Selective effects of hydrocortisone on intestinal lipoprotein and apolipoprotein synthesis in the human fetus

Studies employing human fetal intestine have yielded much interesting information on the role of polarized enterocytes in fat absorption and transport. Using the organ culture model, we examined the influence of hydrocortisone on the synthesis and secretion of lipids and lipoproteins. Human jejunal explants were cultured for 5 days at 37 degrees C in serum-free medium containing either [14C]-oleic acid or [14C]-acetate, alone or supplemented with hydrocortisone (25 or 50 ng/ml). The uptake of [14C]-oleic acid was associated with the production of triglycerides, phospholipids, and cholesteryl esters, which were all affected by hydrocortisone. This hormonal agent (50 micrograms) led to the marked reduction of secreted triglycerides (43%, P < 0.01), phospholipids (39%, P < 0.01), and cholesteryl esters (36%, P < 0.05) without altering the characteristic distribution of tissue and medium lipid classes. Similarly, hydrocortisone significantly (P < 0.01) decreased (approximately 60%) the incorporation of [14C]-acetate into secreted free and esterified cholesterol in the medium. With [14C]-oleic acid as a precursor, hydrocortisone significantly diminished the delivery of chylomicrons and very low density lipoproteins to the medium while consistently enhancing the secretion of high density lipoproteins. In parallel, [35S]-methionine pulse-labeling of jejunal explants revealed the concomitant inhibitory effect of hydrocortisone on apo B-100 synthesis and hydrocortisone's stimulatory effect on apo B-48 and apo A-1. These studies suggest that glucocorticoids play a critical role in lipoprotein processing during intestinal development.