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

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) x 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.