UVB induces epidermal 11β‐hydroxysteroid dehydrogenase type 1 activity in vivo

Detrimental consequences of ultraviolet radiation (UVR) in skin include photoageing, immunosuppression and photocarcinogenesis, processes also significantly regulated by local glucocorticoid (GC) availability. In man, the enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) generates the active GC cortisol from cortisone (or corticosterone from 11‐dehydrocorticosterone in rodents). 11β‐HSD1 oxo‐reductase activity requires the cofactor NADPH, generated by hexose‐6‐phosphate dehydrogenase. We previously demonstrated increased 11β‐HSD1 levels in skin obtained from photoexposed versus photoprotected anatomical regions. However, the direct effect of UVR on 11β‐HSD1 expression remains to be elucidated. To investigate the cutaneous regulation of 11β‐HSD1 following UVR in vivo, the dorsal skin of female SKH1 mice was irradiated with 50, 100, 200 and 400 mJ/cm² UVB. Measurement of transepidermal water loss, 11β‐HSD1 activity, mRNA/protein expression and histological studies was taken at 1, 3 and 7 days postexposure. 11β‐HSD1 and hexose‐6‐phosphate dehydrogenase mRNA expression peaked 1 day postexposure to 400 mJ/cm² UVB before subsequently declining (days 3 and 7). Corresponding increases in 11β‐HSD1 protein and enzyme activity were observed 3 days postexposure coinciding with reduced GC receptor mRNA expression. Immunofluorescence studies revealed 11β‐HSD1 localization to hyperproliferative epidermal keratinocytes in UVB‐exposed skin. 11β‐HSD1 expression and activity were also induced by 200 and 100 (but not 50) mJ/cm² UVB and correlated with increased transepidermal water loss (indicative of barrier disruption). UVB‐induced 11β‐HSD1 activation represents a novel mechanism that may contribute to the regulation of cutaneous responses to UVR exposure.