The effects of hydrocortisone on the biosynthesis of sulfated glycoconjugates by human fetal lung.

Abstract

In order to study the regulation of sulfated glycoconjugate biosynthesis during human fetal lung development, an in vitro organ culture system was utilized. Tissue explants of human fetal lung maintained in organ culture undergo hydrocortisone-potentiated morphological differentiation. Human fetal lung tissue synthesized several classes of sulfated glycoconjugates, including sulfated glycosaminoglycans, sulfated lipids, and a class of glycoproteins containing sulfated oligosaccharide chains. These sulfated oligosaccharides were not released from the polypeptides under alkaline conditions that cleave O-glycosidically linked chains and were not degraded by a variety of chemical and enzymatic treatments which degraded sulfated glycosaminoglycans. Explants maintained in culture during a 6-day period incorporated increasing levels of 35SO4 into glycoconjugates with increases of 7-fold into heparin and heparan sulfate, 3-fold into sulfated glycoproteins, and 2-fold into sulfated lipids. In comparison, incorporation of [3H]mannose into glycoconjugates increased 4-fold, and the incorporation of [3H]thymidine into DNA increased 2- to 3-fold during this culture period. Tissues maintained in culture in the presence of hydrocortisone (10(-7) M) showed an enhanced incorporation of 35SO4 into heparin and heparan sulfate and into sulfated glycoproteins during the culture period compared to cultures maintained in the absence of hydrocortisone. However, the levels of 35SO4 incorporated into lipids, [3H]mannose incorporated into glycoproteins, and [3H]thymidine incorporated into DNA were markedly decreased in cultures maintained in the presence of 10(-7) M hydrocortisone. Only small differences in the synthesis of chondroitin sulfates and dermatan sulfate were observed during the 6-day period that lung tissues were maintained in culture in the presence or absence of hydrocortisone. Thus, the biosynthesis of specific sulfated glycoconjugates by human fetal lung tissues is probably regulated by both developmental events and by circulating steroids.