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

Nazneen Aziz, Dennis Brown, Wen Sen Lee, Aniko Naray-Fejes-Toth

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 11β-hydroxysteroid dehydrogenase-1 (11βHSD-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 11βHSD-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 11βHSD-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 11βHSD-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 11βHSD-1 gene. These results suggest that down-regulation of the Ke 6 gene may lead to elevated corticosterone levels, mediated through an inhibition of 11βHSD-1 activity.

Original languageEnglish
Pages (from-to)5581-5588
Number of pages8
JournalEndocrinology
Volume137
Issue number12
DOIs
Publication statusPublished - Jan 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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