Fig. 6. Proposed mechanism for the androgenic regulation of wound healing. DHT binds to the AR and the resulting ligand-activated AR represents an effector complex whose activities may be modulated by Smad3. Activated AR stimulates macrophage production of pro-inflammatory cytokines, while at the same time depressing fibroblast cytokine expression and secretion. The increase in macrophage cytokine release, which depends on MAPK and PI 3-kinase signalling, contributes to enhanced inflammation and hence delayed healing.