The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Dihydrotestosterone (DHT) enhances wound healing from severe burn injury through regulating inflammatory response (#154)

Huaikai Shi 1 , Brain Lesmana 1 , Brenton Condor 1 , Roxanne Parungao 1 , Tsun Ho Lo 2 , Pablo Silveira 2 , Sarah Kim 3 , Duncan Ma 1 , Kevin Tasi 1 , Ulla Simanainen 4 , Mark Cooper 5 , Peter Maitz 6 , David Handelsman 4 , Yiwei Wang 1
  1. Burns Research , Anzac Research Institute, Sydney, NSW, Australia
  2. Dendritic Cell Research, ANZAC Research Institute, Sydney, NSW, Australia
  3. Bone Biology , Anzac Research Insitute, Sydney, NSW, Australia
  4. Andrology , Anzac Research Institute, Sydney, NSW, Australia
  5. Adrenal Steroids, Anzac Research Institute , Sydney, NSW, Australia
  6. Burns Unit, Concord Hospital , Sydney, NSW, Australia

Rationale: In treatment of childhood burns, synthetic androgens are reported to better maintain lean body mass, with reduced hypermetabolic responses characteristic of severe burns injury and shortened healing time for severe burns injury. These findings are contrary to experimental evidence in rodents that androgens inhibit skin wound healing. The aim of this study therefore is to identify the role of androgens in complex severe burn injury, in particularly to determine the impact of androgens on local healing process and on systemic burns-induced hypermetabolic state.

Methods: A severe burn injury mouse model (40% TBSA, full thickness) was established featuring increased circulating corticosteroid, energy expenditure and lean body mass loss. Using this experimental model, mice underwent subdermal insertion of silastic implants containing the pure DHT or placebo and wound healing rate was observed over 21 days. Body weight, energy expenditure and circulating cytokines (Multiplex Immunoassay System) were measured. Spleen histology was analysed and immune cells enumerated by flow cytometry. Local wound healing process including inflammation, re-epithelialization, cell proliferation and collagen deposition were assessed using histology, immunohistochemistry and RT-PCR.

Results: DHT treatment significantly enhanced wound healing over 14 days with better maintained body weight, whereas DHT treatment had no effect on burn-induced hypermetabolism. In the control group, injured mice showed chronic inflammatory response with significantly increased number of splenic monocytes and wound macrophages at day 14. In comparison, DHT treatment accelerated inflammatory responses with early increase of circulating inflammatory cytokines and number of splenic monocytes as well as wound macrophages. Furthermore, DHT promoted cell proliferation and collagen deposition over wound healing process.

Conclusion: DHT accelerate wound healing by regulating inflammatory response but not through the hypermetabolism.