Endocrine Abstracts

Introduction: Androgens have long been known to play an important role in health and wellbeing. A range of clinical disorders in males and females can arise due to disruption to production and action of androgens. Androgen receptor (AR) is widely expressed throughout the adrenal cortex, yet the wider role for androgen signalling in the adrenal remains underexplored due to the lack of suitable animal models.

Methods: An adrenal-specific androgen receptor knockout mouse model was created by targeting GFP-Cre-GC to the mouse Cyp11a1 locus to drive Cre Recombinase expression in steroidogenic cells. Males were then mated to C57BL/6 female homozygous AR^fl/fl mice. C57BL/6 mice were also used to investigate normal adrenal function. Tissue was analysed through qRT-PCR and statistical analysis by one way ANOVA. Immunohistochemistry was used to determine changes in protein localisation.

Results: Results highlight that androgens signalling through AR is essential for the regression of the foetal ‘X-zone’ during puberty in male mice. Loss of androgens (through castration) or AR results in significant morphological differences in the adrenal cortex and X-Zone cells. However, interestingly, loss of androgens or AR impact cortex structure, gene expression and protein localisation differently.

Conclusions: We show that androgen signalling through AR is essential for removal of X-zone cells during puberty. We also demonstrate that androgens can act independently of AR to modulate cortex function. Additionally, the loss of androgen signalling results in a decrease in apoptotic cells, suggesting the adrenal has become more resistant to cell death. Improper removal of cortical cells and loss of apoptosis could have serious implications for adrenal function and disease progression. The impacts of this are undergoing further investigation.