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Dr Pangloss
04-16-2009, 06:18 PM
The following may be the answer (tentatively). this report on myostatin (a powerful muscle growth inhibitor) shows that after 8 weeks on Testoterone, myostatin levels rise significantly. Fortunately it's dependent on Testosterone levels and not muscle mass. When you stop the Test, myostatin levels go back to normal....

8-10 weeks is when the gains from a cycle peeter out. Wish i had some solutble activinIIB receptor or myo-29 antibody to knock that shit off....:rolleyes:


: Mol Cell Endocrinol. (javascript:AL_get(this, 'jour', 'Mol Cell Endocrinol.');) 2009 Apr 10;302(1):26-32. Epub 2009 Jan 21.http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif (http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=19356623&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0303-7207(09)00026-4) Links (javascript:PopUpMenu2_Set(Menu19356623);)

Measurement of myostatin concentrations in human serum: Circulating concentrations in young and older men and effects of testosterone administration.

Lakshman KM (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lakshman%20KM%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Bhasin S (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Bhasin%20S%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Corcoran C (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Corcoran%20C%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Collins-Racie LA (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Collins-Racie%20LA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Tchistiakova L (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Tchistiakova%20L%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Forlow SB (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Forlow%20SB%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), St Ledger K (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22St%20Ledger%20K%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Burczynski ME (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Burczynski%20ME%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Dorner AJ (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Dorner%20AJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Lavallie ER (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lavallie%20ER%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).
Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston Medical Center, 670 Albany Street, Boston, MA 02118, United States.
Methodological problems, including binding of myostatin to plasma proteins and cross-reactivity of assay reagents with other proteins, have confounded myostatin measurements. Here we describe development of an accurate assay for measuring myostatin concentrations in humans. Monoclonal antibodies that bind to distinct regions of myostatin served as capture and detector antibodies in a sandwich ELISA that used acid treatment to dissociate myostatin from binding proteins. Serum from myostatin-deficient Belgian Blue cattle was used as matrix and recombinant human myostatin as standard. The quantitative range was 0.15-37.50 ng/mL. Intra- and inter-assay CVs in low, mid, and high range were 4.1%, 4.7%, and 7.2%, and 3.9%, 1.6%, and 5.2%, respectively. Myostatin protein was undetectable in sera of Belgian Blue cattle and myostatin knockout mice. Recovery in spiked sera approximated 100%. ActRIIB-Fc or anti-myostatin antibody MYO-029 had no effect on myostatin measurements when assayed at pH 2.5. Myostatin levels were higher in young than older men (mean+/-S.E.M. 8.0+/-0.3 ng/mL vs. 7.0+/-0.4 ng/mL, P=0.03). In men treated with graded doses of testosterone, myostatin levels were significantly higher on day 56 than baseline in both young and older men; changes in myostatin levels were significantly correlated with changes in total and free testosterone in young men. Myostatin levels were not significantly associated with lean body mass in either young or older men. CONCLUSION: Myostatin ELISA has the characteristics of a valid assay: nearly 100% recovery, excellent precision, accuracy, and sufficient sensitivity to enable measurement of myostatin concentrations in men and women.
PMID: 19356623 [PubMed - in process]

thepump
04-16-2009, 06:54 PM
:popcorn:good read.

Dr Pangloss
04-16-2009, 07:02 PM
The Test level used was a range and includes 300-600 mg ew of Test Enanthate.

young group is to 35 i think.

Old group is 60-75.

Older folks showed higher levels of myostatin at the start and they did not change with Test, which suggests that myostatin becomes constitutively elevated...

This is a great drug target. The next ten years with drugs directed at myostatin and its receptors will change bodybuilding radically.

Tatyana
04-16-2009, 07:04 PM
Do you have any papers on myostatin polymorphisms and the distribution in the population?

