Ultraviolet radiation regulates cortisol activity in a waveband-dependent manner in human skin ex vivo.
BACKGROUND
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), and glucocorticoids (GC) and their receptor (GR) play a key role in tissue-specific regulation of GC action.


OBJECTIVE
To determine the expression of genes encoding 11β-HSD1 (HSD11B1), 11β-HSD2 (HSD11B2) and GR (GRα; also known as NC3R1) and their protein products, and levels of cortisol in human skin explants and/or cocultured keratinocytes/melanocytes after treatment with ultraviolet (UV) A, B or C wavebands.


METHODS
Skin from foreskins and/or cocultured human keratinocytes/melanocytes were irradiated with UVA, UVB or UVC (skin) and incubated for 12 and 24 h. Methods of reverse transcription-polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay and immunohistochemistry (IHC) were used to determine expression and localization of corresponding genes or antigens.


RESULTS
UVB enhanced the HSD11B1 gene and protein expression in a dose-dependent manner, while UVA had no effect. Similarly, UVC increased 11β-HSD1 protein product as measured by IHC. UVB and UVC enhanced cortisol production and decreased epidermal GR expression, while UVA had no detectable effects. Although both UVA and UVB stimulated HSD11B2 gene expression, only UVA increased 11β-HSD2 protein product levels with UVB and UVC having no effect.


CONCLUSIONS
We suggest that these differential, waveband-dependent effects of UV radiation on the expression of cutaneous HSD11B1, HSD11B2 and GRα genes and their corresponding protein products, and cortisol production are to protect and/or restore the epidermal barrier homeostasis against disruption caused by the elevated cortisol level induced by UVB and UVC.
Department of Pathology and Laboratory Medicine, Center for Cancer Research, University of Tennessee, Health Science Center, Memphis, TN 38163, USA.
C
C
Skobowiat
R M
RM
Sayre
J C
JC
Dowdy
A T
AT
Slominski
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics* / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005938:Glucocorticoids / Q000378:metabolism / Q000528:radiation effects; D006706:Homeostasis; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism* / Q000528:radiation effects; D015603:Keratinocytes / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D011829:Radiation Dosage; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D012867:Skin / Q000378:metabolism*; D014466:Ultraviolet Rays
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468386:HSD11B1 protein, human; C468387:HSD11B2 protein, human; D006854:Hydrocortisone