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Am J Physiol Endocrinol Metab (October 23, 2001). doi:10.1152/ajpendo.00191.2001
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Articles in PresS, published online ahead of print October 22, 2001
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00191.2001
Submitted on May 1, 2001
Accepted on October 5, 2001

ROLE OF IGF-1 AND IGF BINDING PROTEINS WITHIN DIAPHRAGM MUSCLE IN MODULATING THE EFFECTS OF NANDROLONE

Michael I Lewis1*, Gail D Horvitz2, David R Clemmons2, and Mario Fournier1

1 Medicine/Pulmonary Division, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, CA, USA
2 Medicine/Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

* To whom correspondence should be addressed. E-mail: michael.lewis{at}cshs.org.

Recent studies suggest that the anabolic effects of testosterone in muscle may in part be mediated by the insulin-like growth factor (IGF) system. The aim of this study was to examine the effects of nandrolone (NAN) on both IGF-1 and IGF binding proteins (BP) in the diaphragm muscle of one-year old female rats. NAN (6.6 mg/kg/day) was infused continuously for 17 days using a subcutaneous silastic implant, while controls (CTL) received blank capsules. Muscle fibers were classified immunohistochemically, and fiber cross-sectional areas (CSA) determined quantitatively. IGF-1 levels in both serum and muscle were determined by radioimmunoassay. Immunoreactivity to an IGF-1 antibody was used to localize IGF-1 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 to 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-1 in the diaphragm muscle were significantly higher (50%) in NAN treated animals. Immunohistochemistry revealed increased localization of IGF-1 within type IIx/b diaphragm fibers. In addition, NAN increased IGFBP-3 within the diaphragm (69%) while IGFBP-4 decreased (40%). We conclude that NAN-induced diaphragm muscle fiber hypertrophy is in part mediated 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.




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