Implication of Human UGT2B7, 2B15, and 2B17 in 19-Norandrosterone Metabolism

• Published in: Frontiers in endocrinology (Lausanne) 2013, Vol.4, p.75-75
• Main Authors: Strahm, Emmanuel, Sjöberg, Ulf, Garle, Mats, Rane, Anders, Ekström, Lena
• Format: Article
• Language: English
• Subjects: 19-norandrosterone; anabolic androgenic steroid; Endocrinology; Endokrinologi och diabetes; Klinisk medicin; Medicin och hälsovetenskap; Nandrolone; UGT2B15; UGT2B7
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2013.00075

Nandrolone (19-nortestosterone) is an anabolic androgenic steroid commonly abused for doping purposes. Nandrolone is mainly metabolized in the liver into 19-norandrosterone prior to glucuronidation and excretion through urine over an extended period of time. Several UGTs (i.e., UGT2B7, UGT2B15, and UGT2B17) are thought to be the major enzymes responsible for conjugation of androgens in human. An in vitro study using recombinant enzymes expressed in insect cells showed that UGT1A4 and UGT2B7 are the two main enzymes responsible of 19-norandrosterone glucuronidation. However, the identity of the enzyme involved in nandrolone metabolism in vivo together with their relative contribution and regulation remain unknown. Inhibition assays using human liver microsomes (HLM) incubated with 19-norandrosterone and selective inhibitors confirmed that UGT2B7 and UGT2B15 are involved in 19-norandrosterone glucuronidation, since the presence of the specific UGT2B7 and UGT2B15 inhibitors gemfibrozil and valproic acid inhibited the 19-norandrosterone glucuronidation by 35 and 45%, respectively. HLM were genotyped for UGT2B15 D85Y, UGT2B7 H268Y, and the UGT2B17 deletion polymorphism. The glucuronidation activity on 19-norandrosterone was significantly higher in UGT2B15 DD than in the other UGT2B15 genotypes (p