Department of Molecular and Cellular Sports Medicine, German Sport University Cologne, 50933 Cologne, Germany.
Endocrinology. 2011 Dec;152(12):4718-28. doi: 10.1210/en.2011-1164. Epub 2011 Oct 11.
Various products containing rarely characterized anabolic steroids are nowadays marketed as dietary supplements. Herein, the designer steroid methyl-1-testosterone (M1T) (17β-hydroxy-17α-methyl-5α-androst-1-en-3-one) was identified, and its biological activity, potential adverse effects, and metabolism were investigated. The affinity of M1T toward the androgen receptor (AR) was tested in vitro using a yeast AR transactivation assay. Its tissue-specific androgenic and anabolic potency and potential adverse effects were studied in a Hershberger assay (sc or oral), and tissue weights and selected molecular markers were investigated. Determination of M1T and its metabolites was performed by gas chromatography mass spectrometry. In the yeast AR transactivation assay, M1T was characterized as potent androgen. In rats, M1T dose-dependently stimulated prostate and levator ani muscle weight after sc administration. Oral administration had no effect but stimulated proliferation in the prostate and modulated IGF-I and AR expression in the gastrocnemius muscle in a dose-dependent manner. Analysis of tyrosine aminotransferase expression provided evidence for a strong activity of M1T in the liver (much higher after oral administration). In rat urine, 17α-methyl-5α-androstane-3α,17β-diol, M1T, and a hydroxylated metabolite were identified. In humans, M1T was confirmed in urine in addition to its main metabolites 17α-methyl-5α-androst-1-ene-3α,17β-diol and 17α-methyl-5α-androstane-3α,17β-diol. Additionally, the corresponding 17-epimers as well as 17β-hydroxymethyl-17α-methyl-18-nor-5α-androsta-1,13-dien-3-one and its 17-epimer were detected, and their elimination kinetics was monitored. It was demonstrated that M1T is a potent androgenic and anabolic steroid after oral and sc administration. Obviously, this substance shows no selective AR modulator characteristics and might exhibit liver toxicity, especially after oral administration.
目前，各种含有特征不明确的合成代谢类固醇的产品都被作为膳食补充剂推向市场。本文鉴定了设计类固醇甲睾酮（M1T）（17β-羟基-17α-甲基-5α-雄甾-1-烯-3-酮），并对其生物活性、潜在的不良反应和代谢进行了研究。使用酵母雄激素受体（AR）转激活测定体外测试了 M1T 对 AR 的亲和力。在 Hershberger 测定（sc 或口服）中研究了 M1T 的组织特异性雄激素和合成代谢效力以及潜在的不良反应，并研究了组织重量和选定的分子标记物。通过气相色谱-质谱法测定 M1T 及其代谢物。在酵母 AR 转激活测定中，M1T 被鉴定为有效的雄激素。在大鼠中，M1T 以剂量依赖性方式刺激 sc 给药后的前列腺和肛提肌重量。口服给药没有效果，但以剂量依赖性方式刺激前列腺增殖，并调节腓肠肌中的 IGF-I 和 AR 表达。分析酪氨酸氨基转移酶的表达为 M1T 在肝脏中的强活性提供了证据（口服给药后更高）。在大鼠尿液中，鉴定出 17α-甲基-5α-雄烷-3α，17β-二醇、M1T 和一种羟化代谢物。在人类尿液中，除了主要代谢物 17α-甲基-5α-雄-1-烯-3α，17β-二醇和 17α-甲基-5α-雄烷-3α，17β-二醇外，还证实了 M1T 的存在。此外，还检测到相应的 17-差向异构体以及 17β-羟甲基-17α-甲基-18-去甲-5α-雄甾-1,13-二烯-3-酮及其 17-差向异构体，并监测了它们的消除动力学。结果表明，M1T 经 sc 和口服给药后是一种有效的雄激素和合成代谢类固醇。显然，这种物质没有表现出选择性 AR 调节剂的特征，并且可能具有肝毒性，特别是口服给药后。
