Serum IGF-I levels and IGF-I gene splicing in muscle of healthy young males receiving rhGH.
OBJECTIVE
Elevated growth hormone (GH) levels lead to increased circulating insulin-like growth factor-I (IGF-I), but the effects on localised muscle IGF-I splice variant expression is not known. The effects of rhGH administration, with or without an acute bout of high resistance exercise, were measured on serum IGF-I and on the mRNA levels of IGF-I splice variants in the vastus lateralis muscle of healthy young men.


METHODS
The study was a randomised double blind trial with a crossover design. Seven subjects were randomly assigned to a group receiving daily injections of rhGH (0.075IU kg(-1)day(-1)) or placebo for a two week period. Following a one month washout, the groups were reversed.


RESULTS
Administration of rhGH increased circulating IGF-I from 31.8+/-3.2 to 109+/-5.4 nmol/L (p<0.05). There was no effect of the exercise bout. RNA was extracted from muscle biopsies obtained from exercised and non-exercised legs 2.5h after the cessation of the exercise. Transcript expression was measured using Real-time QPCR. There was no effect of either exercise or rhGH administration on IGF-I 5' (Class 1 or Class 2) or 3' (IGF-IEa, or MGF) transcripts.


CONCLUSIONS
Although rhGH administration has an effect on liver IGF-I expression, as shown by increase in circulating IGF-I, muscle IGF-I expression is unaffected in young healthy subjects with normal GH profile. The findings contrast with those of a previous study in which GH deficient elderly men showed higher muscle IGF-I 3' splice variant levels following rhGH administration with and without resistance training. Unlike in the liver, muscle Class1 and 2 IGF-I expression do not change significantly following administration of rhGH.
Aperghis
Michael
M
Department of Surgery, University College London, Hampstead Campus, London, UK.
Velloso
Cristiana P
CP
Hameed
Mahjabeen
M
Brothwood
Theresa
T
Bradley
Lloyd
L
Bouloux
Pierre M G
PM
Harridge
Stephen D R
SD
Goldspink
Geoffrey
G
D000328:Adult; D017398:Alternative Splicing; D015444:Exercise; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use; D055815:Young Adult
D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I