Dr Pangloss
04-16-2009, 07:06 PM
Do you have any papers on myostatin polymorphisms and the distribution in the population?


they are out there. mutants anyway. I dont think the ones that block myostatin expression or activity rise to the level of "polymorphism" per se. I think they remain very low frequency familial mutations.

There are, of course, cattle that carry this mutation. The Belgian Blue is one.

as far as expression level altering polymorphisms in humans or polymorphisms that reduce/enhance myostating function, i have not seen any yet...

if you run into one, please post in this forum.

this is the most potentially exciting target for bodybuilders in the last 60 years...

Tatyana
04-16-2009, 07:13 PM
I am refering to more subtle variations.

For example, there are what they refer to as long and short forms of serotonine transporters, and these confer a variability in the re-uptake of serotonin.

These sorts of polymorphisms exist for nearly every enzyme system in the body, so for example if you have a hyper functioning follistatin manufacturing system, and a less effective myostatin making enzyme, voila, lower levels of myostatin, more muscle.

I am sleep deprived and not sure if I am getting my point across. :)

Dr Pangloss
04-16-2009, 07:15 PM
I can check for spice-variants. There can also be multiple alleles with myostatin homologs. I dont' think there are for myostatin per se, but it is a member of the tgf-beta superfamily, which include a zillion growth factors/modulators.


You're talking about splice variants, i believe. It is estimated that as many as 40-50% of the genes in the human genome have splice variants. These splice variats add or subtract pieces of protein with specific subfunctions. It's a really beautiful way to diversify a protein...


i believe i gotcha. I will check.

Tatyana
04-16-2009, 07:37 PM
Titre du document / Document title

Mechanisms involved in the inhibition of myoblast proliferation and differentiation by myostatin
Auteur(s) / Author(s)

JOULIA Dominique ; BERNARDI Henri ; GARANDEL Véronique ; RABENOELINA Fanjaniriana ; VERNUS Barbara ; CABELLO Gérard ;
Résumé / Abstract

Muscle growth results from a set of complex processes including myogenic transcription factor's expression and activity, cell cycle withdrawal, myoblast fusion in myotubes, and acquisition of an apoptosis-resistant phenotype.

Myostatin, a member of the TGFβ family, described as a strong regulator of myogenesis in vivo Nature 387 (1997), 83; FEBS Lett. 474 (2000), 71 is upregulated during in vitro differentiation Biochem. Biophys. Res. Commun. 280 (2001), 561.

To improve characterization of myostatin's myogenic influence, we stably transfected vectors expressing myostatin and myostatin antisense in C2C12 myoblasts.

Here, we found that myostatin inhibits cell proliferation and differentiation. Our results also indicate that myogenin is an important target of myostatin.

In addition, overexpressed but not endogenous myostatin decreases MyoD protein levels and induces changes in its phosphorylation pattern.

We also established that myostatin overexpression reduces the frequency of G0/GI-arrested cells during differentiation.

Conversely, inhibition of myostatin synthesis leads to enhanced cell cycle withdrawal and consequently stimulates myoblast differentiation. We examined the expression patterns of the pRb, E2F1, p53, and p21 proteins involved in cell cycle withdrawal.

We found that myostatin overexpression increases p21 and p53 expression, as it does accumulation of hypophosphorylated Rb. Interestingly, myostatin overexpression strongly reduced low-mitogeninduced apoptosis, whereas antisense expression induced contrary changes.

In conclusion, these data show the influence of overexpressed myostatin on myoblast proliferation, differentiation, and apoptosis is extended to endogenous myostatin.

Though some differences in overexpression or inhibition of endogenous myostatin were observed, it appears that myogenin and p21 are essential targets of this growth factor.
Revue / Journal Title

Experimental cell research ISSN 0014-4827 CODEN ECREAL
Source / Source

2003, vol. 286, no2, pp. 263-275 [13 page(s) (article)]
Langue / Language

Anglais

Editeur / Publisher

Elsevier, Orlando, FL, ETATS-UNIS (1950) (Revue)

Localisation / Location

INIST-CNRS, Cote INIST : 5763, 35400011822419.0100

What the hell do they mean by over-expressed but not endogenous?

