1. therapy and to block androgen action
Figure 1 Androgen synthesis and signalling pathways: drugs used for androgen deprivation
therapy and to block androgen action
Figure 1 | Androgen synthesis and signalling pathways: drugs used for androgen deprivation therapy and to block androgen action. The hypothalamic-pituitary-testicular axis controls testicular androgen synthesis via the actions of luteinizing hormone (LH) on the testes. Furthermore, the hypothalamic-pituitary-adrenal axis controls androgen precursor synthesis via the actions of adrenocorticotropic hormone (ACTH) on the adrenals. Once synthesized, the androgens testosterone or dihydrotestosterone (DHT) then bind to the androgen receptor (AR) in the prostate; this complex then dimerizes, translocates to the nucleus and interacts with androgen response elements (AREs) in the promoter or distal sites of target genes. This action regulates the expression of androgen-dependent target genes that control prostate survival, growth and PSA secretion in addition to multiple other signalling pathways. Drugs that reduce androgen synthesis and signalling are used clinically to induce androgen deprivation in patients with prostate cancer. These drugs include gonadotropin‑releasing hormone (GnRH) inhibitors that inhibit LH action, glucocorticoids that inhibit corticotropin-releasing hormone (CRH) release from the hypothalamus and ACTH from the pituitary, and ketoconazole and abiraterone that inhibit 17‑α-hydroxylase activity and thereby inhibit adrenal and testicular androgen steroidogenesis; 5‑α-reductase inhibitors that block conversion of testosterone to DHT and AR antagonists including enzalutamide that interfere with androgen binding to ARs and thereby inhibit AR signalling. Importantly, abiraterone is also able to block intratumoural synthesis of androgens in prostate cancer cells. DHEA, dehydroepiandrosterone; FSH, follicle-stimulating hormone.
Narayanan, S. et al. (2015) Androgen–glucocorticoid interactions in the era of novel prostate cancer therapy
Nat. Rev. Urol. doi: /nrurol