Glucocorticoid effects on the embryonic chick heart. II. Alteration of oxidative metabolism.

The injection of cortisol phosphate (0.5 mg per egg) onto the chorioallantoic membrane of embryonic chicks at 12 days incubation depresses the rate of oxygen consumption in heart mitochondria isolated from the chicks 24 or 48 hours after the injection as compared to a saline injected control. The oxygen consumption is depressed using either reduced nicotinamide-adenine dinucleotide (NADH)-linked or flavin adenine dinucleotide (FADH)-linked substrates. The progressive inhibition of oxidation and adenosine triphosphate (ATP) production rate is related to the time after cortisol is injected. The treated mitochondria appear to function differently when NADH-linked and FADH-linked respiratory substrates are compared. Using NADH-linked substrates (site 1), adenosine diphosphate (ADP) was phosphorylated by mitochondria, even though the rate of phosphorylation was decreased; however, when FADH-linked substrates were used, incomplete phosphorylation was observed. The rate and the extent of calcium accumulation by embryonic chick heart mitochondria were also depressed by cortisol. These data suggest a defect in phosphorylation at site 2 following cortisol treatment but not at the site 1 linked energy transducing step. Whether these impairments of mitochondrial function result from catabolic turnover of the mitochondrial membrane components, excessive calcium accumulation by the mitochondria, or from the digestion of mitochondrial constituents, has not been delineated.

Glucocorticoid effects on the embryonic chick heart. I. Glucocorticoid enlargement of the heart.

Cortisol increases the heart weight relative to body weight following injection of growth suppressing amounts of the hormone on incubation days 9, 10, 13, and 15. Hormone administration increases glycogen, glycosaminoglycan (GAG), and total lipid concentration in the embryonic myocardium. Deoxyribonucleic acid (DNA) and protein concentration are decreased proportionally. Glycogen synthetase and radiosulphate incorporation into GAG are increased by the glucocorticoid. Lack of growth inhibition of the embryonic myocardium by glucocorticoids is not due to absence of glucocorticoid receptors. [3H]-Dexamethasone was shown to bind to a cytoplasmic and nuclear fraction of the chick heart. Binding to a cytoplasmic protein could be demonstrated in the heart at nine days of embryonic development and increased with developmental age. The increase in cardiac mass appears to be specific for the glucocorticoid hormones when compared with epinephrine and deoxycorticosterone. The latter two hormones did not increase cardiac mass.