Developmental Expression of the Cytosolic Sulfotransferases in Human Liver

• Published in: Drug metabolism and disposition 2019-06, Vol.47 (6), p.592-600
• Main Authors: Dubaisi, Sarah, Caruso, Joseph A, Gaedigk, Roger, Vyhlidal, Carrie A, Smith, Philip C, Hines, Ronald N, Kocarek, Thomas A, Runge-Morris, Melissa
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Cytosol - metabolism; Deactivation; Developmental stages; DNA-directed RNA polymerase; Female; Gene expression; Gene families; Gene sequencing; Gestation; Hormones; Humans; Inactivation; Infant; Infant, Newborn; Liver; Liver - metabolism; Male; Metabolism; Middle Aged; Neurotransmitters; Organic chemistry; Polymerase chain reaction; Proteins; Proteomics; Reverse transcription; Ribonucleic acid; RNA; RNA, Messenger - metabolism; Sterols; Sulfonation; Sulfotransferases - metabolism; Xenobiotics; Young Adult
• ISSN: 0090-9556; 1521-009X
• DOI: 10.1124/dmd.119.086363

The liver is the predominant organ of metabolism for many endogenous and foreign chemicals. Cytosolic sulfotransferases (SULTs) catalyze the sulfonation of drugs and other xenobiotics, as well as hormones, neurotransmitters, and sterols, with consequences that include enhanced drug elimination, hormone inactivation, and procarcinogen bioactivation. SULTs are classified into six gene families, but only SULT1 and SULT2 enzymes are expressed in human liver. We characterized the developmental expression patterns of SULT1 and SULT2 mRNAs and proteins in human liver samples using reverse transcription quantitative polymerase chain reaction (RT-qPCR), RNA sequencing, and targeted quantitative proteomics. Using a set of prenatal, infant, and adult liver specimens, RT-qPCR analysis demonstrated that ( ) expression did not vary appreciably during development; , , and mRNA levels were highest in prenatal and/or infant liver, and , , and mRNA levels were highest in infant and/or adult. Hepatic ( ), , and mRNA levels were low regardless of developmental stage. Results obtained with RNA sequencing of a different set of liver specimens (prenatal and pediatric) were generally comparable results to those of the RT-qPCR analysis, with the additional finding that expression was highest during gestation. Analysis of SULT protein content in a library of human liver cytosols demonstrated that protein levels generally corresponded to the mRNAs, with the major exception that SULT1C4 protein levels were much lower than expected based on mRNA levels. These findings further support the concept that hepatic SULTs play important metabolic roles throughout the human life course, including early development.