1. Nat. Rev. Urol. doi:10.1038/nrurol.2015.254
Figure 2 Adrenal steroidogenic pathways in androgen synthesis: inhibition and consequences of abiraterone inhibition of 17α‑hydroxylase to block androgen and cortisol synthesis
Figure 2 | Adrenal steroidogenic pathways in androgen synthesis: inhibition and consequences of abiraterone inhibition of 17α‑hydroxylase to block androgen and cortisol synthesis. Abiraterone inhibits 17α‑hydroxylase (CYP17A), resulting in a loss of both 17‑hydroxylation and 17–20 lyase activity. This results in a blockade of both androgen and cortisol synthesis. Reduction in adrenal cortisol secretion leads to a loss of negative feedback to the pituitary (dashed arrow) resulting in an elevation of adrenocorticotropic hormone (ACTH) secretion. This elevated ACTH drives the mineralocorticoid synthesis pathway, which is the one steroidogenic pathway that does not require 17α‑hydroxylase activity. The elevated aldosterone precursors, deoxycorticosterone (DOC) and corticosterone, stimulate mineralocorticoid receptor (MR) signalling leading to increased blood volume, elevated blood pressure and potassium loss. These changes in turn suppress renin levels in the kidney and consequently aldosterone synthesis (shown by a dashed arrow). To counteract these negative effects, prednisone is usually co-administered with abiraterone to prevent glucocorticoid deficiency and suppress the elevated levels of ACTH, also alleviate the excess mineralocorticoid activity. Sometimes mineralocorticoid antagonists are added in order to achieve complete suppression of the adverse effects of elevations in DOC and corticosterone. 3βHSD2, 3β‑hydroxysteroid dehydrogenase 2; 17OH‑Preg, 17‑hydroxypregnenolone; 17OH‑Prog, 17‑hydroxyprogesterone; ACTH, adrenocorticotropic hormone; ANDRO, androstenedione; CYP17A, steroid 17α‑hydroxylase/17,20 lyase (also known as 17α‑hydroxylase); DHEA, dehydroepiandrosterone.
Narayanan, S. et al. (2015) Androgen–glucocorticoid interactions in the era of novel prostate cancer therapy
Nat. Rev. Urol. doi: /nrurol