title: Stress-Induced Hormones Cortisol and Epinephrine Impair Wound Epithelization.
abstract: BACKGROUND
  Stress-induced disruption of hormonal balance in animals and humans has a detrimental effect on wound healing.
  
  
  OBJECTIVE
  After the injury, keratinocytes migrate over the wound bed to repair a wound. However, their nonmigratory phenotype plays a role in pathogenesis of chronic wounds. Despite many therapeutic approaches, there is a dearth of treatments targeting the molecular mechanisms mediated by stress that prevent epithelization.
  Recent studies show that epidermal keratinocytes synthesize stress hormones. During acute wound healing, cortisol synthesis in the epidermis is tightly controlled. Further, a key intermediate molecule in the cholesterol synthesis pathway, farnesyl pyrophosphate (FPP), can bind glucocorticoid receptor (GR) and activate GR. Additionally, keratinocytes express beta-2-adrenergic-receptor (β2AR), a receptor for the stress hormone epinephrine. Importantly, migratory rates of keratinocytes are reduced by cortisol, FPP, epinephrine, and other β2AR agonists, thus indicating their role in the inhibition of epithelization. Topical inhibition of local glucocorticoid and FPP synthesis, as well as treatment with β2AR antagonists promotes wound epithelization.
  Modulation of local stress hormone production may represent an important therapeutic target for wound healing disorders. Topical administration of inhibitors of cortisol synthesis, statins, β2AR antagonists, and systemic beta-blockers can decrease cortisol synthesis, FPP, and epinephrine levels, respectively, thus restoring keratinocyte migration capacity. These treatment modalities could represent a novel therapeutic approach for wound healing disorders.
  
  
  CONCLUSIONS
  Attenuation of the local stress-induced hormonal imbalance in epidermis may advance therapeutic modalities, thereby leading to enhanced epithelization and improved wound healing.
authors: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine , Miami, Florida.
authors: Olivera
authors: O
authors: Stojadinovic
authors: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine , Miami, Florida.
authors: Katherine A
authors: KA
authors: Gordon
authors: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine , Miami, Florida.
authors: Elizabeth
authors: E
authors: Lebrun
authors: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine , Miami, Florida.
authors: Marjana
authors: M
authors: Tomic-Canic