Dihydrotestosterone (DHT) Enhances Wound Healing of Major Burn Injury by Accelerating Resolution of Inflammation in Mice

Abstract

Androgens have been known to inhibit cutaneous wound healing in men and male mice. However, in children with major burn injuries, a synthetic androgen was reported clinically to improve wound healing. The aim of this study is to investigate the role of dihydrotestosterone (DHT) as a new therapeutic approach in treating major burn injury. In the present study, mice received systemic androgen treatment post major burn injury. Wound healing rate and body weight were monitored over 21 days. The serum level of inflammatory cytokines/chemokines were measured using multiplex immunoassays. In addition, splenocyte enumeration was performed by flow cytometry. Healing phases of inflammation, re-epithelialization, cell proliferation and collagen deposition were also examined. In results, DHT treated mice lost less weight and displayed accelerated wound healing but has no impact on hypermetabolism. Mice, after burn injury, displayed acute systemic inflammatory responses over 21 days. DHT treatment shortened the systemic inflammatory response with reduced splenic weight and monocyte numbers on day 14 and 21. DHT treatment also reduced wound infiltrating macrophage numbers. In conclusion, DHT treatment facilitates local wound healing by accelerating the resolution of inflammation, but not through alterations of post-burn hypermetabolic response.

Milk and Egg Are Risk Factors for Adverse Effects of Capecitabine-Based Chemotherapy in Chinese Colorectal Cancer Patients

“…Both DHT and its precursor cholesterol have pro-inflammatory effect. 41 , 42 Therefore, our results suggest that, as the overall inflammation is suppressed in patients susceptible to HFS, patients with a high risk of developing grade 2 or even more severe HFS may benefit from reducing the everyday milk consumption below 95 ml.…”

Controlled dual release of dihydrotestosterone and flutamide from polycaprolactone electrospun scaffolds accelerate burn wound healing

“…8,9 However, in contrast, the more potent, pure non-aromatizable androgen dihydrotestosterone (DHT) when administered systemically improved burn wound healing with earlier cell proliferation and collagen deposition. 10 These novel findings point to a previously unrecognized, paradoxical, and context-dependent role of androgens in wound healing that differs between burn and cutaneous injuries. The paradoxical, beneficial effects of systemic pure androgen administration on local wound healing raise the question of whether androgen receptor (AR)-mediated androgen actions may have an overlooked positive effect in local cutaneous healing of burn injury.…”

“…Rodent models have established that aromatize androgens like testosterone inhibit and prolong cutaneous wound healing in male mice, 4–7 an effect reversed by treatment with topical flutamide, an androgen antagonist 8,9 . However, in contrast, the more potent, pure non‐aromatizable androgen dihydrotestosterone (DHT) when administered systemically improved burn wound healing with earlier cell proliferation and collagen deposition 10 …”

The contradictory role of androgens in cutaneous and major burn wound healing

“…Aside from a few studies showing the effect of DHT treatment on increasing mouse skeletal muscle size and strength, research on the application of DHT in burn injury wound healing are limited [ 90 , 91 ]. In our recent study, the effect of DHT treatment in major burn injury healing was examined in a burn injury mouse model [ 92 , 93 ]. Our data showed that DHT has a positive impact on both local wound healing and metabolic catabolic responses, which differs from results reported after cutaneous injury.…”

“…The increase in monocyte chemoattractant protein-1 (MCP-1) level at the wound area and systemically recruits more monocytes to the blood circulation and the wound site. These monocytes were found to differentiate to macrophages, which are involved in removing bacteria, preventing infection and contributing to collagen disposition once the inflammation is resolved [ 93 ] ( Figure 5 ). Therefore, as a safer, non-hepatoxic androgen, DHT was approved for the first time to induce acceleration of the inflammatory turnover both locally and systemically as the key in promoting major burn injury wound healing without any adverse effects.…”