Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/23028
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dc.contributor.authorMcManus, Julie F-
dc.contributor.authorNguyen, Nhu-Y N-
dc.contributor.authorDavey, Rachel A-
dc.contributor.authorMacLean, Helen E-
dc.contributor.authorPomilio, Giovanna-
dc.contributor.authorMcCormack, Matthew P-
dc.contributor.authorChiu, Wan Sze-
dc.contributor.authorWei, Andrew H-
dc.contributor.authorZajac, Jeffrey D-
dc.contributor.authorCurtis, David J-
dc.date2020-04-20-
dc.date.accessioned2020-04-23T04:23:47Z-
dc.date.available2020-04-23T04:23:47Z-
dc.date.issued2020-09-
dc.identifier.citationEuropean Journal of Haematology 2020; 105(3): 247-254en_US
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/23028-
dc.description.abstractAndrogens function through DNA and non-DNA binding-dependant signalling of the androgen receptor (AR). How androgens promote erythropoiesis is not fully understood. 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. In wild-type mice, 5α-DHT had greater erythroid activity than testosterone, which can be aromatized to estradiol. The erythroid response in wild-type mice following 5α-DHT treatment was associated with increased serum erythropoietin (EPO) and its downstream target erythroferrone, and hepcidin suppression. 5α-DHT had no erythroid activity in AR∆ZF2 mice, proving the importance of DNA binding by the AR. Paradoxically testosterone, but not 5α-DHT, suppressed EPO levels in AR∆ZF2 mice, suggesting testosterone following aromatization may oppose the erythroid-stimulating effects of androgens. Female wild-type mice reconstituted with AR∆ZF2 bone marrow cells remained responsive to 5α-DHT. In contrast, AR∆ZF2 mice reconstituted with female wild-type bone marrow cells showed no response to 5α-DHT. Erythroid promoting effects of androgens are mediated through DNA binding-dependent actions of the AR in non-hematopoietic cells, including stimulating EPO expression.en_US
dc.language.isoeng-
dc.subjectDNA binding actionsen_US
dc.subjectandrogen receptor signallingen_US
dc.subjectandrogensen_US
dc.subjecterythropoiesisen_US
dc.subjecterythropoietinen_US
dc.subjectgenetically modified androgen receptor mouse modelen_US
dc.subjectnon-hematopoietic cellsen_US
dc.titleAndrogens stimulate erythropoiesis through the DNA binding activity of the androgen receptor in non-hematopoietic cells.en_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleEuropean Journal of Haematologyen_US
dc.identifier.affiliationHuman Molecular Pathology, Alfred Pathology Service, Alfred Health, Melbourne, Australiaen_US
dc.identifier.affiliationCartherics Pty Ltd, Melbourne, Australiaen_US
dc.identifier.affiliationHudson Institute of Medical Research, Melbourne, Australiaen_US
dc.identifier.affiliationAustralian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, Australiaen_US
dc.identifier.affiliationDepartment of Clinical Haematology, Alfred Health, Melbourne, Australiaen_US
dc.identifier.affiliationMedicine (University of Melbourne)en_US
dc.identifier.doi10.1111/ejh.13431en_US
dc.type.contentTexten_US
dc.identifier.orcid0000-0001-5121-0209en_US
dc.identifier.orcid0000-0003-3933-5708en_US
dc.identifier.pubmedid32311143-
dc.type.austinJournal Article-
local.name.researcherZajac, Jeffrey D
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptEndocrinology-
crisitem.author.deptMedicine (University of Melbourne)-
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