Two weeks of GH administration does not increase the expression of insulin-like growth factor-I mRNA splice variants in the skeletal muscles of young men

University of Nottingham (2004) J Physiol 558P, C4

Communications: Two weeks of GH administration does not increase the expression of insulin-like growth factor-I mRNA splice variants in the skeletal muscles of young men

Aperghis,Michael ; Hameed,Mahjabeen ; Bouloux,Pierre ; Goldspink,Geoffrey ; Harridge,Stephen ;

1. Surgery, Royal Free and University College Medical School, London, United Kingdom. 2. Endocrinology, Royal Free and University College Medical School, London, United Kingdom. 3. Physiology, Royal Free and University College Medical School, London, United Kingdom.

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Elevated growth hormone (GH) in blood leads to increased IGF-I derived from the liver. IGF-I is also expressed locally, particularly in skeletal muscle. However, the relationship between circulating GH and localised IGF-I mRNA expression in muscle is unclear. Recently, (Hameed et al. 2004) the mRNA levels of two splice variants of the IGI-I gene (IGF-IEa and MGF) were studied in muscle obtained from elderly males who were administering daily rhGH (0.5IU/m2/week for 5 weeks). IGF-IEa which is indistinct from mature liver-derived IGF-I, was significantly elevated, MGF remained unchanged. GH and IGF-I levels fall with increasing age but the effects of rhGH administration on young muscle are unknown. This is important as many athletes and bodybuilders use rhGH in an attempt to improve performance. The aim of this study was to examine the effects of exogenous rhGH on the expression of all three IGF-I mRNA splice variants (IGF-IEa, Eb and Ec) in adult males. With ethical approval, 8 healthy but untrained males (mean age 24.3) were recruited into a randomised double blind-with crossover trial. Subjects were randomly assigned to administering daily injections of rhGH (via subcutaneous injection 0.5IU/kg/week) or placebo for a 2-week period. Following 2 weeks washout, the groups were reversed. Following local anaesthesia (1% lignocaine), muscle biopsies were obtained at the end of each dosing phase from the vastus lateralis muscle. IGF-IEa, Eb and Ec (MGF) mRNA transcripts were analysed using real-time RT-PCR (Hameed et al 2004). Blood taken from the anticubital vein was analysed by ELISA for GH and mature IGF-1. The daily administration of rhGH resulted in a significant increase in circulating IGF-I and GH levels. However, no significant change in the mRNA of the three IGF-I transcripts was observed (Table 1). In apparent contrast to the muscles of older men who have lower GH levels, the muscles of young men remain unresponsive to rhGH administration in terms of IGF-I gene transcription.


Table 1Data are means ± S.E.M. mRNA is expressed as ng mRNA / mg total RNA. * Significant (P<0.05) rise in [IGF-I] detected as a result of GH administration compared to placebo at equivalent time points (Paired t-test).


Where applicable, experiments conform with Society ethical requirements.

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