title: Localization, age- and site-dependent expression, and regulation of 11β-hydroxysteroid dehydrogenase type 1 in skin.
abstract: Glucocorticoids (GCs) are highly detrimental to skin integrity and function both when applied topically for anti-inflammatory treatments and during conditions of circulating excess, e.g., Cushing's syndrome. Within target tissues, GC availability is regulated at a prereceptor level, independently of systemic levels, by isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) that interconvert active cortisol and inactive cortisone. Many of the adverse effects of GCs on skin are also reminiscent of the natural aging process. 11β-HSD1 (which activates cortisol), but not 11β-HSD2 (which inactivates cortisol), was expressed in epidermal keratinocytes and dermal fibroblasts in human skin and also in outer hair follicle root sheath cells in murine skin. 11β-HSD1 activity was present ex vivo in both species and increased with age in human skin tissue explants. In primary human dermal fibroblasts (HDF) from both photoprotected and photoexposed sites, 11β-HSD1 also increased with donor age. Additionally, photoexposed HDF displayed higher 11β-HSD1 mRNA expression than donor-matched photoprotected HDF. GC treatment of HDF caused upregulation of 11β-HSD1 mRNA levels independent of donor age or site. The age- and site-associated increase in dermal 11β-HSD1, and the ensuing increased local GC activation, may contribute to the adverse changes in skin morphology and function associated with chronological aging and photoaging.
authors.affiliation: Centre for Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Tiganescu
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Walker
authors.forename: Rowan S
authors.initials: RS
authors.lastname: Hardy
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Mayes
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000276:immunology; D000818:Animals; D002237:Carbohydrate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D020405:Dermis / Q000201:enzymology / Q000276:immunology; D004817:Epidermis / Q000201:enzymology* / Q000276:immunology; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D005938:Glucocorticoids / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D015595:Skin Aging / Q000276:immunology*
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; D002237:Carbohydrate Dehydrogenases; C020552:galactose-6-phosphate dehydrogenase; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human