ReviewRegulation of zonation and homeostasis in the adrenal cortex

- The adrenal cortex contains concentric zones without anatomical barriers.
- The different zones are distinguishable by morphology and steroidogenic activity.
- Wnt/β-catenin and ACTH/cAMP signaling pathways are essential for zonation.
- The capsule contains progenitor cells with limited activity in adult maintenance.
- Direct zG/zF conversion represents the major mechanism of adult tissue maintenance.

The adult adrenal cortex is organized into concentric zones, each specialized to produce distinct steroid hormones. Cellular composition of the cortex is highly dynamic and subject to diverse signaling controls. Cortical homeostasis and regeneration rely on centripetal migration of steroidogenic cells from the outer to the inner cortex, which is accompanied by direct conversion of zona glomerulosa (zG) into zona fasciculata (zF) cells. Given the important impact of tissue structure and growth on steroidogenic function, it is essential to understand the mechanisms governing adrenal zonation and homeostasis. Towards this end, we review the distinctions between each zone by highlighting their morphological and ultra-structural features, discuss key signaling pathways influencing zonal identity, and evaluate current evidence for long-term self-renewing stem cells in the adult cortex. Finally, we review data supporting zG-to-zF transdifferentiation/direct conversion as a major mechanism of adult cortical renewal.