Journal article

Androgens stimulate erythropoiesis through the DNA-binding activity of the androgen receptor in non-hematopoietic cells

Julie F McManus, Nhu-Y N Nguyen, Rachel A Davey, Helen E MacLean, Giovanna Pomilio, Matthew P McCormack, Wan Sze Chiu, Andrew H Wei, Jeffrey D Zajac, David J Curtis

European Journal Of Haematology | WILEY | Published : 2020


BACKGROUND: Androgens function through DNA and non-DNA binding-dependant signalling of the androgen receptor (AR). How androgens promote erythropoiesis is not fully understood. DESIGN AND METHODS: To identify the androgen signalling pathway, we treated male mice lacking the second zinc finger of the DNA binding domain of the AR (AR∆ZF2 ) with non-aromatizable 5α-dihydrotestosterone (5α-DHT), or aromatizable testosterone. To distinguish direct hematopoietic and non-hematopoietic mechanisms we performed bone marrow reconstitution experiments. RESULTS: In wild-type mice, 5α-DHT had greater erythroid activity than testosterone, which can be aromatized to estradiol. The erythroid response in wild..

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Funding Acknowledgements

National Health and Medical Research Council; Medical Research Future Fund; The Eva and Les Erdi Major Research Grants; Sir Edward Dunlop Medical Research Foundation Grants; The Austin Medical Research Fund; Leukaemia Foundation; Merck & Co.; Australian Cancer Research Foundation; The University of Melbourne MRGS