The Role of PGF2a in Muscle Growth
After that brief introduction into prostaglandins, we can now begin to discuss more specifically the role of prostaglandins in muscle growth. In a nutshell, mechanical stimulation (i.e. intermittent stretch) results in the production and efflux of two prostaglandins, PGE2 and PGF2a. PGE2 increases protein degradation where as PGF2a increases protein synthesis. Muscle hypertrophy is usually achieved by an increase in protein synthesis as well as a proportionately smaller increase in degradation. The simultaneous release of both PGE2 and PGF2a creates this condition.
It is well known that mechanical stretch, without any electrical activity, is sufficient to induce muscle hypertrophy. Recent studies have shown that the mechanism by which mechanical stretch leads to prostaglandin production and ultimately muscle growth, involves G proteins embedded in the cell membrane. These G proteins increase the amount of cyclo-oxygenase, the enzyme responsible for making prostaglandins from arachidonic acid. Skeletal muscle cyclooxygenase generates PGE2 and PGF2 alpha at a ratio approximately equal to one.
The exact mechanism by which PGF2a increases protein synthesis is not entirely clear. That’s just a spineless way of saying, "I don’t know the exact answer to that!" We are free to speculate though. It may involve short phase protein synthesis and/or long phase protein synthesis.
2 phases of protein synthesis Modulation
Modulation of protein synthesis rates occurs at two levels, the short phase and the long phase. The short phase alteration in protein synthesis rates occurs by altering the activity of existing ribosomes and/or eukaryotic initiation factors (eIFs). This happens within minutes of the appropriate physiological trigger. The long phase modulation of protein synthesis happens by way of increasing the number of myonuclei. This mechanism involves hormones and growth factors such as HGH and IGF-1 bringing about the activation of myogenic stem cells. This can take several days to effect protein synthesis rates. This is a simplified view but for our purposes it is sufficient.
The role of PGF2a in short phase protein synthesis in muscle tissue is speculative at best. In non-muscle tissue, prostaglandins effect calcium fluxes, plasma membrane ionic channel activities, and cyclic nucleotide levels. All of which are important regulators of protein synthesis rates in muscle. PGF2a has been shown to interact with the S6 small ribosomal subunit, increasing its potential to form the ribosomal initiation complex with the large subunits. It is also plausible that PGF2a may effect the activity of eIFs.
Initiation of translation (the binding of mRNA to the ribosomal pre-initiation complex) requires group 4 eukaryotic initiation factors (eIFs). These initiation factors interact with the mRNA in such a way that makes translation (the construction of new proteins from the mRNA strand) possible. Two eIFs, called eIF4A and eIF4B, act in concert to unwind the mRNA strand. Another one called eIF4E binds to what is called the "cap region" and is important for controlling which mRNA strands are translated and also for stabilization of the mRNA strand. Finally, eIF4G is a large polypeptide that acts as a scaffold or framework around which all of these initiation factors and the mRNA and ribosome can be kept in place and proper orientation for translation. There is yet no direct evidence to confirm that PGF2a works through this mechanism however.
Long term modulation of protein synthesis involves the activation of myogenic stem cells or satellite cells. If you recall, when a muscle is stretched it not only produces PGF2a, but also PGE2. PGE2 is a potent inducer of satellite cell proliferation and fusion. This is how existing muscle cells increase the number of nuclei they contain. This is important because in order for a muscle to grow rapidly, it must produce more mRNA. This is done in the nucleus of the muscle cell. The more nuclei you have, the more mRNA you can produce. Within the cell, prostaglandins may also be involved in regulating the number of ribosomes. This could have long term implications on growth and development as well as stretch induced hypertrophy.