Human jejunal estrogen sulfotransferase and dehydroepiandrosterone sulfotransferase: immunochemical characterization of individual variation.
Sulfate conjugation is an important metabolic pathway for many drugs, xenobiotic compounds, and steroid hormones. Human tissues express five cytoplasmic sulfotransferase (ST) enzymes: estrogen ST (EST), dehydroepiandrosterone (DHEA) ST, and three phenol STs (PSTs). Both EST and DHEA ST can catalyze the sulfonation of steroid compounds, including exogenously administered steroids such as ethinyl estradiol. We set out to characterize immunochemically the nature and extent of individual variation in the expression of EST and DHEA ST in the human small intestine after Northern blot analysis had demonstrated that both enzymes were expressed in that tissue. Polyclonal antibodies to human EST and DHEA ST were developed, and Western blot analysis demonstrated that the antibodies were specific. We then performed quantitative Western blots of EST and DHEA ST in 62 samples of human jejunal mucosa. Large individual variations in immunoreactive EST and DHEA ST protein levels were present in those 62 tissue samples. However, there was not a significant correlation between levels of immunoreactive protein for the two enzymes (rs = 0.143, p = 0.262), indicating that EST and DHEA ST in the human jejunum are regulated independently. Furthermore, immunoreactive EST and DHEA ST protein levels in these samples did not differ significantly between the genders, and neither was correlated significantly with time of tissue storage, patient age, or underlying pathology. Frequency distribution histograms of immunoreactive protein values were skewed for both enzymes, and the DHEA ST frequency distribution seemed to be bimodal. These results represent a step toward understanding the molecular basis for individual variation in the expression and function of EST and DHEA ST in the human small intestine.
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Department of Pharmacology, Mayo Medical School/Mayo Clinic/Mayo Foundation, Rochester, MN 55905, USA.
Szumlanski
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Aksoy
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Weinshilboum
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000595:Amino Acid Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D018076:DNA, Complementary / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007120:Immunochemistry; D007223:Infant; D007579:Jejunal Diseases / Q000201:enzymology; D007583:Jejunum / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000737:chemistry; D015238:Sulfotransferases / Q000737:chemistry*
D018076:DNA, Complementary; D011994:Recombinant Proteins; D015238:Sulfotransferases; C019998:dehydroepiandrosterone sulfotransferase; C020122:estrone sulfotransferase