Glucocorticoid metabolism in the newborn rat heart.
A relative cardiac hypertrophy has been observed in newborns chronically treated with dexamethasone. To test the hypothesis--that dexamethasone might alter steroid metabolism within the heart--rat pups were injected with vehicle, corticosterone (dosages 20 or 200 micrograms/pup/injection, or 1 mg/pup/injection) or dexamethasone (5 micrograms/pup/injection) on Day 2-6 and sacrificed on Day 7-8. Injections with dexamethasone in this dosage have induced the cardiac changes in this rat model. 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) activity was assessed in hearts from these adrenally intact rat pups by incubating tissues with 3H-corticosterone 10(-8) M for 60 min. On Day 7-8, controls transformed 10.3% +/- 1.1% (mean +/- SE) of the corticosterone (Compound B) to 11-dehydrocorticosterone (Compound A) generating 1.25 +/- 0.35 x 10(-12) moles A/mg protein (n = 8). Tissues from pups pretreated with corticosterone at all three dosages were not different from controls in percent metabolized and moles A/mg generated. In contrast, hearts from dexamethasone treated pups transformed only 4.5% +/- 1.0% of the corticosterone to A generating 3.19 +/- 0.05 x 10(-13) moles A/mg protein (n = 10) (P < 0.05 versus control in moles/mg protein metabolized). Cultured cardiomyocytes exposed to dexamethasone for 4 days in vitro also decreased their expression of 11 beta-OHSD mRNA. Readily metabolized endogenous glucocorticoids produced little or no effect on developing heart muscle while treatment with dexamethasone, a potent synthetic glucocorticoid, induced relative cardiac hypertrophy and downregulated 11 beta-OHSD mRNA expression and enzyme activity.
Brem
A S
AS
Division of Pediatric Nephrology, Rhode Island Hospital, Providence 02903, USA.
Bina
R B
RB
Klinger
J R
JR
King
T
T
Werner
J C
JC
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
D012333:RNA, Messenger; D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases