Perinatal myocardial DNA and protein changes in the lamb: Effect of cortisol in the fetus

Myocardial growth during fetal life is accomplished by proliferation of the number of myocytes (hyperplasia). Shortly after birth, normal growth of th e heart is predominantly due to increase in cell size (hypertrophy), and my ocytes largely lose the capability to replicate. This change is characteriz ed by a decrease in myocardial DNA concentration and an increase in protein / DNA concentration ratio. Among many of the events associated with birth i s an increase in plasma cortisol concentrations in the few days before deli very of the fetus. To determine the possible role of cortisol in the postna tal change in myocardial growth, we measured DNA and protein concentrations in the free walls of the left (LV) and right (RV) ventricles in normal fet al lambs, normal newborn lambs, and in fetal lambs in which cortisone was i nfused for 72-80 h into the left coronary artery, which we showed does not perfuse the RV free wall. Normally, fetal RV DNA is higher than LV DNA conc entration, and DNA/protein ratio is lower in RV than in LV. It is suggested that this could be related to the greater load on the RV. Postnatally, pro tein concentrations increase progressively, but DNA remains the same in bot h ventricles, and protein/DNA ratios increase. Cortisol, infused to achieve normal prenatal levels in LV myocardium, markedly decreases LV DNA without affecting RV DNA concentrations. The present study indicates that cortisol inhibits myocyte replication and that cortisol simulates the change in myo cardial growth pattern normally occurring after birth. It raises concerns r egarding prenatal administration of glucocorticoids to mothers to mature th e fetal lungs before preterm delivery.