Role of corticosteroids in skin physiology and therapeutic potential of an 11β-HSD1 inhibitor: A review

Skin is a major site of cortisol bioconversion by 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) enzymes which catalyze intracellular inactive cortisone into physiologically active cortisol. 11 beta-HSD1 is highly expressed in skin, especially in dermal fibroblasts, epidermal keratinocytes, melanocytes, and hair follicles, and plays important roles in regulating keratinocytes, fibroblast proliferation, and has roles in skin aging. Inhibition of 11 beta-HSD1 may reverse decreased collagen levels observed in extrinsically and intrinsically aged skin. Inhibitors of 11 beta-HSD1 may also have the potential to reverse decreased collagen observed in skin atrophy induced by glucocorticoid treatment. This systematic review aimed to summarize the current knowledge of roles for 11 beta-HSD1 inhibitor in skin physiology and potential for future use in medications. Studies have demonstrated that immediately following experimental insult in an animal model, there is increased expression of 11 beta-HSD1, and that topical application of an 11 beta-HSD1 inhibitor increases the rate of healing, increases skin collagen content, increases dermal fibroblasts, and increases dermal thickness. Furthermore, in patients with type 2 diabetes mellitus, 11 beta-HSD1 inhibitors reduce wound diameter after injury. Further development of 11 beta-HSD1 inhibitors appears to be a promising area for treating aging skin, aiding wound healing, and mitigating effects of systemic glucocorticoid use. Both topically and orally administered 11 beta-HSD1 inhibitors appear to be viable avenues for future research.