The actions of the male sex hormone, testosterone, to decrease fat mass.

Lead Researcher Email Number Webpage
Associate Professor Rachel Davey r.davey@unimelb.edu.au +61 3 9496 5507 Personal web page

Project Details

Obesity has been deemed a pandemic by the World Health Organisation with approximately 60% of Australian adults being overweight or obese, with childhood obesity rates also on the rise. Obesity is a major risk factor for the development of type II diabetes, cardiovascular disease, cancer and skeletal joint destruction as well as many other serious diseases.   As such, the increasing prevalence of this disease is of serious concern, especially since the current management and treatment of obesity are clearly inadequate. Therefore novel approaches to therapy are urgently required. The male sex steroid hormone, testosterone, decreases fat mass. The ways in which testosterone decreases fat mass however, are poorly understood. Importantly, testosterone cannot be used as a therapy for women, ageing men and prostate cancer patients undergoing androgen deprivation therapy due to potential side-effects.  The aim of our study is to understand precisely the way in which testosterone acts to decrease fat mass. Recently, it has been identified that bone, as an endocrine organ, can exert feedback regulation on aspects of energy metabolism via the secretion of osteokines As such, we wish to test whether testosterone acts via the androgen receptor in cells residing within the bone marrow to regulate the secretion of bone-derived factors (osteokines), which are then released into the circulation to negatively regulate fat mass.  This will be achieved by using an innovative genetically modified in vivo mouse model. Identification of the mechanism/s by which testosterone decreases fat mass will lead to new therapeutic targets for the treatment of obesity.

Researchers

Collaborators

Funding

  • Sir Edward Dunlop Medical Research Foundation, "Understanding the action of androgens to decrease fat mass."
  • Ian Potter Foundation, "Translation of bone biology research into better treatments for osteoporosis, cancer and arthritis."

Research Outcomes

Research Publications

  • Davey RA and Grossmann M. Androgen receptor structure, function and biology: From bench to bedside. The Clinical Biochemist Reviews, 2016, 37(1):3-15.
  • Russell PK, Clarke MV, Cheong K, Anderson PH, Morris HA, Wiren KM, Zajac JD, Davey RA.  Androgen receptor action in osteoblasts in male mice is dependent on their stage of maturation. Journal of Bone and Mineral Research, 2015, 30(5): 809-823.
  • Sinnesael M, Jardi F, Deboel L, Laurent MR, Dubois V, Zajac JD, Davey RA, Carmeliet G, Claessens F, Vanderschueren D. The androgen receptor has no direct antiresorptive actions in mouse osteoclasts. Molecular and Cellular Endocrinology, 2015, 411:198-206.
  • Russell PK, Clarke MV, Skinner JP, Pang TPS, Zajac JD, Davey RA. Identification of gene pathways altered by deletion of the androgen receptor specifically in mineralizing osteoblasts and osteocytes in mice. Journal of Molecular Endocrinology, 2012, 49(1): 1-10.
  • Davey RA, Clarke MV, Sastra S, Skinner JP, Chiang C, Anderson PH, Zajac JD. Decreased body weight in young Osterix-Cre transgenic mice results in delayed cortical bone expansion and accrual. Transgenic Research, 2012, 21(4):885-93.
  • Pang TPS, Clarke MV, Ghasem-Zadeh A, Lee NKL, Davey RA*, MacLean* (Equal senior authors). A physiological role for androgen actions in the absence of androgen receptor DNA binding activity. Molecular and Cellular Endocrinology, 2012, 348: 189-197.
  • MacLean HE, Moore AJ, Sastra SA, Morris HA, Ghasem-Zadeh A, Rana K, Axell AM, Notini AJ, Handelsman DJ, Seeman E, Zajac JD, Davey RA.  “DNA-binding-dependent androgen receptor signaling contributes to gender differences and has physiological actions in males and females”.  Journal of Endocrinology  2010, 206, 93-103.
  • Chiang C, Chiu MWS, Moore AJ, Ghasem-Zadeh A, McManus JF, Ma C, Doust EA, Seeman E, Clemens T, Morris HA, Zajac JD, Davey RA. Mineralization and Bone Resorption are Regulated by the Androgen Receptor in Male Mice. Journal of Bone and Mineral Research, 2009 24(4):621-31.
  • Notini AJ, McManus JF, Moore AJ, Bouxsein M, Jimenez M, Chiu WSM, Glatt V, Kream BE, Handelsman DJ, Morris HA, Zajac JD, Davey RA. Osteoblast-specific deletion of exon 3 of the androgen receptor gene results in trabecular bone loss in adult male mice. Journal of Bone and Mineral Research, 2007; 22(3):347-56.
  • Notini AJ, Davey RA, McManus JF, Bate KL, Zajac JD. Genomic actions of the androgen receptor are required for normal male sexual differentiation in a mouse model.  Journal of Molecular Endocrinology 2005; 35(3):547-55.

Research Group

Molecular Endocrinology and Musculoskeletal Research Group


School Research Themes

Musculoskeletal



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Medicine and Radiology

Unit / Centre

Molecular Endocrinology and Musculoskeletal Research Group