The mRNA of two isoforms of the IGF-I gene has been shown to be expressed in human muscle. One, IGF-IEa, is similar to the systemic, liver-type IGF-I, whilst a second, MGF, is produced in muscle response to mechanical overload or damage. Recent studies of human muscle samples obtained shortly after a single bout of high-resistance exercise suggest that IGF-IEa and MGF mRNA transcripts are differentially regulated (Hameed et al. 2003). The present study was aimed at determining the effects of recombinant growth hormone (rhGH) administration with and without resistance training in elderly subjects on the mRNA expression of the two different isoforms of IGF-I.

Healthy elderly men (aged 74 ± 1 years, mean ± S.E.M.) were assigned to either resistance training (3 sessions/week, 3-5 sets of 8-12 repetition maximum per session) with placebo (RT group, n = 6), RT combined with rhGH administration (RT + GH group, n = 6) or rhGH alone (GH group, n = 7) in a randomised, placebo-controlled, double-blinded design (Lange et al. 2002). Administration of GH occurred daily through subcutaneous injection in the thigh (0.5 IU m^-2 rising to 1.5 IU m^-2). Following local anaesthesia (1 % lidocaine), muscle biopsies were obtained from the right vastus lateralis muscle at baseline, 5 weeks and 12 weeks. In the two training groups the biopsies were obtained 24 h after completion of the last training session. Samples were immediately frozen in liquid nitrogen. IGF-IEa and MGF mRNA transcripts were analysed using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method (LightCycler, Roche UK).

After 5 weeks of GH administration without exercise (GH), IGF-IEa had increased, by on average 226 %, in contrast to MGF mRNA levels, which were unchanged (Table 1). However, there was a significant increase in both IGF-1Ea (77 and 145 %) and MGF mRNA levels (200 and 354 %) in the RT and RT + GH groups, respectively, at this time point. A further 7 weeks of GH administration resulted in a significant increase in MGF (63 % relative to baseline), but no other significant changes in MGF or IGF-1Ea mRNA were observed between 5 and 12 weeks.

The results suggest that MGF mRNA expression in muscle is less sensitive to GH administration than IGF-IEa, at least in elderly subjects. However, when mechanical loading in the form of resistance training is combined with GH (RT + GH), both MGF and IGF-1Ea mRNA levels are enhanced, which may reflect an overall up-regulation of transcription of the IGF-I gene prior to splicing. Previously reported data from this study showed no greater increase in muscle strength and cross-sectional area with RT + GH compared with RT (Lange et al. 2002).

This work was supported by grants from WADA, European Union (Framework V-PENAM) and The Wellcome Trust.