About Myostatin:
Myostatin (also known as growth differentiation factor 8 and often abbreviated to GDF-8) is a myokine, a protein that is produced and released by myocytes that act on the autocrine functions of muscle cells to inhibit muscle cell growth and differentiation. In humans, it is encoded by the MSTN gene. Myostatin is a secreted growth differentiation factor that is a part of the TGF beta protein group.
When lacking in myostatin or treated with something that blocks the activity of myostatin, subjects have significantly more muscle mass. Furthermore, subjects that have mutations in both copies of the myostatin gene have both significantly more muscle mass in addition to being stronger than normal. Studies into myostatin could potentially find treatments for muscle wasting diseases such as muscular dystrophy.
Mechanism of Action
Myostatin is inactive until a protease cleaves the NH2-terminal, or “pro-domain” portion of the molecule. This results in the active COOH-terminal dimer. Myostatin binds to the activin type II receptor, resulting in the recruitment of coreceptor Alk-3 or Alk-4. The coreceptor then initiates a cell signalling cascade in the muscle which includes the activation of transcription factors in the SMAD family, SMAD2 and SMAD3. These factors then induce myostatin-specific gene regulation.
Myostatin also inhibits Akt which is a kinase that is sufficient to cause muscle hypertrophy. This is achieved partially through the activation of protein synthesis. However, Akt is not entirely responsible for all of the muscle hypertrophic effects which have been observed. As a result, myostatin has two primary mechanisms: inhibiting muscle differentiation and inhibiting Akt-induced protein synthesis.
Structure
Human myostatin consists of two identical subunits that are made from 109 amino acid residues. The total molecular weight is 25.0 kDa.
Clinical Significance
In 2004, a German boy was found to have a mutation in both copies of the myostatin-producing gene. This made him considerably stronger than other boys around his age. His mother was found to also have a mutation in one copy of the gene.
An American boy born in 2005 was diagnosed with a similar condition but with a different cause. Instead of having a mutation in copies of his myostatin-producing gene, he produced a regular level of functional myostatin. Instead, a defect in his myostatin receptors is thought to prevent his muscle cells from responding normally to myostatin. This causes him to have greater strength and muscle mass than others around his age.
Further research into myostatin and its associated gene may eventually lead to therapies for muscular dystrophy by introducing substances that block myostatin. A monoclonal antibody specific to myostatin has shown to increase muscle mass in mice and monkey. It’s uncertain if long-term treatment of muscular dystrophy with myostatin inhibitors is beneficial due to the depletion of muscle stem cells that could worsen the condition. As of now, there are no myostatin-inhibiting drugs available for humans.