Investigation of Testosterone, Androstenone, and Estradiol Metabolism in HepG2 Cells and Primary Culture Pig Hepatocytes and Their Effects on 17βHSD7 Gene Expression

Steroid metabolism is important in various species. The accumulation of androgen metabolite, androstenone, in pig adipose tissue is negatively associated with pork flavor, odour and makes the meat unfit for human consumption. The 17β-hydroxysteroid dehydrogenase type 7 (17βHSD7) expressed abundantly in porcine liver, and it was previously suggested to be associated with androstenone levels. Understanding the enzymes and metabolic pathways responsible for androstenone as well as other steroids metabolism is important for improving the meat quality. At the same time, metabolism of steroids is known to be species- and tissue-specific. Therefore it is important to investigate between-species variations in the hepatic steroid metabolism and to elucidate the role of 17βHSD7 in this process. Here we used an effective methodological approach, liquid chromatography coupled with mass spectrometry, to investigate species-specific metabolism of androstenone, testosterone and beta-estradiol in HepG2 cell line, and pig cultured hepatocytes. Species- and concentration-depended effect of steroids on 17βHSD7 gene expression was also investigated. It was demonstrated that the investigated steroids can regulate the 17βHSD7 gene expression in HepG2 and primary cultured porcine hepatocytes in a concentration-dependent and species-dependent pattern. Investigation of steroid metabolites demonstrated that androstenone formed a 3′-hydroxy compound 3β-hydroxy-5α-androst-16-ene. Testosterone was metabolized to 4-androstene-3,17-dione. Estrone was found as the metabolite for β-estradiol. Inhibition study with 17βHSD inhibitor apigenin showed that apigenin didn't affect androstenone metabolism. Apigenin at high concentration (50 μM) tends to inhibit testosterone metabolism but this inhibition effect was negligible. Beta-estradiol metabolism was notably inhibited with apigenin at high concentration. The study also established that the level of testosterone and β-estradiol metabolites was markedly increased after co-incubation with high concentration of apigenin. This study established that 17βHSD7 is not the key enzyme responsible for androstenone and testosterone metabolism in porcine liver cells. © 2012 Chen et al

17β-hydroxysteroid dehydrogenase type 7 - An ancient 3-ketosteroid reductase of cholesterogenesis

17 beta -hydroxysterold dehydrogenase type 7 (17 beta -HSD7) is a novel estrogenic hydroxysteroid dehydrogenase from mammals. We modeled the three-dimensional structure of human 17 beta -HSD7, analyzed the phylogeny of 17 beta -HSD7 homologues and determined its expression pattern by in silico Northern blotting. Predominant expression is found not only in reproductive tissues (breast, ovary, placenta) but also in liver and developing brain, principal sites of cholesterol synthesis. The substrate binding pocket is opening towards a conserved membrane-associated helix, which is indicative for a conversion of a membrane component. 17 beta -HSD7 shows significant homology to a yeast 3-ketosteroid reductase (ERG27) involved in ergosterol biosynthesis. Our results lead to the conclusion that 17 beta -HSD7 is not only involved in estradiol production but plays another land possibly more important) role as a 3-ketosteroid reductase in cholesterogenesis. This agrees with the striking absence of 17 beta -HSD7 homologues in the complete genomes of Drosophila and C. elegans which are both auxotrophic for cholesterol

Determination of cDNA, gene structure and chromosomal localization of the novel human 17beta-hydroxysteroid dehydrogenase type 7

We have identified human 17L-hydroxysteroid dehydrogenase type 7 (17L-HSD 7). The novel human cDNA encodes a 37 kDa protein that shows 78 and 74 % amino acid identity with rat and mouse 17L-HSD 7, respectively. These enzymes are responsible for estradiol production in the corpus luteum during pregnancy, but are also present in placenta and several steroid target tissues (breast, testis and prostate) as revealed by RT-PCR. The human 17L-HSD 7 gene (HSD17B7) consists of nine exons and eight introns, spanning 21.8 kb and maps to chromosome 10p11.2 close to susceptibility loci for tumor progression, obesity and diabetes. The HSD17B7 promoter (1.2 kb) reveals binding sites for brain-specific and lymphoid transcription factors corresponding to additional expression domains in hematopoietic tissues and the developing brain as identified by in silico Northern blot

Deutsche Verwaltungsblätter : Blätter für administrative Praxis

Editors: 1851-60, Karl Brater; 1861-94, August Luthardt; 1895-1922, Karl von Krazeisen (with Max von Seydel, 1895-1901); 1925-37, Ottmar KollmannMode of access: Internet.Title varies: 1851-1922, Blätter für administrative Praxis; 1925-33, Bayerische Verwaltungsblätter : Blätter für administrative PraxisAbsorbed by Deutsche Verwaltung in 1938Signature of Ernst Münch in vols. 1-4