Fowler, P.A.

O'Shaughnessy, P.

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      O'Shaughnessy, P., and Fowler, P.A. (2015) Aspects of UGT2B15 in the human. Toxicological Sciences, 143(2), pp. 230   Copyright © 2015 The Authors.     This work is made available under the Creative Commons Attribution 4.0 International License (CC BY 4.0).  Version: Published   http://eprints.gla.ac.uk/104907/       Deposited on:  13 April 2015.        Enlighten – Research publications by members of the University of Glasgow http://eprints.gla.ac.uk Letter to the EditorAspects of UGT2B15 in the HumanTo the Editor,In their interesting and important new article on humanUGT2B15, Divakaran et al. (2014) are to be congratulated for theirdetermination to go beyond transcripts and to measure proteinlevels in a meticulous way.These authors report an interesting post-natal sex differencein UGT2B15, with males expressing higher levels in the liverthan females, as previously demonstrated by Court (2010). Inour study (O’Shaughnessy et al., 2013), which was not men-tioned in the Divakaran et al. (2014) publication, we observed nosignificant difference in hepatic UGT2B15 transcript betweenmale and female fetuses at 11–21 weeks of gestation. This is de-spite the expression of androgen receptor (AR) transcript andprotein in the human fetal liver and the plentiful circulating tes-tosterone in the male human fetus at this time (O’Shaughnessyet al., 2007; 2013). It is very interesting that, despite the well-known sex-differentiating drive during the second trimester,this important hepatic enzyme does not show a sex differenceuntil post-natal life. This later developmental onset of a sex dif-ference in UGT2B15 may have important therapeutic implica-tions. Furthermore, the fact that we (O’Shaughnessy et al.,2013) observed no effect of maternal smoking on fetalhepatic UGT2B15 expression (unlike UGT2B17 expression) doesnot mean that in utero exposure to cigarette smoke chemicalsmight not also perturb programming of post-natal UGT2B15.Unfortunately, there does not appear to be any existing litera-ture on the effects of prenatal cigarette smoke exposure onthese enzymes in the human liver in childhood or adult life.Taken together, we now know from three well-poweredstudies that UGBTB15 expression is liver-predominant andclimbs steadily from 5 weeks of gestation onwards (Divakaranet al., 2014; Ekstrom et al., 2013; O’Shaughnessy et al., 2013), in-dicative of an important role in fetal and then adult hepaticfunction. Furthermore, because of its role in fetal programming,a better understanding of the development of the human livermore generally, and its response to adverse exposure throughmaternal recreational drugs (including cigarettes and alcohol),is critical. This knowledge will be important in supporting popu-lation-based studies relating the in utero environment to subse-quent adult health.AcknowledgmentFunding from the Medical Research Council, UK, MR/L010011/1.ReferencesCourt, M.H. (2010). Interindividual variability in hepaticdrug glucuronidation: studies into the role of age, sex,enzyme inducers, and genetic polymorphism using the hu-man liver bank as a model system. Drug Metab. Rev. 42,209–224.Divakaran, K., Hines, R.N., McCarver, D.G. (2014). Humanhepatic UGT2B15 developmental expression. Toxicol. Sci. 141,292–299.Ekstro¨m, L., Johansson, M., Rane, A. (2013). Tissue distributionand relative gene expression of UDP-glucuronosyltransfer-ases (2B7, 2B15, 2B17) in the human fetus. Drug Metab. Dispos.41, 291–295.O’Shaughnessy, P.J., Baker, P.J., Monteiro, A., Cassie, S.,Bhattacharya, S., Fowler, P.A. (2007). Developmental changesin human fetal testicular cell numbers and messenger ribo-nucleic acid levels during the second trimester. J. Clin.Endocrinol. Metab. 92, 4792–4801.O’Shaughnessy, P.J., Monteiro, A., Bhattacharya, S., Fraser, M.J.,Fowler, P.A. (2013). Steroidogenic enzyme expression in thehuman fetal liver and potential role in the endocrinology ofpregnancy. Mol. Hum. Reprod. 19, 177–187.Peter J. O’ShaughnessyCollege of Medical, Veterinary and Life Sciences,Institute of Biodiversity, Animal Health and ComparativeMedicine,University of Glasgow,Glasgow G61 1QH, United KingdomPaul A. FowlerDivision of Applied Medicine,Institute of Medical Sciences,University of Aberdeen,Aberdeen AB25 2ZD, United Kingdomdoi: 10.1093/toxsci/kfu252VC The Author 2015. Published by Oxford University Press onbehalf of the Society of Toxicology.This is an Open Access article distributed under the termsof the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permitsunrestricted reuse, distribution, and reproduction in anymedium, provided the original work is properly cited.230 | TOXICOLOGICAL SCIENCES, 2015, Vol. 143, No. 2 at Periodicals Dept on April 13, 2015http://toxsci.oxfordjournals.org/Downloaded from 

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Aspects of UGT2B15 in the human

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