If it is expressed in the cell doesn't it have to be considered endogenous?

I am going to have to read this again tomorrow, as this is seeming counter-intuitive to what I would have thought they were implying about myostatin, that is is going to be like p53 but for muscle, that is protecting against unregulated/cancerous cell growth.

Dr Pangloss
05-12-2009, 08:15 PM
hey HeavyIron, this is the paper...

mopain4u
05-20-2009, 01:18 PM
WOW!!! i thought i was at least semi-intelligent until i read this thread. do you think you could do some of us lesser edumacated a favor and maybe break this down into simpler terms. i'm slow and from the south so i'd really appreciate it.:bowdown:

Dr Pangloss
05-20-2009, 06:06 PM
WOW!!! i thought i was at least semi-intelligent until i read this thread. do you think you could do some of us lesser edumacated a favor and maybe break this down into simpler terms. i'm slow and from the south so i'd really appreciate it.:bowdown:

simply put, there is a protein your body makes called 'myostatin' and it limits muscle growth.

the use of steroids appears to elevate this stuff after 8-10 weeks. This coincides with the time-frame in which steroids have diminished effect in a cycle.

It suggests that perhaps one should limit cycles to 8-10 weeks.

mopain4u
05-21-2009, 02:38 AM
oooohhhhhh... makes perfect sense now. thanks :beerbang:

DocGabri
05-21-2009, 03:42 AM
Another interesting read DocP

heavyiron
05-21-2009, 12:11 PM
hey HeavyIron, this is the paper...
Very interesting stuff man.
Thank you!

fury-
05-22-2009, 08:53 PM
what about michael lockett? or the kids that were recently found with myostatin mutations... one in the states supposedly doesnt have the receptor for myostatin, while a kid in germany doenst produce myostatin at all... give them test all their life lol

heavyiron
06-09-2009, 12:17 PM
Dr P
I had a chance to look at the complete study and apparently by week 20 myostatin levels returned to baseline meaning that staying on may be another strategy.




4. Discussion
Previous data on circulatingmyostatin levels in healthy individuals
and in individuals with disease are confounded by issues of
specificity and the inability of these earlier assays to reliably take
into account the binding of circulatingmyostatin to its binding proteins
in plasma. In our assay,myostatin was stripped off its binding
proteins by acid treatment that effectively dissociates myostatin
from the binding proteins. Other serum proteins do not have significant
cross-reactivity in our assays; even the highly homologous
GDF-11 protein is not expected to cross-react in the assay because
the RK-22 detector antibody in the sandwich ELISA does not bind
to GDF-11. The assay has all the characteristics of a valid measurement
system: nearly 100% recovery of spiked myostatin, excellent
precision in the physiologic range, and accuracy. The assay also has
sufficient sensitivity to be able to measure circulating myostatin
concentrations in almost all men and women.
Using this validated myostatin assay, we report here the distribution
of myostatin levels in healthy men and women. Although
direct comparisons with previous assays are difficult because of
the differences in calibrating standard, we find that the circulating
concentrations in men and women are substantially lower
than those reported previously.We show that myostatin levels are
lower in older men than young men. Also, contrary to expectation,
myostatin levels increased transiently in response to testosterone

administration, but returned to baseline by 20 weeks of treatment.
The increments in myostatin levels were correlated with
circulating testosterone concentrations. These observations support

the hypothesis initially proposed by

Lee (2004) and later by

Gaussin and Depre (2005)


that myostatin acts as a chalone – a

counter-regulatory hormone – to restrain skeletal muscle growth
in response to an anabolic stimulus.
The concept of chalones – inhibitors of cell growth that serve as
counter-regulatory mechanisms to control the size of specific tissues
– was introduced initially by Bullough. However,


