Molecular basis of perinatal changes in UDP-glucuronosyltransferase activity in maternal rat liver

The molecular basis of perinatal changes occurring in major UDP-glucuronosy ltransferase (UGT) family 1 isoforms and in UGT2B1, a relevant isoform belo nging to family 2, was analyzed in rat liver. Nonpregnant, pregnant (19-20 days of pregnancy), and two groups of postpartum animals corresponding to e arly and middle stages of lactation (2-4 and 10-12 days after delivery, res pectively) were studied. UGT activity determined in UDP-N-acetylglucosamine -activated microsomes revealed that bilirubin, p-nitrophenol, and ethynyles tradiol (17 beta -OH and 3-OH) but not androsterone and estrone glucuronida tion rates, were decreased in pregnant rats. Decreased enzyme activities re turned to control values after delivery. p-Nitrophenol, androsterone, and e strone conjugation rate increased in postpartum rats. Western blot analysis performed with anti-peptide-specific (anti-1A1, 1A5, 1A6, and 2B1) antibod ies revealed decreased levels of all family 1 isoforms and UGT2B1 during pr egnancy. In postpartum animals, protein level recovered (1A5 and 2B1) or ev en increased (1A1 and 1A6) with respect to control rats. Northern blot anal ysis suggested that expression of UGT proteins is down-regulated at a postt ranslational level during pregnancy and that increased levels of 1A1 and 1A 6 observed in postpartum rats were associated to increased mRNA. To establi sh whether prolactin is involved in up-regulation of UGT1A1 and 1A6 postpar tum, ovariectomized rats were treated with 300 mug of ovine prolactin per d ay for 7 days. The data indicated that prolactin was able to increase expre ssion of UGT1A6 (protein and mRNA) but not 1A1.Thus, prolactin is the likel y mediator of the increased expression of UGT1A6 observed in maternal liver postpartum.