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Although most anabolic and androgenic effects are expressed by the androgen receptor, some anabolic steroids can function outside the androgen receptor, and in vitro we examined the effects of a broad spectrum of compounds in the human endocrine system. Among these compounds were the synthetic analog of the androgen receptor (androstenedione), which selectively binds to the androgen receptor and was well-inducible in the cell line MCF-7, and the synthetic derivative of the steroid type 1 receptor antagonist (androstenedione, androstenol-O-methyl), which binds to the more specific type 1 receptor. In addition, androstenedione was found to bind androgen to androgen receptor and to type 1 receptor. The androgen receptor, the type 1 receptor antagonist, and androstenedione also blocked the anabolic actions mediated by GH, GH and testosterone. Androstenedione also blocked GH synthesis and the anabolic activity mediated by GH and testosterone. These results demonstrate that androstenedione is a ligand for the androgen receptor, a key androgen receptor co-receptor, and a co-activator of the type 1 receptor. In addition, we demonstrated that type-1 receptor antagonists were potent anabolic/anorexigenic inhibitors of androgen-mediated anabolism in a GH-deficient model; a role for these compounds in other anabolic/androgenic drugs has not been established. Moreover, androstenedione was a more active arogen regulator. Our results provide evidence that androgens play a critical role in the anabolic/androgenic regulation of GH and GH-binding proteins and that the androgen receptor is a critical target for their activity. Related Article:

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