Increased glucocorticoid activation during mouse skin wound healing

J Endocrinol. 2014 Mar 7;221(1):51-61. doi: 10.1530/JOE-13-0420. Print 2014 Apr.


Glucocorticoid (GC) excess inhibits wound healing causing increased patient discomfort and infection risk. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activates GCs (converting 11-dehydrocorticosterone to corticosterone in rodents) in many tissues including skin, where de novo steroidogenesis from cholesterol has also been reported. To examine the regulation of 11β-HSD1 and steroidogenic enzyme expression during wound healing, 5 mm wounds were generated in female SKH1 mice and compared at days 0, 2, 4, 8, 14, and 21 relative to unwounded skin. 11β-HSD1 expression (mRNA and protein) and enzyme activity were elevated at 2 and 4 days post-wounding, with 11β-HSD1 localizing to infiltrating inflammatory cells. 11β-HSD2 (GC-deactivating) mRNA expression and activity were undetectable. Although several steroidogenic enzymes displayed variable expression during healing, expression of the final enzyme required for the conversion of 11-deoxycorticosterone to corticosterone, 11β-hydroxylase (CYP11B1), was lacking in unwounded skin and post-wounding. Consequently, 11-deoxycorticosterone was the principal progesterone metabolite in mouse skin before and after wounding. Our findings demonstrate that 11β-HSD1 activates considerably more corticosterone than is generated de novo from progesterone in mouse skin and drives GC exposure during healing, demonstrating the basis for 11β-HSD1 inhibitors to accelerate wound repair.

Keywords: 11β-hydroxysteroid dehydrogenase; glucocorticoid; skin; steroidogenesis; wound healing.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / genetics
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / metabolism
  • Animals
  • Female
  • Glucocorticoids / metabolism*
  • Humans
  • Mice
  • Mice, Hairless
  • Receptors, Glucocorticoid / metabolism
  • Skin / enzymology
  • Skin Physiological Phenomena*
  • Wound Healing*


  • Glucocorticoids
  • Receptors, Glucocorticoid
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2