Impact of Androgens, Growth Hormone, and IGF‐I on Bone and Muscle in Male Mice During Puberty

• Published in: Journal of bone and mineral research 2007-01, Vol.22 (1), p.72-82
• Main Authors: Venken, Katrien, Movérare‐Skrtic, Sofia, Kopchick, John J, Coschigano, Karen T, Ohlsson, Claes, Boonen, Steven, Bouillon, Roger, Vanderschueren, Dirk
• Format: Article
• Language: English
• Subjects: Androgens; Androgens - pharmacology; Animals; Biological and medical sciences; Dihydrotestosterone; Dihydrotestosterone - pharmacology; drug effects; Fundamental and applied biological sciences. Psychology; Growth Hormone; Growth Hormone - pharmacology; growth hormone receptor gene disrupted or knockout mice; Insulin-Like Growth Factor I; Insulin-Like Growth Factor I - pharmacology; Male; MEDICAL AND HEALTH SCIENCES; MEDICIN OCH HÄLSOVETENSKAP; Mice; muscle mass; orchidectomy; Orchiectomy; periosteal bone; pharmacology; physiology; puberty; Receptors; Receptors, Somatotropin - drug effects; Receptors, Somatotropin - physiology; Sexual Maturation; Sexual Maturation - drug effects; Sexual Maturation - physiology; Skeleton and joints; Somatotropin; Testosterone; Testosterone - pharmacology; trabecular bone; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.060911

The interaction between androgens and GH/IGF‐I was studied in male GHR gene disrupted or GHRKO and WT mice during puberty. Androgens stimulate trabecular and cortical bone modeling and increase muscle mass even in the absence of a functional GHR. GHR activation seems to be the main determinant of radial bone expansion, although GH and androgens are both necessary for optimal stimulation of periosteal growth during puberty. The interaction between androgens and GH/IGF‐I was studied in male GHR gene disrupted or GHRKO and WT mice during puberty. Androgens stimulate trabecular and cortical bone modeling and increase muscle mass even in the absence of a functional GHR. GHR activation seems to be the main determinant of radial bone expansion, although GH and androgens are both necessary for optimal stimulation of periosteal growth during puberty. Introduction: Growth hormone (GH) is considered to be a major regulator of postnatal skeletal growth, whereas androgens are considered to be a key regulator of male periosteal bone expansion. Moreover, both androgens and GH are essential for the increase in muscle mass during male puberty. Deficiency or resistance to either GH or androgens impairs bone modeling and decreases muscle mass. The aim of the study was to investigate androgen action on bone and muscle during puberty in the presence and absence of a functional GH/insulin‐like growth factor (IGF)‐I axis. Materials and Methods: Dihydrotestosterone (DHT) or testosterone (T) were administered to orchidectomized (ORX) male GH receptor gene knockout (GHRKO) and corresponding wildtype (WT) mice during late puberty (6–10 weeks of age). Trabecular and cortical bone modeling, cortical strength, body composition, IGF‐I in serum, and its expression in liver, muscle, and bone were studied by histomorphometry, pQCT, DXA, radioimmunoassay and RT‐PCR, respectively. Results: GH receptor (GHR) inactivation and low serum IGF‐I did not affect trabecular bone modeling, because trabecular BMD, bone volume, number, width, and bone turnover were similar in GHRKO and WT mice. The normal trabecular phenotype in GHRKO mice was paralleled by a normal expression of skeletal IGF‐I mRNA. ORX decreased trabecular bone volume significantly and to a similar extent in GHRKO and WT mice, whereas DHT and T administration fully prevented trabecular bone loss. Moreover, DHT and T stimulated periosteal bone formation, not only in WT (+100% and +100%, respectively, versus ORX + vehicle [V]; p < 0.05)