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11β-Hydroxysteroid Dehydrogenase Type 1 Inhibition Attenuates the Adverse Effects of Glucocorticoids on Dermal Papilla Cells.

 Sang Eun Lee  ;  Eun Young Lee  ;  Sang Jin Kang  ;  Seung Hun Lee 
 YONSEI MEDICAL JOURNAL, Vol.58(6) : 1204-1210, 2017 
Journal Title
Issue Date
11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & inhibitors* ; 11-beta-Hydroxysteroid Dehydrogenase Type 1/genetics ; Blotting, Western ; Cell Proliferation/drug effects* ; Cells, Cultured ; Fibroblasts/metabolism* ; Glucocorticoids/pharmacology* ; Humans ; Hydrocortisone ; Keratinocytes/metabolism* ; Signal Transduction ; Vascular Endothelial Growth Factor A
11β-hydroxysteroid dehydrogenase type 1 ; dermal papilla cells ; glucocorticoids
PURPOSE: Glucocorticoids, stress-related hormones, inhibit hair growth. Intracellular glucocorticoid availability is regulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). 11β-HSD1 was recently detected in keratinocytes and fibroblasts. However, the expression of 11β-HSD1 in human hair follicles remains unknown. We aimed to examine 11β-HSD1 expression in human dermal papilla cells (DPCs) and to investigate whether modulation of 11β-HSD1 activity can regulate the negative effects of glucocorticoids on DPCs. MATERIALS AND METHODS: 11β-HSD1 expression in normal human scalp skin was examined by immunohistochemistry. 11β-HSD1 protein was detected in Western blots of human DPCs. Cultured human DPCs were treated with cortisol with or without a selective 11β-HSD1 inhibitor and subsequently stained for Ki-67 antibody. Expression levels of 11β-HSD1, Wnt5a, alkaline phosphatase (ALP), and vascular endothelial growth factor (VEGF) were analyzed by Western blotting. RESULTS: 11β-HSD1 was detected in dermal papilla in human scalp skin by immunohistochemistry. Human DPCs expressed 11β-HSD1 protein in vitro. Furthermore, cortisol stimulated the expression of 11β-HSD1 in DPCs. Glucocorticoids decreased cellular proliferation and the expression of Wnt5a, ALP, and VEGF in DPCs. A specific 11β-HSD1 inhibitor significantly attenuated the anti-proliferative effects of cortisol and reversed the cortisol-induced suppression of Wnt5a, ALP, and VEGF expression in DPCs. CONCLUSION: Our data demonstrated the expression of 11β-HSD1 in human DPCs and revealed that inhibition of 11β-HSD1 activity can partially prevent the negative effect of glucocorticoids on DPCs, suggesting the possible application of 11β-HSD1 inhibitors for stress-related hair loss.
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1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Sang Eun(이상은) ORCID logo https://orcid.org/0000-0003-4720-9955
Lee, Seung Hun(이승헌)
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