The androgenic anabolic steroid tetrahydrogestrinone produces dioxin-like effects via the aryl hydrocarbon receptor.
For a long time, athletes have used androgenic anabolic steroids (AASs) in an inappropriate and veiled manner with the aim of improving exercise performance or for cosmetic purposes. Abuse of AASs triggers adverse effects such as hepatocarcinogenesis, heart attacks, and aggressive behavior. However, AAS-induced toxicity is not completely understood at the molecular level. In the present study, we showed, by performing a dioxin response element (DRE)-luciferase reporter gene assay, that tetrahydrogestrinone (THG), a popular and potent androgen receptor agonist, has dioxin-like effects. In addition, we showed that THG increased cytochrome P-450 1A1 (CYP1A1) mRNA and protein levels, and enzyme activity. The gene encoding CYP1A1 is involved in phase 1 xenobiotic metabolism and a target gene of the aryl hydrocarbon receptor (AhR). Using the AhR antagonist CH-223191, we also examined whether the effects of THG on DRE activation depended on AhR. Our results suggest that synthetic anabolic steroids may have dioxin-like side effects that can disturb endocrine systems and may cause other side effects including cancer through AhR.
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
Hyo Youl
HY
Moon
Sun-Hee
SH
Kim
Sung Ho
SH
Ryu
Pann-Ghill
PG
Suh
D001391:Azo Compounds / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics; D004147:Dioxins / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D017930:Genes, Reporter / Q000187:drug effects / Q000235:genetics; D005867:Gestrinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D020218:Response Elements / Q000187:drug effects* / Q000235:genetics
C511621:2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide; D001391:Azo Compounds; D004147:Dioxins; D011720:Pyrazoles; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D005867:Gestrinone; C479553:tetrahydrogestrinone; D008156:Luciferases; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1