Androgen Receptor in the adrenal cortex is essential for X-zone regression and to protect against spindle cell hyperplasia.
Androgens are known to be an essential regulator of male health. Androgen receptor (AR) is widely expressed throughout the adrenal cortex, yet the wider role for androgen signalling in the adrenal had until recently, remained undefined. Understanding how the adrenal regulates its cortex zones is essential for understanding adrenal steroid production and disease development when this production goes wrong.
To investigate AR-dependent and AR-independent androgen signalling in the adrenal, we used a novel mouse model with a specific ablation of androgen receptor in the adrenal cortex with or without reduction of circulating androgen levels by castration. Our results describe AR expression in the human and mouse adrenal and highlight that the mouse is a viable model to investigate androgen signalling in the adrenal cortex with human relevance. We show androgen signalling via AR is required for X-zone regression during puberty, an essential cortex zone that provides the necessary stem cells for the adult adrenal. Furthermore, cortex measurements define differences in X-zone morphology depending on whether circulating androgens or AR have been removed. We show androgens promote both cortical cell differentiation and apoptosis. Additionally, investigation of aged mice with AR ablation reveals severe cortex disruption, spindle cell hyperplasia and X-zone expansion. The data generated through this study demonstrates AR-signalling is required to facilitate X-zone regression, cell clearance and to protect against adrenal degeneration during ageing.
These findings are an exciting and significant step forward in understanding adrenal regulation and cortex differentiation. Due to the complex nature of adrenal regulation, new and novel models need to be developed and investigated to drive our current understanding of adrenal biology forward. This is essential for the development of much needed treatments for adrenal disease
Link to open access article https://www.nature.com/articles/s41598-019-46049-3