Androgen receptor signalling in the male adrenal facilitates X-zone regression, cell turnover and protects against adrenal degeneration during ageing.

Autor: Gannon AL; MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.; School of Environmental and Life Sciences, Faculty of Science, University of Newcastle, Callaghan, 2308, NSW, Australia., O'Hara L; MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.; Centre for Discovery Brain Sciences, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, UK., Mason JI; MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK., Jørgensen A; Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.; International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Copenhagen, Denmark., Frederiksen H; Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.; International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Copenhagen, Denmark., Milne L; MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.; Edinburgh Genome Foundry, Michael Swann Building, Max Bonn Crescent, Edinburgh, EH9 3BF, UK., Smith S; MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK., Mitchell RT; MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK., Smith LB; MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. Lee.Smith@ed.ac.uk.; School of Environmental and Life Sciences, Faculty of Science, University of Newcastle, Callaghan, 2308, NSW, Australia. Lee.Smith@ed.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Jul 18; Vol. 9 (1), pp. 10457. Date of Electronic Publication: 2019 Jul 18.
DOI: 10.1038/s41598-019-46049-3
Abstrakt: 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 remains underexplored. 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. We show androgen signalling via AR is required for X-zone regression during puberty. 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 but are dispensable for the formation of the definitive cortex. Additionally, investigation of aged mice with AR ablation reveals severe cortex disruption, spindle cell hyperplasia and X-zone expansion. The data described herein demonstrates AR-signalling is required to facilitate X-zone regression, cell clearance and to protect against adrenal degeneration during ageing.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje