ESA-SRB-AOTA 2019

Androgen receptor signalling in the female adrenal cortex is dispensable for X-zone regression but protects against early onset spindle cell development (#508)

Anne-Louise Gannon 1 2 , Laura O'Hara 2 3 , J. Ian Mason 2 , Laura Milne 2 , Sarah E Smith 2 , Rod T Mitchell 2 , Lee B Smith 1 2
  1. The University of Newcastle, Callaghan, NSW, Australia
  2. CRH, The University of Edinburgh, Edinburgh, Scotland
  3. Centre for Discovery Brain Sciences, The University of Edinburgh, Edinburgh, Scotland

Androgens have been shown to be integral during ovarian folliculogenesis, embryonic implantation and uterine and breast development 1. Adrenal androgens are essential for these processes; however, the focus of adrenal androgen research is centred on disruption to production of androgens from the adrenal with little research investigating the role of androgen receptor (AR) signalling in the adrenal. This could be in part due to the perceived lack of suitable rodent model, as the mouse adrenal does not produce androgens due to methylation of Cyp17a1 during development 2. Despite this, studies in female mice show that androgens are able to influence the adrenal cortex.  The transient X-zone of the mouse adrenal cortex, thought to be a homologue for the human adrenal foetal zone, is essential for providing stem cells for the adult adrenal cortex. The X-zone regresses following pregnancy, however, studies have shown that the X-zone regresses following treatment with testosterone in virgin mice 3. Furthermore, loss of circulating androgens through gonadectomy results in a resurgence of the X-zone and development of adrenocortical tumours 4. The mechanism by which androgens regulate these processes and the adrenal cortex remains largely unknown.

To dissect the role of AR-signalling in the female mouse adrenal, we utilised a Cyp11a1-Cre that permits tissue-specific ablation of AR from the adrenal cortex.

Results demonstrate AR is dispensable for the postnatal developing female adrenal and surprisingly during X-zone regression following pregnancy. However, following disruption to adrenal AR, elevated serum corticosterone is observed in postpartum females and development of spindle cell hyperplasia in young adult females that progress with age.

These results point to potentially undefined roles for adrenal AR in postpartum-stress regulation. Furthermore, dysfunctional adrenal androgen signalling could be a possible mechanism in the development of adrenal spindle cell hyperplasia and could act as a potential therapeutic target.

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