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Tissue Selectivity of the Anabolic Steroid, 19-Nor-4-Androstenediol-3{beta},17{beta}-diol in Male Sprague Dawley Rats: Selective Stimulation of Muscle Mass and Bone Mineral Density Relative to Prostate Mass.Page ST, Marck BT, Tolliver JM, Matsumoto AM.
Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States, 98195; Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States, 98108 and Office of Diversion Control, Drug Enforcement Administration, Department of Justice, Arlington, VA, United States, 22202.
Stimulation of prostate growth is a major concern with testosterone therapy in older hypogonadal men. As a result, non-steroidal selective androgen receptor modulators (SARMs) with anabolic activity but less prostate stimulation are being developed. Anabolic steroids might exhibit similar tissue selectivity. We hypothesized the anabolic steroid 19-nor-4-androstenediol-3beta,17beta-diol (3beta,19-NA)) would increase muscle, lean body mass (LBM), and bone mineral density (BMD) with little stimulation of prostate growth. Male Sprague Dawley rats were implanted with silastic capsules containing 3beta,19-NA (4,8 or 16 cm), dihydrotestosterone (DHT) (8cm), 19-nortestosterone (19-NT) (16cm) or four empty capsules after undergoing either a sham-operation (Intact) or orchidectomy (ORX). Serum gonadotropins, measured after 4, 8 or 24 weeks of treatment, were significantly lower in 3beta,19-NA-treated versus untreated, intact and ORX rats (P<0.05), and testosterone was lowered by 3beta,19-NA-treatment of intact animals. LBM and BMD were assessed after 20 weeks, and 4 weeks later rats were sacrificed for levator ani muscle (LA) and prostate weights. Compared to ORX rats, 3beta,19-NA-treated rats had dose-dependent higher LA weights, LBM and BMD, which were similar to intact and DHT-treated rats at the highest 3beta,19-NA dose. In contrast, prostate weights in all 3beta,19-NA-treated groups were similar to ORX rats and lower than intact, DHT- and 19-NT-treated rats even at the highest 3beta,19-NA dose. In summary, 3beta,19-NA increases muscle and bone mass without significant stimulation of prostate growth, suggesting it may have some properties of a steroidal SARM. Anabolic steroids such as 3beta,19-NA should be studied further to determine their mechanisms of tissue selectivity and effects in men.
PMID: 18096666 [PubMed - as supplied by publisher]
Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States, 98195; Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States, 98108 and Office of Diversion Control, Drug Enforcement Administration, Department of Justice, Arlington, VA, United States, 22202.
Stimulation of prostate growth is a major concern with testosterone therapy in older hypogonadal men. As a result, non-steroidal selective androgen receptor modulators (SARMs) with anabolic activity but less prostate stimulation are being developed. Anabolic steroids might exhibit similar tissue selectivity. We hypothesized the anabolic steroid 19-nor-4-androstenediol-3beta,17beta-diol (3beta,19-NA)) would increase muscle, lean body mass (LBM), and bone mineral density (BMD) with little stimulation of prostate growth. Male Sprague Dawley rats were implanted with silastic capsules containing 3beta,19-NA (4,8 or 16 cm), dihydrotestosterone (DHT) (8cm), 19-nortestosterone (19-NT) (16cm) or four empty capsules after undergoing either a sham-operation (Intact) or orchidectomy (ORX). Serum gonadotropins, measured after 4, 8 or 24 weeks of treatment, were significantly lower in 3beta,19-NA-treated versus untreated, intact and ORX rats (P<0.05), and testosterone was lowered by 3beta,19-NA-treatment of intact animals. LBM and BMD were assessed after 20 weeks, and 4 weeks later rats were sacrificed for levator ani muscle (LA) and prostate weights. Compared to ORX rats, 3beta,19-NA-treated rats had dose-dependent higher LA weights, LBM and BMD, which were similar to intact and DHT-treated rats at the highest 3beta,19-NA dose. In contrast, prostate weights in all 3beta,19-NA-treated groups were similar to ORX rats and lower than intact, DHT- and 19-NT-treated rats even at the highest 3beta,19-NA dose. In summary, 3beta,19-NA increases muscle and bone mass without significant stimulation of prostate growth, suggesting it may have some properties of a steroidal SARM. Anabolic steroids such as 3beta,19-NA should be studied further to determine their mechanisms of tissue selectivity and effects in men.
PMID: 18096666 [PubMed - as supplied by publisher]
