title: Dietary green and white teas suppress UDP-glucuronosyltransferase UGT2B17 mediated testosterone glucuronidation.
abstract: The anabolic steroid testosterone can be used by athletes to enhance athletic performance and muscle growth. UDP-glucuronosyltransferase (UGT2B17) is the key enzyme involved in the glucuronidation of testosterone to testosterone glucuronide, which also serves as a marker for the testosterone/epitestosterone (T/E) ratio used to detect testosterone abuse in sport. Inhibitors of testosterone glucuronidation could have an impact on circulating testosterone levels, thus aiding performance, as well as potentially affecting the urinary T/E ratio and therefore masking testosterone abuse. Previous reports have revealed that non-steroidal, anti-inflammatory drugs, diclofenac and ibuprofen, inhibit the UGT2B17 enzyme. The aim of this study is to analyse dietary tea samples for inhibition of testosterone glucuronidation and, where inhibition is present, to identify the active compounds. Analysis of testosterone glucuronidation was conducted by performing UGT2B17 assays with detection of un-glucuronidated testosterone using high performance liquid chromatography. The results from this study showed that testosterone glucuronidation was inhibited by the green and white tea extracts, along with specific catechin compounds, notably: epicatechin, epigallocatechin gallate (EGCG) and catechin gallate. The IC50 inhibition value for EGCG was determined, using a Dixon plot, to be 64 μM, equalling the most active NSAID inhibitor diclofenac. Thus, common foodstuffs and their constituents, for the first time, have been identified as inhibitors of a key enzyme involved in testosterone glucuronidation. Whilst these common compounds are not substrates of the UGT2B17 enzyme, we showed that they inhibit testosterone glucuronidation which may have implications on current doping control in sport.
authors.affiliation: School of Life Sciences, Kingston University, London, UK. k0713450@kingston.ac.uk
authors.forename: Carl
authors.initials: C
authors.lastname: Jenkinson
authors.forename: Andrea
authors.initials: A
authors.lastname: Petroczi
authors.forename: James
authors.initials: J
authors.lastname: Barker
authors.forename: Declan P
authors.initials: DP
authors.lastname: Naughton
mesh_terms: D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020723:Glucuronic Acid / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D015778:Minor Histocompatibility Antigens; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D011208:Powders; D013662:Tea / Q000737:chemistry*; D013739:Testosterone / Q000378:metabolism*; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D015778:Minor Histocompatibility Antigens; D010936:Plant Extracts; D011208:Powders; D013662:Tea; D013739:Testosterone; D020723:Glucuronic Acid; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human