Lee (2004)

was the first to articulate the hypothesis that myostatin functions
as a chalone for skeletal muscle: it is produced and secreted by
skeletalmuscle and it circulates in plasma to restrain skeletalmuscle
mass. Our data support Lee’s prescient prediction; myostatin
levels are increased in response to the increase in skeletal muscle
mass induced by testosterone administration. The increments in
myostatin levelswere correlated with testosterone concentrations.
Thus, testosterone administration increases muscle mass resulting
in increasedmyostatin production and secretion; it is possible that
the increased circulatingmyostatin levels in turn restrain unlimited
growth of skeletal muscle in response to continued testosterone
administration. Similarly, older men with lower skeletal muscle
mass have lowermyostatin levels than young men; one could speculate
that aging is associated with loss of skeletal muscle mass,
leading to decreasedmyostatin secretion, which in turn brakes further
muscle loss. In separate studies,


Shyu et al. (2005) reported that

cyclic mechanical stretch upregulates IGF-1 as well as myostatin
expression. The stretch-induced myostatin increase in cardiomyocytes
is mediated by IGF-1 in part through MAP kinase and MEF2
pathway. In an accompanying editorial,


Gaussin and Depre (2005)

suggested thatmyostatin represents a chalone of IGF-1 pathway in
the heart. IGF-1 induces cardiac muscle hypertrophy resulting in
increasedmyostatin production that then checks further hypertrophy
of the cardiac muscle.
The availability of a reliable assay for accurate measurement
of myostatin levels provides an excellent opportunity to examine
the physiologic regulation of circulatingmyostatin levels in healthy
humans and in patients with clinical disorders associated with loss
of skeletalmuscle mass. In this study, under basal steady-state conditions,
serummyostatin levelswere not correlated with lean body
mass; thus,myostatin levelsmaynot be a good biomarker of skeletal
muscle mass.However, observations thatmyostatin levels rise early
during the course of testosterone-induced muscle mass accretion
raise the possibility that myostatin levels might serve as a useful
early biomarker for the anabolic effects of promyogenic therapies
such as testosterone. This speculation needs further investigation.

Dr Pangloss
06-09-2009, 06:03 PM
great eye. i looked at the full-length but didn't see that. there is no doubt that higher myostatin levels would inhibit growth though.

It appears to be triggered by changes in Test levels, so i wonder if a low dose for a very long time doesnt make the most sense.

like 350-450 mg for 26 weeks or greater.

heavyiron
06-09-2009, 06:47 PM
great eye. i looked at the full-length but didn't see that. there is no doubt that higher myostatin levels would inhibit growth though.

It appears to be triggered by changes in Test levels, so i wonder if a low dose for a very long time doesnt make the most sense.

like 350-450 mg for 26 weeks or greater.
I have always been skeptical of the pros who said they were only on 600mg of test per week but this makes more sense if they are doing 6 month plus cycles now. It is interesting but still preliminary.

Dr Pangloss
06-09-2009, 06:57 PM
I have always been skeptical of the pros who said they were only on 600mg of test per week but this makes more sense if they are doing 6 month plus cycles now. It is interesting but still preliminary.

It's always a partial information game. one can make it more accurate by sticking to literature and leaving brologic behind, however....:p

heavyiron
06-09-2009, 07:13 PM
I am totally with you brother!

Tatyana
06-09-2009, 07:16 PM
great eye. i looked at the full-length but didn't see that. there is no doubt that higher myostatin levels would inhibit growth though.

It appears to be triggered by changes in Test levels, so i wonder if a low dose for a very long time doesnt make the most sense.

like 350-450 mg for 26 weeks or greater.

So obviously, women are going to have lower myostatin levels, which is why some can put on a significant amount of muscle without high testosterone levels.

I heard this several years ago and I wonder if there is any truth to this:

Nitric Oxide induces follistatin which inhibitis myostatin.

Dr Pangloss
06-09-2009, 07:21 PM
follistatin does inhibit myostatin, but it binds lots of other tgf beta family members, which are all involved with growth and differentiation. I'm a little reluctant to even suggest trying follistatin at this point.

i'd prefer a more specific inhibition.

it should be noted that elevated follistatin does result in increased muscle, which suggests the effects on the other tgf beta members might not be so critical.

