INVESTIGADORES
SANCHEZ POZZI Enrique Juan
artículos
Título:
Molecular Basis of perinatal changes in UDP-glucuronosyltransferase activity in maternal rat liver.
Autor/es:
LUQUITA, MARCELO G; CATANIA, VIVIANA A; ENRIQUE JUAN SANCHEZ POZZI; VEGGI, LUIS M; HOFFMAN, TIM; PELLEGRINO, JOSÉ M; IKUSHIRO, S; YOSHIKAZU, E; IYANAGI, T; VORE, MARY; MOTTINO, ALDO D
Revista:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Editorial:
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
Referencias:
Año: 2001 vol. 298 p. 49 - 56
ISSN:
0022-3565
Resumen:
The molecular basis of perinatal changes occurring in major UDP-glucuronosyltransferase (UGT) family 1 isoforms and in UGT2B1, a relevant isoform belonging to family 2, was analyzed in rat liver.
Nonpregnant, pregnant (19-20 days of pregnancy), and two groups of
postpartum animals corresponding to early and middle stages of lactation
(2-4 and 10-12 days after delivery, respectively) were studied. UGT activity
determined in UDP-N-acetylglucosamine-activated microsomes revealed
that bilirubin, p-nitrophenol, and ethynylestradiol (17beta-OH and 3-OH)
but not androsterone and estrone glucuronidation rates, were decreased
in pregnant rats. Decreased enzyme activities returned to control values
after delivery. p-Nitrophenol, androsterone, and estrone conjugation
rate increased in postpartum rats. Western blot analysis performed with
anti-peptide-specific (anti-1A1, 1A5, 1A6, and 2B1) antibodies revealed
decreased levels of all family 1 isoforms and UGT2B1 during pregnancy.
In postpartum animals, protein level recovered (1A5 and 2B1) or even
increased (1A1 and 1A6) with respect to control rats. Northern blot
analysis suggested that expression of UGT proteins is down-regulated at a
post-translational level during pregnancy and that increased levels of
1A1 and 1A6 observed in postpartum rats were associated to increased
mRNA. To establish whether prolactin is involved in up-regulation of
UGT1A1 and 1A6 postpartum, ovariectomized rats were treated with 300
microg of ovine prolactin per day for 7 days. The data indicated that
prolactin was able to increase expression of UGT1A6 (protein and mRNA)
but not 1A1. Thus, prolactin is the likely mediator of the increased
expression of UGT1A6 observed in maternal liver postpartum.