Human DHRS7, promising enzyme in metabolism of steroids and retinoids?

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 155; no. Pt A; pp. 112 - 119
• Main Authors: Štambergová, Hana, Zemanová, Lucie, Lundová, Tereza, Malčeková, Beata, Skarka, Adam, Šafr, Miroslav, Wsól, Vladimír
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2016
• Subjects: Androstenedione - metabolism; Carbonyl reduction; Circular Dichroism; Cortisone - metabolism; DHRS7; Gene Expression Regulation, Enzymologic; Humans; Kinetics; Metabolism; Oxidoreductases - chemistry; Oxidoreductases - genetics; Oxidoreductases - metabolism; Phylogeny; Retinaldehyde - metabolism; Retinoids; SDR; Steroids; Steroids - metabolism; SDR; AKR; Retinoids; 17β-HSD; Metabolism; ER; DHRS7; Carbonyl reduction; DHRS7B; DHRS7C; RDH; 11β-HSD1; Steroids
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2015.09.041

•Amino acid sequence of DHRS7 is highly conserved in diverse species.•DHRS7 participates in the reductive metabolism of steroids and retinoids.•DHRS7 catalyzes reduction of several toxic compounds harmful to human health.•DHRS7 expression patterns were determined at both the mRNA and the protein levels. The metabolism of steroids and retinoids has been studied in detail for a long time, as these compounds are involved in a broad spectrum of physiological processes. Many enzymes participating in the conversion of such compounds are members of the short-chain dehydrogenase/reductase (SDR) superfamily. Despite great effort, there still remain a number of poorly characterized SDR proteins. According to various bioinformatics predictions, many of these proteins may play a role in the metabolism of steroids and retinoids. Dehydrogenase/reductase (SDR family) member 7 (DHRS7) is one such protein. In a previous study, we determined DHRS7 to be an integral membrane protein of the endoplasmic reticulum facing the lumen which has shown at least in vitro NADPH-dependent reducing activity toward several eobiotics and xenobiotics bearing a carbonyl moiety. In the present paper pure DHRS7 was used for a more detailed study of both substrate screening and an analysis of kinetics parameters of the physiologically important substrates androstene-3,17-dione, cortisone and all-trans-retinal. Expression patterns of DHRS7 at the mRNA as well as protein level were determined in a panel of various human tissue samples, a procedure that has enabled the first estimation of the possible biological function of this enzyme. DHRS7 is expressed in tissues such as prostate, adrenal glands, liver or intestine, where its activity could be well exploited. Preliminary indications show that DHRS7 exhibits dual substrate specificity recognizing not only steroids but also retinoids as potential substrates and could be important in the metabolism of these signalling molecules.