A selective androgen receptor modulator with minimal prostate hypertrophic activity restores lean body mass in aged orchidectomized male rats
| Autor: | Zhihua Sui, Raymond A. Ng, Muh-Tsann Lai, Olivia Linton, Scott G. Lundeen, Sheela Bhattacharjee, George F. Allan, Tifanie Sbriscia, Donna Haynes-Johnson |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism Clinical Biochemistry Osteoporosis Drug Evaluation Preclinical Prostatic Hyperplasia Biology Models Biological Biochemistry Muscle hypertrophy Rats Sprague-Dawley Endocrinology Thinness Prostate Internal medicine Testis Androgen Receptor Antagonists medicine Animals Molecular Biology Wasting Cells Cultured Body Weight Age Factors Androgen Antagonists Organ Size Cell Biology medicine.disease Rats Androgen receptor medicine.anatomical_structure Selective androgen receptor modulator Androgens Body Composition Lean body mass Molecular Medicine Benzimidazoles medicine.symptom Orchiectomy Hormone |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 110:207-213 |
| ISSN: | 0960-0760 |
| Popis: | Androgens are required for the maintenance of normal sexual activity in adulthood and for enhancing muscle growth and lean body mass in adolescents and adults. Androgen receptor (AR) ligands with tissue selectivity (selective androgen receptor modulators, or SARMs) have potential for treating muscle wasting, hypogonadism of aging, osteoporosis, female sexual dysfunction, and other indications. JNJ-37654032 is a nonsteroidal AR ligand with mixed agonist and antagonist activity in androgen-responsive cell-based assays. It is an orally active SARM with muscle selectivity in orchidectomized rat models. It stimulated growth of the levator ani muscle with ED 50 0.8 mg/kg, stimulating maximal growth at a dose of 3 mg/kg. In contrast, it stimulated ventral prostate growth to 21% of its full size at 3 mg/kg. At the same time, JNJ-37654032 reduced prostate weight in intact rats by 47% at 3 mg/kg, while having no inhibitory effect on muscle. Using magnetic resonance imaging to monitor body composition, JNJ-37654032 restored about 20% of the lean body mass lost following orchidectomy in aged rats. JNJ-37654032 reduced follicle-stimulating hormone levels in orchidectomized rats and reduced testis size in intact rats. JNJ-37654032 is a potent prostate-sparing SARM with the potential for clinical benefit in muscle-wasting diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect