Abstract
1088 Aging in men is associated with decreases in circulating GH, IGF-I and testosterone (T) levels, and in skeletal muscle mass and strength. The relationships among serum GH, IGF-I and sex steroids, and their corresponding activities within skeletal muscle, remain to be elucidated. We assessed spontaneous overnight GH secretion (log of integrated area under the secretory peaks; IAUPGH), basal AM serum IGF-I, IGFBP-3 and T levels, as well as lean body mass (LBM) and % body fat by DEXA in 44 healthy, community-dwelling older men (71.8 ± 0.7 y; mean ± SE). We then quantified mRNA levels for IGF-I receptor (IGF-Ir), GH receptor (GHr) and IGF-I in muscle biopsies from the dominant vastus lateralis using reverse transcriptase-polymerase chain reaction (RT-PCR). The relative expressions of the above transcripts were normalized to that of ribosomal 18s. There were no significant relationships of age, LBM, % body fat, log IAUPGH, serum IGF-I or IGFBP-3 with levels of muscle IGF-Ir, IGF-I, or GHr mRNA. In contrast, serum T was directly related to mRNA levels of IGF-Ir (r = 0.42, p = 0.005), and to a lesser extent, with those of GHr (r = 0.27, p = 0.05). Levels of GHr mRNA were directly related to those of both muscle IGF-I (r = 0.59, p = 0.001) and IGF-Ir (r = 0.34, p = 0.03), whereas there was no significant relationship between levels of IGF-Ir and IGF-I mRNA. Our findings that, in healthy elderly men, circulating T is directly related to skeletal muscle IGF-Ir and GHr mRNA levels suggests that androgen administration to andropausal elderly men stimulates skeletal muscle growth in part by modulating the autocrine/paracrine actions of GH and/or IGF-I. Moreover, the potential value of sex steroid administration in combination with recombinant human GH to further improve sarcopenia in elderly men and women deserves further investigation. Supported in part by NIH Grants: R01-AG11002-5 & T32-AG00250-01A1
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