CLARIFICATION

Abstract

Journal of Physiology547, 247–254 (2003)

We were pleased to see that our article was the subject of a Perspective (Spangenburg, 2003)in a recent issue of the Journal of Physiology. Unfortunately, there are some errors in the Perspective which may cause further confusion concerning the nomenclature of the different IGF-I isoforms, perpetuating a confusion which already exists in the literature.This is also important as it becomes clearer that the different isoforms may have different physiological roles.

On the basis of their mRNA transcripts, three isoforms have thus far been identified in human skeletal muscle. These have been termed ‘IGF-IEa’, ‘IGF-IEb’ and ‘IGF-IEc’ based on isoforms detected in hepatic cells including neoplasms (Rotwein et al. 1986; Chew et al. 1995). It is the IGF-IEc and not the IGF-IEb isoform that has been termed ‘mechano-growth factor’ (MGF)in human muscle and reported in our recent study (Hameed et al. 2003). It differs from the IGF-IEa isoform by the inclusion of a 49 base pair sequence from exon 5.

In overloaded animal muscle there are two clearly identified transcripts, IGF-IEa and IGF-IEb. In this case, IGF-IEb has been termed MGF (Yang et al. 1996). Here, IGF-IEb, or MGF in animal muscle, differs slightly from the human MGF sequence as it contains a 52 base pair insert in exon 5. Other terms have also been used to describe the different isoforms. For example, Musaro et al. (2001), who overexpressed IGF-I in the muscles of transgenic mice, termed it ‘m.IGF-I’. This is not MGF, but in fact corresponds to the IGF-IEa isoform, which is expressed in most tissues as well as in muscle.

The third isoform which occurs in human muscle is rather confusingly termed IGF-IEb. This includes exon 5 but not exon 6. It is thus a separate isoform and is therefore not MGF, as implied in the Perspective.

It is clear that there is considerable confusion about the IGF-I nomenclature and some uniformity of terms is now needed to clarify the situation. For this reason we refer to the mechanosensitive splice variant (IGF-IEc)of the human as mechano-growth factor (MGF), as this relates to its physiological role.