Intracrine Androgen Synthesis Enzymes

Intracrine androgen synthesis enzymes are a functional group of proteins that mediate the local production of potent androgens, such as testosterone and 5α-dihydrotestosterone (DHT), within peripheral tissues from inactive or weakly active precursors. This process, termed intracrinology, allows tissues like the prostate to maintain high androgenic activity even when systemic levels are low, such as during androgen deprivation therapy (ADT). Key enzymes in this pathway include CYP17A1, which produces adrenal precursors; 3β-hydroxysteroid dehydrogenase (HSD3B1), which converts dehydroepiandrosterone (DHEA) to androstenedione; aldo-keto reductase family 1 member C3 (AKR1C3), which converts androstenedione to testosterone; and 5α-reductases (SRD5A1 and SRD5A2), which convert testosterone to the more potent DHT. In castration-resistant prostate cancer (CRPC), these enzymes are frequently upregulated or mutated, providing a mechanism for tumor cells to bypass systemic castration and continue driving androgen receptor (AR) signaling. Therapeutic strategies targeting these enzymes, such as the use of abiraterone to inhibit CYP17A1 or finasteride and dutasteride to inhibit 5α-reductases, are central to the management of advanced prostate cancer and other androgen-dependent conditions.

Other names

Intratumoral androgen synthesis enzymesSteroidogenic enzymesPeripheral androgen synthesis enzymesIntracrine steroidogenic enzymes

Inhibition of steroidogenic enzymes to deplete the intratumoral pool of potent androgens and suppress androgen receptor-mediated signaling.