Aberrant 11beta-hydroxysteroid dehydrogenase-1 activity in the cpk mouse: implications for regulation by the Ke 6 gene.
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.
Aziz
N
N
Department of Medicine, Children's Hospital, Boston, Massachusetts 02115, USA. aziz@a1.tch.harvard.edu
Brown
D
D
Lee
W S
WS
Naray-Fejes-Toth
A
A
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006649:Histocompatibility Antigens / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D008861:Microsomes / Q000201:enzymology; D009249:NADP / Q000502:physiology; D010088:Oxidoreductases; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
C079876:H2-Ke6 protein, mouse; D006649:Histocompatibility Antigens; D007527:Isoenzymes; D012333:RNA, Messenger; D009249:NADP; D010088:Oxidoreductases; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases