The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men

Abstract

The expression of two isoforms of insulin-like growth factor-I (IGF-I): mechano growth factor (MGF) and IGF-IEa were studied in muscle in response to growth hormone (GH) administration with and without resistance training in healthy elderly men. A third isoform, IGF-IEb was also investigated in response to resistance training only. The subjects (age 74 +/- 1 years, mean +/- S.E.M) were assigned to either resistance training with placebo, resistance training combined with GH administration or GH administration alone. Real-time quantitative RT-PCR was used to determine mRNA levels in biopsies from the vastus lateralis muscle at baseline, after 5 and 12 weeks in the three groups. GH administration did not change MGF mRNA at 5 weeks, but significantly increased IGF-IEa mRNA (237%). After 12 weeks, MGF mRNA was significantly increased (80%) compared to baseline. Five weeks of resistance training significantly increased the mRNA expression of MGF (163%), IGF-IEa (68%) and IGF-IEb (75%). No further changes were observed after 12 weeks. However, after 5 weeks of training combined with GH treatment, MGF mRNA increased significantly (456%) and IGF-IEa mRNA by (167%). No further significant changes were noted at 12 weeks. The data suggest that when mechanical loading in the form of resistance training is combined with GH, MGF mRNA levels are enhanced. This may reflect an overall up-regulation of transcription of the IGF-I gene prior to splicing.

Figure 1. Schematic representation of the human IGF-I gene and its splice variants expressed in muscle

The black box denotes the insert in exon 5 (49 bp), which gives rise to the alternatively spliced MGF isoform (adapted from Hameed et al. 2002).

Figure 2. Changes in MGF and IGF-IEa mRNA levels in elderly men in the three groups: GH, RT and RT + GH

Values are expressed as a percentage change from baseline at 5 (grey bars) and 12 (black bars) weeks. Bars and error bars represent mean values and s.e.m, respectively. * Significant difference from baseline; ^#significant difference from from 5 weeks (P < 0.05); † significant difference in percentage change between isoforms (P < 0.05).

Figure 2. Changes in MGF and IGF-IEa mRNA levels in elderly men in the three groups: GH, RT and RT + GH

Values are expressed as a percentage change from baseline at 5 (grey bars) and 12 (black bars) weeks. Bars and error bars represent mean values and s.e.m, respectively. * Significant difference from baseline; ^#significant difference from from 5 weeks (P < 0.05); † significant difference in percentage change between isoforms (P < 0.05).

Figure 3. The change in IGF-IEb mRNA levels after RT

Values are expressed as ng of mRNA per μg total RNA (mean + s.e.m). *Significant difference from baseline; ^#significant difference from 5 weeks (P < 0.01).

Figure 4. Relationship between the change in serum IGF-I levels and the change in muscle IGF-IEa (A) and MGF (B) mRNA

There was a significant correlation (r = 0.81, P < 0.05) between serum IGF-I levels and IGF-IEa mRNA in muscle after 12 weeks of GH administration alone (A). After 12 weeks of GH combined with RT, there was a significant correlation (r = 0.83, P < 0.05) between serum IGF-I levels and MGF mRNA in muscle (B).

Figure 5. Relationship between baseline levels of MGF mRNA and muscle CSA

Significantly higher levels of MGF and IGF-IEa mRNA were observed in the GH only group. Linear regression studies showed a significant correlation between baseline levels of MGF and muscle CSA (r = 0.582, P < 0.01).