Developmental changes in rat renal 11 beta-hydroxysteroid dehydrogenase.
11 beta-hydroxysteroid dehydrogenase (11 beta-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 11 beta-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 Sprague-Dawley rats. 11 beta-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 11 beta-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 microM NADP+, the apparent Km for corticosterone in the adult was 4.42 x 10(-6) M with a corresponding Vmax 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 Vmax of 2.08 x 10(-11) mol/min/mg protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Brem
A S
AS
Division of Pediatric Nephrology, Rhode Island Hospital, Providence.
Bina
B
B
Matheson
K L
KL
Barnes
J L
JL
Morris
D J
DJ
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D000831:Animals, Newborn; D003345:Corticosterone / Q000031:analogs & derivatives / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology* / Q000254:growth & development*; D007672:Kidney Cortex / Q000201:enzymology; D007700:Kinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; C003552:11-dehydrocorticosterone; D003345:Corticosterone