The aldo-keto reductase 1C3 (AKR1C3) belongs to a superfamily of NAD(P)H-dependent oxidoreductases, which metabolize prostaglandins and steroid hormones. It is involved in the pathogenesis of various skin diseases (see poster     # 311), such as atopic dermatitis (AD)1 and squamous cell carcinoma2. A major risk factor for the development and progression of these cutaneous diseases is a chronic exposure to polycyclic aromatic hydrocarbons and related environmental pollutants. These chemicals are able to bind and activate the aryl hydrocarbon receptor (AhR), a cytosolic transcription factor, that orchestrates respective adaptive and maladaptive responses. 
In its inactive state, the AhR is trapped in a multiprotein complex composed of the AhR, a c-Src kinase and heat-shock protein (hsp) 90. Upon activation, the complex dissociates and the AhR rapidly translocates to the nucleus to induce the expression of target genes, such as cytochrome P450 (CYP) 1A monooxygenases. A second mechanism involving the cell membrane is probably initiated by the soluble tyrosine kinase c-Src and the subsequent activation of the epidermal growth factor receptor (EGFR)3.
In this study we present a potential mechanism how different AhR ligands induce differential gene expression, incl. AKR1C3, in dependence of the non-canonical AhR signaling pathway.

The Aryl hydrocarbon receptor (AhR) induces the expression of aldo-keto reductase (AKR) 1C3 in keratinocytes in a ligand-specific manner.