Figure 2. The fate of testosterone in prostatic tissues.

Testosterone circulates in the blood and is bound to albumin, whereas free testosterone is introduced into prostate cells and is subsequently converted to DHT by 5-alpha-reductase. Binding of DHT to the AR induces dissociation from HSPs and receptor phosphorylation. The AR dimerizes and can bind to androgen-response elements in the promoter regions of target genes, leading to growth, survival and production of PSA. Enzalutamide, formerly called MDV3100, exerts its mechanism of action during several steps in the AR signaling pathway including inhibition of AR binding to androgens, inhibition of nuclear translocation of AR, inhibition of AR association to DNA, and AR amplification. As some of those aberrations may occur late in the disease, it is unknown at this point if enzalutamide will have a role upfront in the management of prostate cancer. Abbreviations: AR, androgen receptor; DHT, dihydrotestosterone; GTA, general transcription activation; HSP, heat-shock protein; SHBG, sex-hormone-binding globulin; AKT, akt serine/threonine kinase; DHEA, dihydroepiandrosterone; ERK, extracellular signal-regulated kinase; P, phosphorylated residues; PI3K, phosphoinositide 3-kinase; PTEN, phoshatase and tensin homolog.