Myostatin Expression & PE
Hey all, long-time but first time poster here. I’ve been into PE for a while now, but have recently found myself rather curious about the field of Chem PE. I’ve been trying to gather as much info about it, look into some things that haven’t been discussed as frequently as others, and just generally learn all about it.
During one of my many quests for knowledge recently, I came across some posts elsewhere that briefly touched on Myostatin and whether or not Myostatin expresses in penile tissues. Myostatin is a protein that essentially stops growth. People and animals lacking Myostatin experience very significant muscle growth. I haven’t looked into Myostatin itself much, so my apologies for the simple definition.
Anyways, as for Myostatin and the penis, after some searching around, I found a patent that touches on just that.It’s a bit of a long read and contains mostly complex chemistry. Although the whole thing doesn’t focus on PE, there’s many parts that touch on using Myostatin inhibitors/antibodies to treat a various array of penile conditions, specifically mentioning enlargement.
I’ve never seen this mentioned before, aside from very briefly on another board where the idea was brought up in the first place. I was thinking it would be nice to get a discussion going about it. Not sure how likely it is to use these methods in reality though. Perhaps someone more knowledgeable on the subject than myself can chime in and make better sense of this better than I can. My apologies if this is less ChemPE/PE related than it actually appears, I’m not the greatest when it comes to chemistry, but I found this interesting and figured it was worth posting about.
The patent can be read here: https://www.google.com/patents/US8426374
If it’s okay, I’ll post some PE-related excerpts below.
In one study, injections of a protease resistant propeptide form of myostatin, which cannot be processed into the putative mature myostatin but can bind the one already produced, were administered weekly over the period of one month. As a result of the weekly injections, muscle mass increased by 25 percent.
In another study, daily injections of anti-myostatin antibodies were administered into the peritoneum for one month <b>resulting in a muscle mass increase of 20%</b>.
Methods may include those which directly block myostatin expression and/or its activity using agents which may include, but are not limited to antibodies against myostatin, proteins that bind to and inhibit myostatin activity and/or their encoding cDNAs, inhibiting peptides and/or their encoding cDNAs, shRNA targeting myostatin, siRNA targeting myostatin, agents that inhibit the expression of myostatin, agents that inhibit the activity of myostatin, or ligands that bind to the myostatin/activin receptor. Additional methods may include, but are not limited to, modulating the expression or activity of proteins and/or mucopolysaccharides that regulate the activity of myostatin. Modulation could include antibodies against these myostatin regulating proteins, proteins that bind to and modulate the regulatory protein activity, inhibiting peptides, shRNA, siRNA, inhibitor or activator agents that block or enhance the expression of the myostatin regulating proteins, agents that modulate the activity of myostatin regulating proteins. Examples may include increasing the expression or activity of follistatin or related proteins, or administering it directly.
In some embodiments, the method of inhibiting myostatin expression and/or activity may include local inhibition of myostatin by delivering an agent at a point within the tissue region where myostatin inhibition is desired. In other embodiments, the method of inhibiting myostatin expression and/or activity may include systemic inhibition of myostatin by delivering an agent to a tissue near (e.g., proximal to) the tissue region where myostatin inhibition is desired or delivering the treatment agent more remotely.
Therapeutic uses may include, but are not limited to, the enlargement of penis size, or in the treatment or prevention of small penis size, cavernosal smooth muscle myopathies, congenital micropenis and other genetic abnormalities, effects of hypogonadism on penile size, penile trauma, hypospadias, transsexual penile construction, penile amputation, penile cancer, Peyronie\’s disease and vasculogenic erectile dysfunction related to penile fibrosis.
Loss of myostatin mRNA leads to a decrease in myostatin protein, which in turn leads to increased inhibition of myostatin activity. This inhibition of myostatin activity, results in increased muscle cell mass (hypertrophy) and it is further believed myostatin inhibition results in increased muscle cell number (hyperplasia). In one embodiment, the target cell may be that of any mammalian tissue which may be regulated or otherwise modified by myostatin expression. In one aspect, the target cell may be that of a skeletal muscle tissue. In other embodiments, the target cell may be that of a smooth muscle tissue, such as, for example, smooth muscle of the corpora cavernosa of the penis.