JohnBoy
06-10-2009, 10:47 AM
These may be a few amateur questions, but would a different testosterone have a different effect on myostatin levels (ex: cypionate, enanthate, etc...)? And can we conclude that myostatin regulates muscle growth while testosterone promotes it? So, myostatin acts as, at least temporarily, as a stopper for hypertrophy or does it actually go so far as to catabolize muscle in increased amounts?

Tatyana
06-12-2009, 01:06 PM
These may be a few amateur questions, but would a different testosterone have a different effect on myostatin levels (ex: cypionate, enanthate, etc...)? And can we conclude that myostatin regulates muscle growth while testosterone promotes it? So, myostatin acts as, at least temporarily, as a stopper for hypertrophy or does it actually go so far as to catabolize muscle in increased amounts?




The esters on anabolic steroids have more to do with how long they last in the body. Most hormones have a very short half-life, attaching these chains alters that dynamics.

Once these various forms of tesosterone hit the receptors, test is test, and it will initiate the same cellular response.



We have all sorts of controls in our body so that cells do not grow in an unregulated manner, which can be defined as cancer. Myostatin is this control mechanism for muscle cells, it is a growth inhibitor, as far as I am aware, it isn't going to catabolise muscle.

As with all things in physiology/biochemistry, it is never a good/bad - on/off situation, it is always a fine balance.

I just had to mention that as it would be silly for people to start to designate myostatin as BAD, it does serve a purpose, and our understanding of things like cell growth and differentiation is still really incomplete.

Klaus Urine
06-12-2009, 05:51 PM
The esters on anabolic steroids have more to do with how long they last in the body.That's exactly what they do.

Dr Pangloss
06-12-2009, 06:11 PM
there is one paper that indicates myostatin does not function by inhibitiing muscle cell or satilite cell proliferation, which is certainly a counter-intuitive finding.

Tatyana
06-12-2009, 06:17 PM
That's exactly what they do.

Cool, I just don't know which ones are longer or shorter and the length of time they last.

Cliff notes?

hilly
06-13-2009, 04:04 AM
simply put, there is a protein your body makes called 'myostatin' and it limits muscle growth.

the use of steroids appears to elevate this stuff after 8-10 weeks. This coincides with the time-frame in which steroids have diminished effect in a cycle.

It suggests that perhaps one should limit cycles to 8-10 weeks.


so in theory would this mean that the idea of blast and cruising for longer periods of time is detrimental? or would the cruise period of 100-300mg test only be enough to lower myostatin?

maxititer
06-13-2009, 04:48 AM
myostatin can be regulated by siRNA, it was already done (from private conversation)

fraction of fetal liver cells were transformed with adeno vector producing anti myostatin siRNA. Single injetion lasted for 6 months. Also by injecting more or less cells effect can be rugulated. That can be arranged, PM me when you are ready to spend 30K.

esplendido
06-13-2009, 11:30 PM
I wonder if the percent in rise of myostatin is in direct relationship to the rise in muscle mass, i.e. you have an increase of 15% in muscle mass, do you have a cooresponding 15% rise in myostatin?

If that's the case, the growth hindering factor of myostatin is no greater in hypertrophied muscle than it is in the muscle prior to hypertrophy....which might be why increasing the dose of testosterone over the period of administration nets more lean muscle mass.

I've continued strength and size increases over 20 weeks by gradually increasing the dose of test, usually by 1/2 gram after 10 weeks, and another 1/4 gram after 15 weeks.

Or, perhaps myostatin increases in reaction to increased test is slower than the effects of the test in the early dosing.

I do think that some pros are using doses considered small in pro bbing circles because they're not looking for increased size after awhile. They have all the size they need and just want to hold onto it as they prepare for shows.

maxititer
06-14-2009, 12:36 AM
there is a lot of controversies regarding myostatin in scientific literature. I think it will continue for more 10 years at least.

