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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.

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      Biography

      Mika Terao (M.D., Ph.D.) is Assistant Professor at Department of Regenerative Dermatology, Osaka University School of Medicine, Osaka, Japan. She received her MD degree from University of Tsukuba, Japan and her Ph.D. degree from Osaka University, Japan. She served several months of externship in University of Irvine, CA, USA. She has particular interest in dermatoendocrinology especially in the role of cortisol and vitamin D in the skin. She started to have an interest in local cortisol/corticosterone activating enzyme when she was Ph.D. student. Since then, she has generated knockout mice and investigating the role of this enzyme in vivo and the role in human skin diseases.