Rosacea is a chronic inflammatory disorder usually affecting the central face. Chronic use of topical steroids on the face causes lesions similar to rosacea. Synthesis and function of glucocorticoid (GC) have been established in healthy skin and various cutaneous diseases but not in rosacea. In most skin disorders, increased inflammation is usually coupled with a decline in the production of cutaneous GC. We designed this study to investigate the de novo GC synthesis in the skin and GC receptor expression in the lesional and the nonlesional skin of patients with erythematotelangiectatic rosacea (ETR). Both lesional and non-lesional facial skin samples from the same individuals were provided by twelve volunteers with rosacea (mean age, 40.1 years; range, 30 to 55 years). The key steroidogenic enzymes, CYP11A1, 3βHSD2 and CYP21A2, were significantly increased in the lesional skin at the gene and protein levels. CYP17A1 and steroidogenic acute regulatory protein (StAR) tended to be higher in the lesional skin. GC receptor was also significantly increased in the lesional skin. Progesterone was found to be increased significantly in the lesional skin using liquid chromatography-mass spectrometry Simultaneously, p65/p50 subunits of nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) and matrix metalloproteinases (MMP) gene expressions were significantly increased in the lesional skin. Also, p65 and p105 protein levels were significantly increased. These concurrent increments demonstrate that crosstalk between GC receptor and NFκB may be hampered in the lesional skin of ETR and may contribute to rosacea pathogenesis. We demonstrate that ETR is an inherently inflammatory disorder mediated by NFκB and that GC synthesis and GC receptor expression is increased in the lesional skin of ETR unlike in other cutaneous inflammatory diseases.

The role of abnormal cutaneous steroidogenesis in the pathogenesis of rosacea