From practical point view important to consider what is interaction between IGF1 and myostatin. IGF1 is main regulator of growth and myostatin main inhibitor of growth. IGF1 is presented at any monent in large amounts, so naturally myostatin have to presented in quite large amounts too.

On one side, because myostatin acting by disrupting cycline D pathway, once this pathway disrupted the cells cant divide. But once cyclin D pathway activated by IGF1, myostatin cant affect these cells. IGF1 attenuate action of myostatin. For example rise in basal IGF1 after gh injection, will result in rise of myostatin too, but myostatin cannot affect IGF1 activated cells and those cells will continue dividing.

On another side the cross talk between IGF and myostatin signaling pathways may result in growth and in growth suppression as well, depending upon the context.

That kind of speculations did not going to bring any clarity on that question for very long time as amount of data involved in IGF1 and myostatin signaling pathways are huge.

My current idea is that when AAS and GH used same time myostatin did not play significant role. Because even despite of rise in myostatin level IGF1 still works.

NPCKnight
07-03-2009, 03:16 AM
So instead of people 'frontloading' things like testosterone for 1-3 weeks, wouldn't it make sense to run that 'big, frontloaded' dose for 8-10 weeks, and if you stayed on...drop it down to 500mg or so after?

saiyajinali
07-10-2009, 02:10 PM
How long after on ceases the use of testosterone before the myostatin levels decrease I wonder? The reason I ask is it possible if one were to swap over to a more anabolic low androgen compound like Var or Winny, while the myostain levels restore to normal levels, & then you could reintroduce the testosterone to get the full benefits again?

indianamonster1986
07-10-2009, 02:43 PM
Good stuff doc!!!

Dr Pangloss
07-10-2009, 02:48 PM
So instead of people 'frontloading' things like testosterone for 1-3 weeks, wouldn't it make sense to run that 'big, frontloaded' dose for 8-10 weeks, and if you stayed on...drop it down to 500mg or so after?


I'm trying a similar protocol now. it's basically a cruise after 8 weeks. I'm week two of a 4 week cruise, then back up for 8 weeks.

the other is to just stay on, because apparently the levels go back down eventually.

Dr Pangloss
07-10-2009, 02:49 PM
How long after on ceases the use of testosterone before the myostatin levels decrease I wonder? The reason I ask is it possible if one were to swap over to a more anabolic low androgen compound like Var or Winny, while the myostain levels restore to normal levels, & then you could reintroduce the testosterone to get the full benefits again?


i dont know exactly on any of your points. More research is needed.

heavyiron
07-11-2009, 11:19 AM
How long after on ceases the use of testosterone before the myostatin levels decrease I wonder? The reason I ask is it possible if one were to swap over to a more anabolic low androgen compound like Var or Winny, while the myostain levels restore to normal levels, & then you could reintroduce the testosterone to get the full benefits again?
I think for the pro bodybuilder staying on test makes the most sense. Remember that myostatin returns to normal (baseline) even while on after 20 weeks. Aas users typically increase dose at weeks 7-9 to avoid plateaus. The plateaus must be due in some part to myostatin levels although there must be other factors. We essentially use higher and higher doses or more anabolic drugs to push gains. This is where mega dosing becomes popular. But we need to think in terms of safety to our health so the alternative is moderate doses of test for years. If you use 600mg per week of test you will likely hit a plateau after 8-9 weeks but if you keep using through 20 weeks gains should resume because at least 1 growth limiting factor has returned to baseline (myostatin). When I first saw this data I thought I would just cruise with low doses from weeks 9-20 (kinda like your idea) but the more I talk to competitors who have been on for years the more I kept hearing the same answer. Moderate doses for years is what works. Now 600mg per week can have some negative effects to lipids so obviously we need to address that through diet and support sups. but compared to massive cycles that push gains, 600mg weekly has to be less stressful.
If you had a show and wanted to add a strong anabolic the weeks leading up to it then tren seems to be the answer. Basically you would do one massive cycle per year leading up to the show and cruise on moderate test the rest of the year.
I have talked to my doc about PCT and he has told me that cruising is less stressful to the body than going on and off. Of course he is talking in terms of much lower doses but I think with regular blood work and addressing estro sides one could cruise at 600mg per week with minimal stress. I am only talking about competitors here and not gym rats in case any of them are thinking of doing this. Anyway, this is pretty interesting stuff and my hope is that we see more data on this topic soon.