1. Myostatin is a Growth Inhibitor and Pro-Fibrotic Factor in the Smooth Muscle, and Counteracting it Stimulates Smooth Muscle Proliferation Thus Increasing Penile Size and Preventing Fibrosis.
Although myostatin has been previously shown to be expressed in skeletal muscle tissue, embodiments and results which will now be described are the first to demonstrate that myostatin is also expressed in smooth muscle, specifically in the penile corpora cavernosa. In particular, myostatin expression may be found in both the corpora cavernosa (primarily smooth muscle) and in the tunica albuginea (primarily fibroblasts and myofibroblasts).
Since myostatin inhibits cell growth and we have found that it is expressed in smooth muscle cells, this suggests that it acts as a smooth muscle cell growth inhibitor, that is blocking cell replication. Considering that smooth muscle is the bulk of the penile shaft, we believe that blocking myostatin expression and/or activity will increase penile corpora cavernosa size, that is penile size.
FIG. 10 illustrates average penile weight for R-shRNA and Mst-shRNA treated samples (*p<0.05). In this aspect, increase in penile weight is correlated with injection of myostatin shRNA plasmid. Rat penis may be injected with 100 μg of either the pSILENCER® 2.1-U6 neo-myostatin siRNA plasmid construct or pSILENCER® 2.1-U6 neo-randomer plasmid and electroporated in a manner identical to that done for skeletal muscle (n=2, R-shRNA group; n=3, Mst-shRNA group) as previously discussed. After two weeks, the penises may be harvested and weighed. As shown in FIG. 10, penile weight increases on average by 16.8% in Mst-shRNA treated penises as compared to R-shRNA treated penises.
The combined in vitro and in vivo results shown above indicate that myostatin is expressed in smooth muscle cells, and <b>it is therefore believed that blocking myostatin may increase penile size such as by an increase in smooth muscle cell proliferation</b>. Such results would have a variety of applications, including for example, penile compliance, e.g., rigidity during erection may be increased too. Moreover myostatin expression in the penile tunical fibroblasts intensifies in a fibrotic process of the tunica, Peyronie's disease, and that it is expressed in the cells responsible for the fibrotic process: the myofibroblasts.
In view of the foregoing, it is believed that blocking myostatin expression by shRNA or any other procedure, or <b>inhibiting myostatin activity, may increase smooth muscle content in the penis and penile size, and counteract fibrosis, thus improving erectile function and counteracting impotence associated with penile fibrosis.[/b] In more general terms, the same process may counteract fibrosis in the skeletal muscle and other tissues.
In view of the foregoing, it is believed that inhibiting myostatin expression and/or activity, in addition to preventing skeletal muscle loss or inducing an increase in skeletal muscle mass, may be used therapeutically for: a) increasing penile smooth muscle content and size; b) increase smooth muscle content in other organs; and c) prevent fibrosis.
Exemplary penile conditions that can be treated by this approach may include, but are not limited to enlargement of penis size, or in the treatment or prevention of small penis size, cavernosal smooth muscle myopathies, congenital micropenis and other genetic abnormalities, effects of hypogonadism on penile size, penile trauma, hypospadias, transsexual penile construction, penile amputation, penile cancer, Peyronie's disease, vasculogenic erectile dysfunction related to penile fibrosis.
12. A method for treating a penile condition comprising:
Delivering a composition to a myostatin expressing penile tissue found in one of a corpora cavernosa or a tunica albuginea region of a penis, the composition comprising a vector having a nucleotide sequence expressed as a shRNA having a property to inhibit myostatin expression, wherein the vector including the nucleotide sequence is present in an amount sufficient to treat a penile condition.
13. The method of claim 12 wherein treating the penile condition comprises increasing a mass of the myostatin expressing penile tissue.
14. The method of claim 12 wherein treating the penile condition comprises counteracting fibrosis.
15. The method of claim 12 wherein the myostatin expressing tissue is a penile smooth muscle tissue found in the corpora cavernosa.
16. The method of claim 12 wherein the myostatin expressing tissue is a fibroblast or a myofibroblast found in the tunica albuginea.