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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on December 9, 2005; DOI: 10.1124/jpet.105.093633


0022-3565/06/3163-1310-1317$20.00
JPET 316:1310-1317, 2006
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ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Developmental Expression of Aryl, Estrogen, and Hydroxysteroid Sulfotransferases in Pre- and Postnatal Human Liver

Zhengbo Duanmu, Amy Weckle, Sevasti B. Koukouritaki, Ronald N. Hines, Josie L. Falany, Charles N. Falany, Thomas A. Kocarek, and Melissa Runge-Morris

Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan (Z.D., A.W., T.A.K., M.R.-M.); Department of Pediatrics, Birth Defects Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin (S.B.K., R.N.H.); and Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama (J.L.F., C.N.F.)

Aryl- (SULT1A1), estrogen- (SULT1E1), and hydroxysteroid- (SULT2A1) sulfotransferases (SULTs) are active determinants of xenobiotic detoxication and hormone metabolism in the adult human liver. To investigate the role of these conjugating enzymes in the developing human liver, the ontogeny of immunoreactive SULT1A1, SULT1E1, and SULT2A1 expression was characterized in a series of 235 pre- and postnatal human liver cytosols ranging in age from early gestation to a postnatal age of 18 years. Interindividual variability in expression levels was apparent for all three SULTs in pre- and postnatal liver samples. Expression of the three SULTs displayed distinctly different developmental profiles. Semiquantitative Western blot analyses indicated that SULT1A1 and SULT2A1 immunoreactive protein levels were readily detectable in the majority of developmental human liver cytosols throughout the prenatal period. Whereas SULT1A1 expression did not differ significantly among the various developmental stages, SULT2A1 expression increased during the third trimester of gestation and continued to increase during postnatal life. By contrast, SULT1E1, a cardinal estrogen-inactivating enzyme, achieved the highest levels of expression during the earliest periods of gestation in prenatal male livers, indicating a requisite role for estrogen inactivation in the developing male. The present analysis suggests that divergent regulatory mechanisms are responsible for the differential patterns of hepatic SULT1A1, SULT1E1, and SULT2A1 immunoreactive protein levels that occur during pre- and postnatal human development, and implicates a major role for sulfotransferase expression in the developing fetus.


Received August 1, 2005; accepted December 7, 2005.

Address correspondence to: Dr. Melissa Runge-Morris, Institute of Environmental Health Sciences, Wayne State University, 2727 Second Avenue, Room 4000, Detroit, MI 48201. E-mail: m.runge-morris{at}wayne.edu




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