Role of IGF-I and IGF-binding proteins within diaphragm muscle in modulating the effects of nandrolone

Abstract

Recent studies suggest that the anabolic effects of testosterone in muscle may be mediated, in part, by the insulin-like growth factor (IGF) system. The aim of this study was to examine the effects of nandrolone (NAN) on both IGF-I and IGF-binding proteins (IGFBPs) in the diaphragm muscle of 1-yr-old female rats. NAN (6.6 mg · kg−1 · day−1) was infused continuously for 17 days using a subcutaneous Silastic implant, whereas controls (CTL) received blank capsules. Muscle fibers were classified immunohistochemically, and fiber cross-sectional areas (CSA) were determined quantitatively. IGF-I levels in both serum and muscle were determined by RIA. Immunoreactivity to an IGF-I antibody was used to localize IGF-I expression within individual muscle fibers. Muscle IGFBPs were determined by SDS-PAGE and Western ligand blotting and measured by scanning densitometry. Body weight was higher in the NAN group compared with CTL (9.4 ± 4.5% vs. −0.6 ± 3.1%). There were no changes in the fiber composition of the diaphragm. NAN increased the CSA of type IIa (20%) and type IIx/b (30%) diaphragm fibers. Levels of IGF-I in the diaphragm muscle were significantly higher (50%) in NAN-treated animals. Immunohistochemistry revealed increased localization of IGF-I within type IIx/b diaphragm fibers. In addition, NAN increased IGFBP-3 within the diaphragm (69%), whereas IGFBP-4 decreased (40%). We conclude that NAN-induced diaphragm muscle fiber hypertrophy is mediated, in part, by influences of the IGF system within the muscle, such that coordinated changes in IGFBPs reflect a direction of change that has been associated with an anabolic response in other test systems.

Androgen regulation of satellite cell function

“…In contrast, IGF-IEa was constitutively expressed in proliferation and differentiated C2C12 cells and was stimulated by a single ramp stretch but was reduced by repeated cycle stretch (Cheema et al 2005). Recent studies have suggested that the anabolic effects of androgens in muscle may be mediated, in part, by local IGF-I (Lewis et al 2002). In rats, the administration of nandrolone produced significantly higher levels of muscle IGF-I compared with rats without nandrolone treatment (Lewis et al 2002).…”

“…In recent years, it has become increasingly apparent that the autocrine/paracrine insulin-like growth factor (IGF) system within skeletal muscle plays an important role in myogenesis and maintenance of muscle fiber growth (Lewis et al 2002). IGF-I is ubiquitously expressed in skeletal muscle and appears to be important in both the proliferation and differentiation of skeletal muscle myoblasts (Florini et al 1996, Layne & Farmer 1999.…”

“…Recent studies have suggested that the anabolic effects of androgens in muscle may be mediated, in part, by local IGF-I (Lewis et al 2002). In rats, the administration of nandrolone produced significantly higher levels of muscle IGF-I compared with rats without nandrolone treatment (Lewis et al 2002). Androgen treatment was also found to increase IGF-I mRNA in bovine satellite cells (KamangaSollo et al 2004).…”

The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation

“…Testosterone acts as an anabolic signal in muscle and appears to exert its effects by increasing levels of IGF-I mRNA (42,56,119), Akt, Akt phosphorylation, and protein synthesis in muscle (114). Testosterone may also negatively regulate myostatin, since elevated myostatin levels are observed after castration in androgen-responsive muscle (68).…”

Modifying muscle mass – the endocrine perspective

“…In rat diaphragmatic muscle, a dosedependent increase in IGF-I mRNA expression occurred following exposure to androgen (Lewis et al 2002). When harvested bovine male satellite cells were treated with various androgen concentrations (using trenbolone), a dose-dependent increase in IGF-I mRNA expression occurred (Kamanga-Sollo et al 2004).…”