A new dawn for androgens: Novel lessons from 11-oxygenated C19 steroids

Abstract

The abundant adrenal C19 steroid 11β-hydroxyandrostenedione (11OHA4) has been written off as a dead-end product of adrenal steroidogenesis. However, recent evidence has demonstrated that 11OHA4 is the precursor to the potent androgenic 11-oxygenated steroids, 11-ketotestosterone and 11-ketodihydrotestosterone, that bind and activate the human androgen receptor similarly to testosterone and DHT. The significance of this discovery becomes apparent when considering androgen dependent diseases such as castration resistant prostate cancer and diseases associated with androgen excess, e.g. congenital adrenal hyperplasia and polycystic ovary syndrome. In this review we describe the production and metabolism of 11-oxygenated steroids. We subsequently discuss their androgenic activity and highlight the putative role of these androgens in disease states.

Keywords: 11-Ketodihydrotestosterone (11KDHT); 11-Ketotestosterone (11KT); Adrenal androgens; Castration resistant prostate cancer (CRPC); Congenital adrenal hyperplasia (CAH); Polycystic ovary syndrome (PCOS).