Androgens and the Androgen Receptor in Male Sex Development and Fertility

Abstract

The androgen receptor (AR) is a member of the nuclear receptor superfamily and acts as a transcription factor to modulate expression of target genes ((Chang et al., 1988a; Chang et al., 1988b; Lubahn et al., 1988a; Lubahn et al., 1988b; Tilley et al., 1989; Trapman et al., 1988). As a classical steroid hormone receptor, AR requires the binding of a ligand for activation of its function as a transcriptional modulator. The classical ligands known to activate AR include testosterone (T) and its metabolites, such as 5α-dihydrotestosterone (DHT). Once a ligand is bound, AR undergoes a change in conformation and phosphorylation status, allowing the receptor to bind to target gene DNA response elements. Recruitment of specific coregulators alters the regulatory effect AR has on target gene expression (see Chapter 4 of this volume by Heinlein et al.). However, it has been proposed that androgens act independently of AR to produce non-genomic effects (Rommerts, 1998) (see Chapter 5 of this volume by Heinlein and Chang), and that AR may function without binding to DNA (Slagsvold et al., 2001). AR is expressed nearly ubiquitously in mammalian tissues (Kimura et al., 1993; Sar et al., 1990; Tilley et al., 1990), and is known to play various biological roles in areas including development, sexual and reproductive function, immune function, and homeostasis (Quigley, 1998).