title: Local cortisol/corticosterone activation in skin physiology and pathology.
abstract: Cortisol and corticosterone are the endogenous glucocorticoids (GCs) in humans and rodents, respectively. Systemic GC is released through the hypothalamic-pituitary-adrenal (HPA) axis in response to various stressors. Over the last decade, extra-adrenal production/activation of cortisol/corticosterone has been reported in many tissues. The enzyme that catalyzes the conversion of hormonally inactive cortisone/11-dehydrocorticosterone (11-DHC) into active cortisol/corticosterone in cells is 11β-hydroxysteroid dehydrogenase (11β-HSD). The 11β-HSD1 isoform is predominantly a reductase, which catalyzes nicotinamide adenine dinucleotide phosphate hydrogen-dependent conversion of cortisone/11-DHC to cortisol/corticosterone, and is widely expressed and present at the highest levels in the liver, lungs, adipose tissues, ovaries, and central nervous system. The 11β-HSD2 isoform, which catalyzes nicotinamide adenine dinucleotide+-dependent inactivation of cortisol/corticosterone to cortisone/11-DHC, is highly expressed in distal nephrons, the colon, sweat glands, and the placenta. In healthy skin, 11β-HSD1 is expressed in the epidermis and in dermal fibroblasts. On the other hand, 11β-HSD2 is expressed in sweat glands but not in the epidermis. The role of 11β-HSD in skin physiology and pathology has been reported recently. In this review, we summarize the recently reported role of 11β-HSD in the skin, focusing on its function in cell proliferation, wound healing, inflammation, and aging.
authors.affiliation: Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Japan. Electronic address: mterao@derma.med.osaka-u.ac.jp.
authors.forename: Mika
authors.initials: M
authors.lastname: Terao
authors.affiliation: Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism; D000375:Aging; D000818:Animals; D002280:Basal Cell Carcinoma / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D049109:Cell Proliferation; D003345:Corticosterone / Q000031:analogs & derivatives / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006859:Hydrogen / Q000378:metabolism; D007249:Inflammation; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism; D012879:Skin Physiological Phenomena; D014018:Tissue Distribution; D014945:Wound Healing
chemical_list: D006859:Hydrogen; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C003552:11-dehydrocorticosterone; D003345:Corticosterone; D006854:Hydrocortisone
keywords: 11β-hydroxysteroid; Corticosterone; Cortisol; Cortisone; Dehydrogenase; Keratinocyte; Skin