Developmental changes in rat renal 11β-hydroxysteroid dehydrogenase

Andrew S. Brem, Bobby Bina, Karen L. Matheson, Jeffrey L. Barnes, David J. Morris

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

11β-hydroxysteroid dehydrogenase (11β-OHSD) transforms endogenous glucocorticoids to their respective 'biologically inert' 11-dehydro derivatives. A decrease in enzyme activity allows glucocorticoids to induce mineralocorticoid-like renal sodium retention. Since positive sodium balance is required for optimum growth in the newborn, we hypothesized that renal 11β-OHSD activity would be low in the postnatal period, a time of active growth. To test this, incubations with corticosterone were carried out using minces or homogenates prepared from kidneys of newborn, 8-day-old, and mature Spague-Dawley rats. 11β-OHSD activity in renal minces, assessed by the percent of corticosterone (10-8 M) transformed to 11-dehydrocorticosterone (compound A), was significantly lower in the newborn kidney (newborn 45.7 ± 3.8%, 8 day 70.2 ± 3.8%, and adult 73.4 ± 3.1%, P < 0.001 1 vs. 8 day). Parallel studies were conducted using an antibody directed against liver 11β-OHSD counter stained with immunofluorescent labeled IgG. Kidneys from mature rats were brightly stained at S2 and S3 segments of proximal tubules. In contrast, staining was barely detectable in kidneys from the newborn and 8-day-old rats. When enzyme kinetics were examined in kidney homogenates (average protein concentration 2.5 mg/ml) in the presence of 200 μM NADP+, the apparent Km for corticosterone in the adult was 4.42 x 10-6 M with a corresponding V(max) of 1.33 x 10-9 mol/min/mg protein, while the apparent Km for corticosterone in the newborn was calculated to be 12.8 x 10-8 M with a V(max) of 2.08 x 10-11 mol/min/mg protein. Thus 11β-OHSD activity appears diminished in the newborn kidney secondary to a decrease in the renal content of the enzyme and the lower apparent Km and V(max) for corticosterone.

Original languageEnglish (US)
Pages (from-to)679-683
Number of pages5
JournalKidney international
Volume45
Issue number3
DOIs
StatePublished - Mar 1994

ASJC Scopus subject areas

  • Nephrology

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