Sex differences in UDP-glucuronosyltransferase 2B17 expression and activity

Carla J Gallagher; Renee M Balliet; Dongxiao Sun; Gang Chen; Philip Lazarus

doi:10.1124/dmd.110.035345

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Sex differences in UDP-glucuronosyltransferase 2B17 expression and activity

Journal article

Open access

Peer reviewed

Sex differences in UDP-glucuronosyltransferase 2B17 expression and activity

Carla J Gallagher, Renee M Balliet, Dongxiao Sun, Gang Chen and Philip Lazarus

Drug metabolism and disposition, Vol.38(12), pp.2204-2209

12/2010

DOI: https://doi.org/10.1124/dmd.110.035345

Handle:

https://hdl.handle.net/2376/106628

PMCID: PMC2993461

PMID: 20810538

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Abstract

Gene Expression Regulation, Enzymologic

Glucuronosyltransferase - genetics

Glucuronides - metabolism

Glucuronosyltransferase - metabolism

Minor Histocompatibility Antigens

Humans

RNA, Messenger - analysis

Female

Male

Microsomes, Liver - enzymology

Sex Characteristics

UDP-glucuronosyltransferases (UGTs) are enzymes involved in the metabolism of steroid hormones, carcinogens, cancer chemotherapy agents, and addictive agents from cigarettes. Because the UGT2B family of genes has been linked to hormonal regulation in human cell lines in vitro, we hypothesized that there may be sex-related differences in the expression and activity of these genes in human tissues. To evaluate whether there are sex differences in UGT2B expression and activity, we examined 103 normal human liver specimens for UGT2B expression by real-time polymerase chain reaction and in vitro glucuronidation activities in human liver microsomes (HLM). Men exhibited an approximately 4-fold higher level of expression of UGT2B17 than women (p = 0.007). Consistent with the increased expression of UGT2B17 in men, HLM from men also had a higher level of glucuronidation activity than HLM from women against three UGT2B17 substrates: 3-fold higher for 17-dihydroexemestane (p = 0.002); 3-fold higher for 3-hydroxycotinine (p < 0.001); and 1.5-fold higher for suberoylanilide hydroxamic acid (p = 0.014). When we stratified by UGT2B17 gene deletion genotype, similar patterns were observed for all three substrates, with HLM from men with the UGT2B17 (+/+) or (+/0) genotypes exhibiting significantly higher levels of glucuronidation activity against all three substrates compared with HLM from women. These data suggest that men have a higher amount of UGT2B17 glucuronidation activity then women. This sex difference in UGT2B17 gene expression and corresponding protein activity could potentially result in different levels of carcinogen detoxification or drug elimination in men versus women.

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Title: Sex differences in UDP-glucuronosyltransferase 2B17 expression and activity
Creators: Carla J Gallagher - Department of Pharmacology, Penn State College of Medicine, 500 University Drive, CH69, Hershey, PA 17033, USA
Renee M Balliet
Dongxiao Sun
Gang Chen
Philip Lazarus
Publication Details: Drug metabolism and disposition, Vol.38(12), pp.2204-2209
Academic Unit: Pharmaceutical Sciences, Department of
Publisher: United States
Grant note: R00 CA131477 / NCI NIH HHS R01 DE013158 / NIDCR NIH HHS K99-CA131477 / NCI NIH HHS K99 CA131477 / NCI NIH HHS R01-DE13158 / NIDCR NIH HHS
Identifiers: 99900547243701842
Language: English
Resource Type: Journal article