Intracrine androgen synthesis enzyme

Intracrine androgen synthesis enzymes are a collection of enzymes responsible for converting circulating androgen precursors, primarily dehydroepiandrosterone (DHEA) and androstenedione, into active androgens (testosterone, dihydrotestosterone, and 11-ketotestosterone) within peripheral tissues, without significant release into the circulation. These enzymes include cytochrome P450 enzymes (such as CYP17A1), hydroxysteroid dehydrogenases (such as AKR1C3/17βHSD5, HSD3B1, HSD17B2), and steroid 5α-reductases (SRD5A1, SRD5A2), among others. The activity of these enzymes enables tissues like the prostate, skin, and certain tumors to sustain local androgen action, and is a key mechanism of resistance in androgen deprivation therapy for prostate cancer[1][2][3][5][7][8]. Their dysregulated expression is implicated in the progression of several hormone-dependent diseases and cancers, making them targets for therapeutic inhibition. Because “Intracrine androgen synthesis enzymes” refers to a functionally related group, a more structured approach would catalog each enzyme (e.g., “Aldo-keto reductase family 1 member C3 (AKR1C3)”) as individual targets.

Other names

Intracrine androgen biosynthesis enzymesSteroidogenic enzymes (when referring to androgens)Local androgen synthesis enzymesKey individual enzymes: AKR1C3 (17β-hydroxysteroid dehydrogenase type 5)CYP17A1 (17α-hydroxylase/17,20-lyase)HSD3B1SRD5A1/2 (steroid 5α-reductases)AKR1C1AKR1C2HSD17B2HSD17B4

Inhibition of androgen synthesis (e.g., CYP17A1 inhibitors reduce testosterone production in tumors); Decreasing intratumoral androgen availability; Inhibiting local androgen conversion from precursors; Augmenting androgen inactivation (targeting inactivating enzymes such as AKR1C1/C2).