopoietic systems. AR signalling may also be involved in the development of tumours in the prostate, bladder, liver, kidney and lung. Androgens can exert their actions via the AR in a DNA binding-dependent manner to regulate target gene transcription, or in a non-DNA binding-dependent manner to initiate rapid, cellular events such as the phosphorylation of 2(nd) messenger signalling cascades. More recently, ligand-independent actions of the AR have also been identified. Given the large volume of studies relating to androgens and the AR, this review is not intended as an extensive review of all studies investigating the AR, but rather as an overview of the structure, function, signalling pathways and biology of the AR as well as its important role in clinical medicine, with emphasis on recent developments in this field.

Figure 1.

Functional domains of the androgen receptor (AR): N-terminal domain, DNA binding domain (DBD), Ligand binding domain. (H – hinge region, AF-1 – transcriptional activating function 1, AF-2 – transcriptional activating function 2, NLS – nuclear localisation signal, NES – nuclear export signal)

Figure 2.

Mechanisms of ligand-dependent androgen receptor (AR) action: (1) DNA binding-dependent (DBD) and (2) non-DNA binding (DBD)-dependent. (AP-1 – activator protein 1) Reproduced from Rana et al. (ref. 3) with permission.