De novo synthesis of cholesterol by ovine fetal and neonatal adrenocortical cells

Abstract

The present study compared the stocks of cholesterol present in adrenal cells from 120-day-old ovine fetuses and from newborn lambs, as well as the capacity of these cells to regulate their stock by de novo synthesis from C 2 units. Both free cholesterol and cholesteryl ester concentrations of mitochondrial fractions of adrenal glands from fetuses were lower than those from newborn lambs. In addition, the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) and the cholesterol side-chain cleavage activities were 2- and 5-fold lower, respectively, in fetal than in neonatal adrenals. After 2 days of culture in serum-free media, the cellular contents of cholesterol were similar in control and ACTH 1–24-treated cells for both fetuses and newborns. Moreover, ACTH 1–24 increased HMG-CoA reductase activity of both fetal and neonatal cells to the same extent. When cells were cultured in the presence of 2% horse serum, the cellular content of cholesterol on day 2 was enhanced only in the case of neonatal cells, but [ 14C]acetate incorporation in free cholesterol was decreased in both fetal and neonatal cells, while its incorporation in cholesteryl ester was increased. The presence of serum in the medium prevented the enhancing effect of ACTH 1–24 on the fetal HMG-CoA reductase activity but had no effect on that of neonatal cells. These data, together with preceding results, suggest that the low stores of cholesterol of ovine fetal adrenal cells result from a limited capacity to synthesize cholesterol and to some alteration in the uptake and/or metabolism of plasma lipoproteins, which in turn might reflect the low steroidogenic capacity of these cells.