We have four new units
Pathology Training Programme in Disease Modelling (60 cr)
Model of the MonthIn a recent study, Jokela et al. (Endocrinology 151:1884-1892, 2010) suggested that in mice, hydroxysteroid (17beta) dehydrogenase 7 (HSD17B7) is involved in the de novo synthesis of cholesterol and is essential for normal development during embryogenesis. Hydroxysteroid (17beta) dehydrogenase 7 (HSD17B7) has been shown to catalyze the conversion of both estrone to estradiol (17-ketosteroid reductase activity) and zymosterone to zymosterol (3-ketosteroid reductase activity involved in cholesterol biosynthesis) in vitro. To define the metabolic role of the enzyme in vivo, knockout mice deficient in the enzyme activity (HSD17B7KO) were generated. The data showed that the lack of HSD17B7 results in a blockage in the de novo cholesterol biosynthesis in mouse embryos in vivo, and HSD17BKO embryos die at embryonic day (E) 10.5. Analysis of neural structures revealed a defect in the development of hemispheres of the front brain with an increased apoptosis in the neuronal tissues. Morphological defects in the cardiovascular system were also observed from E9.5 onward. Mesodermal, endodermal, and hematopoietic cells were all detected by the histological analysis of the visceral yolk sac, whereas no organized vessels were observed in the knockout yolk sac. Immunohistological staining for platelet endothelial cell adhesion molecule-1 indicated that the complexity of the vasculature also was reduced in the HSD17B7KO embryos, particularly in the head capillary plexus and branchial arches. At E8.5-9.5, the heart development and the looping of the heart appeared to be normal in the HSD17B7KO embryos. However, at E10.5 the heart was dilated, and the thickness of the cardiac muscle and pericardium in the HSD17B7KO embryos was markedly reduced, and immunohistochemical staining for GATA-4 revealed that HSD17B7KO embryos had a reduced number of myocardial cells. The septum of the atrium was also defected in the knockout mice.
Image of the Month
A representative coronal PET image of a male Sprague-Dawley rat. Image is a summation from 5 to 30 min after injection of [11C]PK11195. Accumulation of the tracer is clearly visible in the thyroid glands, liver, brain, heart, lung, adrenal gland and kidneys (arrows) (Roivainen A et al.).
Jokela H, Rantakari P, Lamminen T, Strauss L, Ola R, Mutka A-L, Gylling H, Miettinen T, Pakarinen P, Sainio K, Poutanen M. Hydroxysteroid (17β) dehydrogenase 7 activity is essential for fetal de novo cholesterol synthesis and for neuroectodermal survival and cardiovascular differentiation in early mouse embryos. Endocrinology 151:1884-1892 (2010)
*Rantakari P, *Lagerbohm H, Kaimainen M, Suomela J-P, Strauss L, Sainio K, Pakarinen P, Poutanen M. Hydroxysteroid (17β) dehydrogenase 12 is essential for mouse organogenesis and embryonic survival. Endocrinology 151:1893-1901 (2010)
Shen Z, Saloniemi T, Rönnblad A, Järvensivu P, Pakarinen P, Poutanen M. Sex steroid-dependent and -independent action of hydroxysteroid (17beta) Dehydrogenase 2: evidence from transgenic female mice.
Endocrinology 150:4941-9 (2009)
Saloniemi T, Welsh M, Lamminen T, Saunders P, Mäkelä S, Streng T, Poutanen M. Human HSD17B1 expression masculinizes transgenic female mice. Mol Cell Endocrinol. 301:163-168 (2009)
Lankinen P, Mäkinen TJ, Pöyhönen TA, Virsu P, Salomäki S, Hakanen AJ, Jalkanen S, Aro HT, Roivainen A. (68Ga)-DOTAVAP-P1 PET imaging capable of demonstrating the phase of inflammation in healing bones and the progress of infection in osteomyelitic bones. Eur J Nucl Med Mol Imaging 35:352-64 (2008)
Shen Z., Peng Z, Sun Y., Väänänen H.K. Poutanen M., Overexpression of Human Hydroxysteroid (17-beta) Dehydrogenase 2 Induces Disturbance in Skeletal Metabolism in Young Male Mice. J. Bone and Mineral Res. 23:1217-1226 (2008).
Rantakari P., Strauss L., Kiviranta R., Lagerbohm H, Paviala J, Holopainen I., Vainio S., Pakarinen P., Poutanen M., Placenta defects and embryonic lethality resulting from disruption of mouse hydroxysteroid (17-beta) dehydrogenase 2 Gene. Mol. Endocrinol., 22:665-75 (2008).Seth A., Steel J.H., Nichol D., Pocock V., Kumaran M.K., Friath A., Mobberley M., Ryder T.A., Rowlerson A., Scott J., Poutanen M., White R., Parker M. The Transcriptional Corepressor RIP140 Regulates Oxidative Metabolism in Skeletal Muscle. Cell Metabolism, 6:236-45 (2007).