Endocrine Abstracts (2013) 32 P971 | DOI: 10.1530/endoabs.32.P971

Role of retinol dehydrogenase 12 (RDH12) in the biosynthesis of 5[alpha]-androstane-3[beta],17[beta]-diol (3[beta]-diol) in the skin

Shu Fang Zheng & Van Luu-The

Laval University, Quebec, QC, Canada.

Using real-time PCR, we found that RDH12 is highly expressed in the skin of Macacafascicularis (mf). It has been known that RDH12 is a retinol dehydrogenase that catalyzes the reduction of retinal into retinol and play an important role in the visual cycle. Indeed, its deficiency is the cause of Leber’s congenital amaurosis 3, a genetic disorder characterized by retinal dystrophy affecting both rods and cones. Previously, we have shown that many of the members of the retinol dehydrogenase family, such as RDH1, 5, 11 and 16 could also metabolize 5α-reduced steroids, including DHT, the most potent natural.

In order to determine the possible role of RDH12 in a non-visual cycle and especially in the intracrine metabolisation of DHT in the skin, we perform real-time PCR to quantify its expression levels and in situ hybridization to localise its expression in the skin. To determine its activity, we construct expression vectors that express the coding region of human, mf and mouse RDH12 under the control of CMV promoter (pCMV-h,mf,mRDH12), and stably transfect the resulting vectors into HEK-293 cells.

Using cells stably expressed human, mouse and mf RDH12 in culture without addition of co-factor, we show that the enzyme catalyzes effectively the transformation of DHT into 3β-diol and 5α-androstane-3,17-dione (5α-dione) into 5α-androstane-3β-ol-17-one (epi-ADT). In situ hybridization shows that RDH12 is highly expressed in mf sebocytes. These data strongly suggest that RDH12 could play an important role in the skin, especially in sebocytes by controlling the intracrine concentration of DHT and retinoic acid levels. RDH12 could thus play an important in acneseborrhea, a disease due to altered sebocyte secretion andis influenced by DHT and retinoic acid. In addition, 3β-diol could also have a yet determined effect in the skin and sebocytes due to its ability to modulate ERβ.

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