Jasuja, R., Ramaraj, P., Mac, R.P., Singh, A.B., Storer, T.W., Artaza, J.N., Miller, A., Singh, R., Taylor, W.E., Lee, M.L., Davidson, T., Sinha-Hikim, I., Gonzalez-Cadavid, N. and Bhasin, S. (2005) Δ-4-Androstene-3,17-Dione Binds Androgen Receptor, Promotes Myogenesis in Vitro and Increases Serum Testosterone Levels, Fat-Free Mass, and Muscle Strength in Hypogonadal Men. The Journal of Clinical Endocrinology & Metabolism, 90, 855-863. http://dx.doi.org/10.1210/jc.2004-1577

has been cited by the following article:

• TITLE: Effect of Androstenedione on Adipogenesis in Murine C3H10T1/2 Mesenchymal Cells

  AUTHORS: Pandurangan Ramaraj, Jorge N. Artaza, Indrani Sinha-Hikim, Wayne E. Taylor

  KEYWORDS: Androstenedione, Adipogenesis, Myogenesis, Androgen Receptor, Bicalutamide

  JOURNAL NAME: Open Journal of Endocrine and Metabolic Diseases, Vol.5 No.2, February 9, 2015

  ABSTRACT: Clinical trials of weak androgen androstenedione (AD) administered at a high concentration, showed an increase in muscle mass in men like strong androgens testosterone (T) and dihydrotestosterone (DHT), but did not show any inhibitory effect on fat mass unlike strong androgens. This observation prompted us to check the in-vitro effect of AD on adipogenesis using mouse mesenchymal multipotent cells (C3H10T1/2), which can differentiate into both myoblasts and adipocytes. Results indicated that AD inhibited adipogenesis at 10 nM, 100 nM and 1 μM concentrations, but not at 10 μM concentration. AD did not inhibit adipogenesis at 10 μM concentration and also did not inhibitmyogenesis at 10 μM concentration. Addition of bicalutamide, an androgen receptor (AR) antagonist decreased myogenesis and increased adipogenesis, indicating that the effect of AD was mediated through AR. Another weak androgen dehydroepiandrosterone (DHEA) also showed the same pattern of adipogenesis in 10T1/2 cells. AD also showed a similar pattern of adipogenesis in 3T3-L1 preadipocyte cells. Thus, the in-vitro results of AD on adipogenesis correlated with the in-vivo results of AD on fat-mass from clinical trials and suggested a possible difference in biological action between weak androgens (AD, DHEA) and strong androgens (T, DHT) on adipogenesis. Since the biological action of AD was mediated through AR, this physiological difference onadipogenesis could be due to the nature (partial agonist/antagonist) of AD binding to AR.