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

Yonsei Med J. 2017 Nov;58(6):1204-1210. doi: 10.3349/ymj.2017.58.6.1204.

Abstract

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.

Keywords: 11β-hydroxysteroid dehydrogenase type 1; dermal papilla cells; glucocorticoids.

MeSH terms

  • 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

Substances

  • Glucocorticoids
  • Vascular Endothelial Growth Factor A
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Hydrocortisone