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 o f hydrocortisone on the synthesis and secretion of lipids and lipoprot eins. Human jejunal explants were cultured for 5 days at 37 degrees C in serum-free medium containing either [C-14]-oleic acid or [C-14]-ace tate, alone or supplemented with hydrocortisone (25 or 50 ng/ml). The uptake of [C-14]-oleic acid was associated with the production of trig lycerides, phospholipids, and cholesteryl esters, which were all affec ted by hydrocortisone. This hormonal agent (50 mu g) led to the marked reduction of secreted triglycerides (43%, P < 0.01), phospholipids (3 9%, P < 0.01), and cholesteryl esters (36%, P < 0.05) without altering the characteristic distribution of tissue and medium lipid classes. S imilarly, hydrocortisone significantly (P < 0.01) decreased (similar t o 60%) the incorporation of [C-14]-acetate into secreted free and este rified cholesterol in the medium. With [C-14]-oleic acid as a precurso r, hydrocortisone significantly diminished the delivery of chylomicron s and very low density lipoproteins to the medium while consistently e nhancing the secretion of high density lipoproteins. In parallel, [S-3 5]-methionine pulse-labeling of jejunal explants revealed the concomit ant inhibitory effect of hydrocortisone on apo B-100 synthesis and hyd rocortisone's stimulatory effect on apo B-48 and apo A-I. These studie s suggest that glucocorticoids play a critical role in lipoprotein pro cessing during intestinal development. (C) 1997 Wiley-Liss Inc.