Aberrant 11beta-hydroxysteroid dehydrogenase-1 activity in the cpk mouse: implications for regulation by the Ke 6 gene

Endocrinology
N AzizA Naray-Fejes-Toth

Abstract

Glucocorticoids have been used to create experimental polycystic kidney disease in rodents and to induce cysts in embryonic kidneys cultures. In addition, the plasma corticosterone levels are higher in a heritable murine model of polycystic kidney disease, cpk mice, in the first postnatal week. Previously, we had shown that the 11beta-hydroxysteroid dehydrogenase-1 (11betaHSD-1) gene is down-regulated in the cpk mice in a coordinated pattern with the Ke 6 gene. In this study, we measured the level of 11betaHSD-1 activity in kidney and liver tissues of cpk homozygote mice and found a reduction in its activity only in the kidney, not in the liver. The activity of the 11betaHSD-1 enzyme appears to be tightly correlated to the level of Ke 6 protein in these tissues. We discuss the possibility that the activity of the 11betaHSD-1 enzyme may be regulated by the Ke 6 enzyme. Ke 6 gene expression has been located to the outer stripe region of rodent kidneys, which is the same region of expression as that for the 11betaHSD-1 gene. These results suggest that down-regulation of the Ke 6 gene may lead to elevated corticosterone levels, mediated through an inhibition of 11betaHSD-1 activity.

Citations

Feb 21, 2002·The Journal of Clinical Investigation·Xiaoying HouLisa M Guay-Woodford
Feb 4, 2014·The Journal of Steroid Biochemistry and Molecular Biology·Jianguo LiuDandan Yang
Jun 23, 2007·The Journal of Steroid Biochemistry and Molecular Biology·Joaquín VillarIgnacio Encío
Jun 1, 2005·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Georges PelletierFernand Labrie
Jul 3, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhijun ChenJ Kalervo Hiltunen
Nov 6, 2003·American Journal of Physiology. Renal Physiology·Lisa M Guay-Woodford

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