Endocrine Abstracts

UVB exposure induces skin damage including dermal atrophy, telangiectasia, fragility and poor wound healing; symptoms also attributable to glucocorticoid (GC) excess (e.g. Cushing’s syndrome). In peripheral tissues including skin, GC availability is regulated by 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1/2 which respectively activate/deactivate cortisol (and rodent corticosterone) from/to cortisone (and rodent 11-dehydrocorticosterone). Although we previously demonstrated increased 11β-HSD1 levels in photo-exposed vs photo-protected human skin, direct regulation of 11β-HSD1 expression by UVB in vivo remains unexplored.

We irradiated female SKH1-hr mice with 0, 50, 100, 200 and 400 mJ UVB/cm² and collected skin tissue at 0, 1, 3 and 7 days (d0 etc.) post-exposure. At 400 mJ, 11β-HSD1 mRNA expression (measured by qPCR normalized to 18S rRNA) increased 2.7-fold at d1 (^P<0.01), remaining high but more variable at subsequent timepoints. Hexose-6-phosphate dehydrogenase (11β-HSD1 cofactor-supplying enzyme) mRNA expression also increased 2.5-fold at d1 (P<0.05) returning to non-irradiated levels by d7. Conversely, GC receptor mRNA was 31% lower at d3 (P<0.05). 11β-HSD2 is not expressed in murine skin.

At 400 mJ, 11β-HSD1 activity (determined by incubation with 100 nM tritiated 11-dehydrocorticosterone) was 76% greater than d0 only at d3 (3.6 vs 2.1 pmol/h, P<0.05) and was also increased by 100 and 200 mJ (40%, P<0.05 and 50%, P<0.001 respectively). Localization studies (by immunofluorescence) revealed 11β-HSD1-positive staining in hyperproliferative epidermis vs non-irradiated skin at 100 and 200 mJ (81.2 and 77.4 vs 21.2 μm, P<0.001) with increased stain intensity but reduced hyperproliferation at 400 mJ (41 μm, P<0.001). Dermal 11β-HSD1 expression was unaffected by UVB exposure.

Our findings suggest increased 11β-HSD1 activity following UVB exposure in vivo may exacerbate UV-induced skin damage by increasing local GC availability. Topical 11β-HSD1 inhibitors may minimize adverse consequences of UVB exposure.