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1 Division of Pulmonary/Critical Care Medicine, The Burns and Allen Research Institute, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California 90048; and 2 Division of Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
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 · day1) 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.
anabolic steroids; autocrine/paracrine effects; insulin-like growth factor I; insulin-like growth factor-binding proteins; muscle fiber hypertrophy; respiratory muscles
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