Endocrine Abstracts

The human adrenal cortex can be divided into distinct zones that have both morphologic and biochemical differences. The production of aldosterone in the zona glomerulosa can be traced to the zone-specific expression of the enzymes involved in steroid biosynthesis. This is particularly true for its expression of the enzyme aldosterone synthase (CYP11B2). For aldosterone biosynthesis, CYP11B2 expression has often been called the ‘late rate-limiting’ step. We and others have shown that the expression of CYP11B2 is controlled at the level of its gene transcription, which is normally under tight control of the renin angiotensin system (RAS). Detailed analysis of the mechanisms regulating transcription of CYP11B2 has demonstrated a key role for the NGFI-B and the CREB/ATF families of transcription factors. In addition, we have extended the molecular studies to human disease and have shown that the recently described mutations in KCNJ5 increase adrenal cell expression of both CYP11B2 and NURR1. Thus, APA expression of KCNJ5 somatic mutations leads to renin-independent aldosterone production. A disruption in the normal regulation of NURR1 and CYP11B2 expression appears to be an important part of the disease process leading to primary aldosteronism. The ongoing studies are providing a detailed understanding of the molecular mechanisms regulating aldosterone and cortisol production within the normal adrenal and should provide insight into diseases of adrenal steroid excess.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.