The AR belongs to the steroid receptor subfamily of the nuclear receptor superfamily. Its function is regulated by the binding of androgens, which initiates sequential conformation changes of the receptor that affects receptor-protein and receptor-DNA interactions. Endogenous androgens are mainly testosterone and DHT. AR is expressed in cells of a wide range of tissues, throughout the entire body, beyond primary and secondary sexual organs.
The AR gene is more than 90kb long and codes for a protein of 919 amino acids. Only one AR gene has been identified in humans which is located on chromosome X. It comprises four main regions, see figure 1:
# N-terminal domain (NTD) which serves a modulatory function.
# DNA-binding domain (DBD) which recognises and binds to androgen response elements (ARE) in target gene sequence.
# Ligand binding domain (LBD) which is responsible for ligand recognition and binding.
# A small hinge region between the DBD and LBD.
Two functions have been identified in AR that have critical roles in the regulation of target gene transactivation, the N-terminal activation function 1 (AF1) and the C-terminal activation function 2 (AF2). AF1 is ligand-independent and plays the primary role in target gene transactivation. The AF2 is a ligand-dependent and only shows limited function.