Tissue distribution of alpha 1-proteinase inhibitor messenger ribonucleic acid and its regulation by glucocorticoids in fetal and neonatal sheep.

alpha 1-Proteinase inhibitor (alpha 1-PI) controls several proteinases that play important roles during inflammation and tissue remodeling, but its function during mammalian development remains obscure. We have therefore studied the ontogeny of alpha 1-PI mRNA in selected fetal and newborn sheep tissues by Northern blotting. Furthermore, because glucocorticoids play important roles in fetal maturation and parturition in sheep, we measured the relative amounts of glucocorticoid receptor (GR) mRNA in the same tissues and compared the effect of dexamethasone (DEX) administration on alpha 1-PI mRNA levels in liver and kidney of fetal and adult sheep. In the ontogeny study, a 1.8-kb alpha 1-PI mRNA was found in fetal adrenal gland and lung at Days 60-70 but was low or undetectable in these tissues at later gestational ages. By contrast, the abundance of hepatic alpha 1-PI mRNA did not vary between Days 60 and 130 of gestation, but decreased significantly (p < 0.05) at term (Days 145-147) and in newborn lambs. In the fetal kidney, it was also present between Days 60 and 130, and its relative abundance increased significantly (p < 0.05) in term and newborn lambs. These changes did not correlate with GR mRNA abundance, which was relatively stable in all tissues except the kidney, where a significant (p < 0.05) decrease was observed in neonates.(ABSTRACT TRUNCATED AT 250 WORDS)