Dr Pangloss
07-11-2009, 12:16 PM
I think for the pro bodybuilder staying on test makes the most sense. Remember that myostatin returns to normal (baseline) even while on after 20 weeks. Aas users typically increase dose at weeks 7-9 to avoid plateaus. The plateaus must be due in some part to myostatin levels although there must be other factors. We essentially use higher and higher doses or more anabolic drugs to push gains. This is where mega dosing becomes popular. But we need to think in terms of safety to our health so the alternative is moderate doses of test for years. If you use 600mg per week of test you will likely hit a plateau after 8-9 weeks but if you keep using through 20 weeks gains should resume because at least 1 growth limiting factor has returned to baseline (myostatin). When I first saw this data I thought I would just cruise with low doses from weeks 9-20 (kinda like your idea) but the more I talk to competitors who have been on for years the more I kept hearing the same answer. Moderate doses for years is what works. Now 600mg per week can have some negative effects to lipids so obviously we need to address that through diet and support sups. but compared to massive cycles that push gains, 600mg weekly has to be less stressful.
If you had a show and wanted to add a strong anabolic the weeks leading up to it then tren seems to be the answer. Basically you would do one massive cycle per year leading up to the show and cruise on moderate test the rest of the year.
I have talked to my doc about PCT and he has told me that cruising is less stressful to the body than going on and off. Of course he is talking in terms of much lower doses but I think with regular blood work and addressing estro sides one could cruise at 600mg per week with minimal stress. I am only talking about competitors here and not gym rats in case any of them are thinking of doing this. Anyway, this is pretty interesting stuff and my hope is that we see more data on this topic soon.


there may indeed be other limiting factors, but as you said there is no doubt myostatin is contributing to inhibiting gains, as that is its prime function.

i agree that long-term moderate doses are probably the best.

thewhite9t
08-06-2009, 12:17 PM
I joined to bump this thread because it is extremely interesting.

Any more thoughts?

Dr Pangloss
08-06-2009, 06:11 PM
we're waiting for more data.

jbruno7272
08-06-2009, 07:09 PM
Dr. Pangloss, My current cycle I started with 250 ml of Test E eod for 1st 8 weeks and switched to 300 Sustanon eod for the final 8 weeks as suggested by Dave. I noticed about week 10 gains slowed considerably. In the future should I limit myself to 10 week cycles(what I am reading here has made me consider than staying on 16 weeks may be pointless)? Also, I am hesitant to cruise between cycles as I fear that I will need to be on HRT the rest of my life but when you cruise what sort of dosages are you talking about? When you aren't cruising as well.

Dr Pangloss
08-06-2009, 07:18 PM
for someone who is not willing to cruise or use continuously, 8-10 week cycles make the most sense.

The time off in between is at your discretion.

B7emm
08-06-2009, 07:23 PM
DR. P,

How long do you feel it takes for the receptors to return to optimal levels? for instance i respond better with 6weeks off than with 3.

Dr Pangloss
08-06-2009, 07:25 PM
DR. P,

How long do you feel it takes for the receptors to return to optimal levels? for instance i respond better with 6weeks off than with 3.


it's not receptor desensitization brother. that's a myth. the point of this whole thread is that rises in myostatin levels at 10 weeks contribute to slowing gains.

6 weeks sounds good.

B7emm
08-06-2009, 10:35 PM
thanks bro. good to know.