Supraphysiological testosterone supplementation improves granulation tissue maturation through angiogenesis in the early phase of a cutaneous wound healing model in rats

Objective The aim of this study was to evaluate the effects of both testosterone depletion and supraphysiological testosterone supplementation in the early phase of an animal cutaneous wound healing model in comparison with the physiological hormonal condition. Material and Methods Forty rats were distributed into the following four groups: Control, Orchiectomy (OCX), Durateston (Dura) and OCX+Dura. On day 1, the testicles were removed (OCX group) and the rats (Dura group) received a supraphysiological dose (250 mg/kg) of exogenous testosterone weekly. After 15 days a full-thickness excisional skin wound was created in all animals, which was healed by the second intention for 7 days. On day 22, the rats were euthanatized and the wounds were harvested for histopathological evaluation, immunohistochemistry analyses and multiplex immunoassay . One-way ANOVA and post-hoc Tukey tests were performed. Results It was found that the supraphysiological testosterone level increased extracellular matrix deposition, promoted higher blood vessel formation and reduced wound contraction ( p < 0.05). Additionally, it also stimulated PCNA -positive fibroblasts and KGF -positive cells (p < 0.05), while orchiectomy reduced the expression of IL-6 and TNF-α and increased VEGF and PDGF ( p < 0.05) . Conclusion In conclusion, the results provide evidence that supraphysiological testosterone supplementation plays a positive role in the early phase of cutaneous wound healing, thus improving granulation tissue maturation through the enhancement of angiogenesis.