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Title: DNA-binding-dependent androgen receptor signaling contributes to gender differences and has physiological actions in males and females.
Austin Authors: MacLean, Helen E;Moore, Alison J;Sastra, Stephen A;Morris, Howard A;Ghasem-Zadeh, Ali ;Rana, Kesha;Axell, Anna-Maree;Notini, Amanda J;Handelsman, David J;Seeman, Ego ;Zajac, Jeffrey D ;Davey, Rachel A
Affiliation: Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: 15-Apr-2010
Publication information: The Journal of Endocrinology 2010; 206(1): 93-103
Abstract: We used our genomic androgen receptor (AR) knockout (ARKO) mouse model, in which the AR is unable to bind DNA to: 1) document gender differences between males and females; 2) identify the genomic (DNA-binding-dependent) AR-mediated actions in males; 3) determine the contribution of genomic AR-mediated actions to these gender differences; and 4) identify physiological genomic AR-mediated actions in females. At 9 weeks of age, control males had higher body, heart and kidney mass, lower spleen mass, and longer and larger bones compared to control females. Compared to control males, ARKO males had lower body and kidney mass, higher splenic mass, and reductions in cortical and trabecular bone. Deletion of the AR in ARKO males abolished the gender differences in heart and cortical bone. Compared with control females, ARKO females had normal body weight, but 14% lower heart mass and heart weight/body weight ratio. Relative kidney mass was also reduced, and relative spleen mass was increased. ARKO females had a significant reduction in cortical bone growth and changes in trabecular architecture, although with no net change in trabecular bone volume. In conclusion, we have shown that androgens acting via the genomic AR signaling pathway mediate, at least in part, the gender differences in body mass, heart, kidney, spleen, and bone, and play a physiological role in the regulation of cardiac, kidney and splenic size, cortical bone growth, and trabecular bone architecture in females.
Gov't Doc #: 20395380
DOI: 10.1677/JOE-10-0026
Journal: The Journal of Endocrinology
Type: Journal Article
Subjects: Androgens.physiology
Body Weight
Bone Development
Bone and Bones.anatomy & histology
Calcification, Physiologic
Heart.anatomy & histology
Kidney.anatomy & histology
Mice, Inbred C57BL
Mice, Knockout
Organ Size
Receptors, Androgen.deficiency.physiology
Sex Characteristics
Signal Transduction.physiology
Spleen.anatomy & histology
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