Measuring by Hand: Arsenic Picked Up from the Playground

Background: We have recently discovered that human type 12 17β-HSD (h17β-HSD12), a homolog of type 3 17β-HSD, is a new estrogen-specific 17β-hydroxysteroid dehydrogenase involved in the production of estradiol (E2). To further characterize this estradiol-producing enzyme, we have isolated the corresponding cDNA in the cynomolgus monkey (Macaca fascicularis), characterized its enzymatic activities and performed cellular localization using in situ hybridization. Results: Using HEK-293 cells stably expressing Macaca fascicularis type 12 17β-HSD (mf17βHSD12), we have found that the mf17β-HSD12 catalyzes efficiently and selectively the transformation of El into E2, in analogy with the h17β-HSD12. We have also quantified the mf17βHSD12 mRNA expression levels in a series of Macaca fascicularis tissues using Quantitative RealTime PCR. The Macaca fascicularis 17β-HSD12 mRNA is widely expressed with the highest levels tissues found in the cerebellum, spleen and adrenal with moderate level observed in all the other examined, namely the testis, ovary, cerebral cortex, liver, heart, prostate, mammary gland, myometrium, endometrium, skin, muscle and pancreas. To gain knowledge about the cellular localization of the mf17β-HSD12 mRNA expression, we performed in situ hybridization using a 35Slabeled cRNA probe. Strong labeling was observed in epithelial cells and stromal cells of the mammary gland. In the uterus, the labeling is detected in epithelial cells and stromal cells of the endometrium. Conclusion: These results strongly suggest that the Macaca fascicularis 17β-HSD12 is an essential partner of aromatase in the biosynthesis of estradiol (E2). It strongly suggests that in the estradiol biosynthesis pathway, the step of 17-ketoreduction comes after the step of the aromatization (the aromatization of 4-androstendione to estrone followed by the conversion of estrone into estradiol by estrogen specific l7β-HSDs) which is in contrast with the hypothesis suggesting that 4androstenedione is converted to testosterone followed by the aromatization of testosterone. Published: 5 February 2007 BMC Biochemistry 2007, 8:2 doi:10.1186/1471-2091-8-2 Received: 6 April 2006 Accepted: 5 February 2007 This article is available from: http://www.biomedcentral.com/1471-2091/8/2 © 2007 Liu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.