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

Abstract

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.

24-Hydroxycholesterol Sulfation by Human Cytosolic Sulfotransferases: Formation of Monosulfates and Disulfates, Molecular Modeling, Sulfatase Sensitivity, and Inhibition of Liver X Receptor Activation

“…Similar to SULT2B1b, SULT1E1 displayed a strong preference for the formation of the 3-monosulfate, although with a better affinity but lower activity. SULT1E1 is not as widely expressed in tissues as SULT2B1b being detected primarily in estrogen-responsive tissues, although low levels are present in liver (Duanmu et al, 2006). SULT2A1 is the major SULT expressed in liver and has a relatively broad substrate reactivity being capable of conjugating 3␣-and 3␤-hydroxysteroids, estrogens, and aliphatic hydroxyls in xenobiotics .…”

Interactions of the human cytosolic sulfotransferases and steroid sulfatase in the metabolism of tibolone and raloxifene

“…SULT1E1 and SULT2A1 are also of interest since SULT1E1 can form raloxifene disulfate and SULT2A1 can generate the 3-OH Tib disulfates (10,12). SULT1E1 is expressed in hormonally responsive tissues including breast, endometrium and prostate as well as the liver and GI tract (8,14,(22)(23)(24). SULT2A1 is present in relatively large amounts in the liver and adrenals but is not detectable in the breast, endometrium and prostate (15,24,25).…”

Redox regulation of human estrogen sulfotransferase (hSULT1E1)

“…Sulfation is believed to be involved in the inactivation of estrogens in target tissues [7]. Sulfation of active 17β-estradiol (E 2 ) forms inactive estradiol sulfate, which can be reactivated following desulfation by estrogen sulfatase [8].…”