Glucocorticoids accelerate the ontogenetic transition of cardiac ventricular myosin heavy-chain isoform expression in the rat: promotion by prenatal exposure to a low dose of dexamethasone.
Cardiac myosin heavy chain expression undergoes a perinatal transition from predominance of beta-MHC to alpha-MHC. In the current study, we tested the effects of glucocorticoids in this early transition period, by treating pregnant rats with dexamethasone on gestational days 17, 18 and 19, using doses below (0.05 mg/kg), at (0.2 mg/kg) or above (0.8 mg/kg) the threshold for growth retardation. Cardiac MHC isoforms were resolved with a denaturing SDS-PAGE system, followed by quantitative densitometry. In normal animals alpha-MHC was only 10% of the total on gestational day 18 but rose to 35% by postnatal day 1, and to 95% by the end of the first month postpartum. During the early phase of this transition, the lowest dose of dexamethasone significantly promoted alpha-MHC expression without inhibiting body or heart growth; regression analysis indicated a 40% increase in the slope of MHC isoform transition with respect to tissue weight. In contrast, the higher, growth-retarding doses of dexamethasone either failed to enhance alpha-MHC expression or caused biphasic changes, with inhibition at ages corresponding to the onset of weight deficits; regression analysis indicated that the effects of the higher doses on MHC could all be accounted for by changes in tissue weight. Glucocorticoid levels rise substantially in the period surrounding parturition, and serve to program the development and coupling of adenylate cyclase to membrane receptors; because adenylate cyclase has been shown to elicit the beta-MHC to alpha-MHC transition in vitro, our results suggest that glucocorticoids, along with thyroid hormone and beta-adrenergic stimulation, influence the ontogenetic program of MHC isoform transition.(ABSTRACT TRUNCATED AT 250 WORDS)
Bian
X
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Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Briggs
M M
MM
Schachat
F H
FH
Seidler
F J
FJ
Slotkin
T A
TA
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005333:Fetus / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D006352:Heart Ventricles / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000096:biosynthesis*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis
D003907:Dexamethasone; D009218:Myosins