Ontogenic isoform switching of UDP-glucuronosyltransferase family 1 in rat liver

The liver undergoes dramatic changes in function during development. The development of UDP-glucuronosyltransferase family 1 (UGT1) isoforms was studied in livers from rats at 16-20days of gestation, at days 1, 2, 3, 4, and 7 of infancy, at days 14 and 28 of childhood, and at day 56 of young adulthood. We found developmental stage-specific switching of regulation of the rat UGT1 gene complex. UGT1A6 was expressed as a predominant component of UGTI in fetus liver, while other UGT1 isoforms were repressed. In contrast, expression of UGT1A1 Surged immediately after birth. Expression of UGT1A5 was transiently elevated in childhood. We also found age-dependent alternative usage of dual UGT1A6 promoters in rat liver. Since UGT1 A1 is the only bilirubin-glucuronidating isoform, the ontogeny of UGT1A1 in liver microsomes demonstrates that inadequate UGT1A1 proteins in the early neonatal period are linked to the common etiology of idiopathic hyperbilirubinemia in the newborn infant. (C) 2008 Elsevier Inc. All rights reserved.