Importance of Offtimes and The Receptor Downregulation Myth

[Krzna]

So what is the point of this thread?
Time in an out we see the question popping up about cycles, recovery and doing more cycles. If you are new to hormones and you have tried some hormonal alternativ, sure you will like it. Its a hormone, you will grow, period! Unless you're diet is pathetic and your training is worse, you will have gains.

And you are saying back to back cycles are wrong?
It is normal that people get addicted to this growth phase. Like the saying, power corrupts, absolute power corrupts absolutely, people are greedy for more mass, more results. I dont blame you, I was like this too. However, if one understand the science behind this we will make better more intelligent decesions regarding cycles within a certain time line.

So your point is?
To be on the safe side, I would never advise more than two properly planned prohormonal cycles within one calendar year. There are different ways to keep the body anabolic even after a cycle and my next write up will have more on that.

So on doing PCT, getting estrogen out, everything is solved rite?
Elevated hormone levels, in general, will cause inhibition of natural testosterone production. Many ph users have a misconception that elevated estrogen levels alone are the sole cause of inhibition, think that by blocking estrogen, they can block inhibition. This is totally flawed reasoning and there is much more to inhibition than just estrogen.

Progesterone is another hormone that can cause inhibition, when used long-term. Paradoxically, in the short term it can be stimulatory. However as cycle length increases its effect are detrimental.
Other relevant factors include beta agonists, opiates, melatonin, prolactin, and probably other compounds. With the exception of beta agonists (e.g. ephedrine and Clenbuterol) and opiates (natural endorphins on the one hand being inhibitory, and Nubain blocking such inhibition).


Off periods are based upon the effects the protocol had upon the Hypothalamus-Pituitary-Testes-Axis (HPTA). In the case that one records heavy aromatization and such phs are used there is a negative feed-back loop that signals testes shut-down for natural androgen production.
If effective dosages of anti-aromatase and anti-progestin drugs are employed during a protocol, the shut-down of testicular function is less severe.

Assuming the user has a correctly structured ON cycle protocol and if he has used proper estrogen/progestin control, and done post-cycle therapy, most will maintain 35-50% normal HPTA function with a 6-10 week off period from AAS.

The idea of bridging - running back to back cycles often leads to negative concerns such as significant elevation of hemocrit and HDL/LDL ratio issues quite needlessly. Sometimes people do not keep their gains after the ph cycle and get paranoid about the loss in size. The misconception that getting back ON a cycle will give back all the lost size is very damaging to the body.

Additionally the cellular proteins responsible for the anabolism realized from AAS use can reach a state of decreased activity (burnout) and little or no results occur during following cycles. I am not going to deal with receptor downgrading here as this is a topic of discussion.

While ON a ph cycle a person experiences a decrease in activity from cortisol release. Cortisol is an adrenal hormone that is quite catabolic to muscle tissue (it eats it up as an energy source). All AAS have some level of anti-cortisol value in that they merge with and block cortisol receptors.

During off periods cutting 20-30% of volume is a must for the first few weeks post protocol while HPTA function begins to recover and natural androgen production improves.


Regulation of receptors - The concepts

"Regulation" of a receptor refers to control over the number of receptors per cell. "Sensitivity" in contrast, refers to the degree of activity each receptor has. It is a possible in many cases for the receptors of a cell to be sensitized or desensitized to a drug or hormone, independently of the number of receptors. Similarly, it is possible for the receptors to upregulate or downregulate, to increase or decrease in number, independently of any changes in sensitivity. Eg Keitofen/ Benadryl for Clen/Ephidrine.

Proposed arguments for disproving the hypthesis that AR downregulation exists.

There is no scientific evidence whatsoever that AR downregulation occurs in human muscle, or in any tissue, in response to above normal (supraphysiological) levels of AAS.

• AR downregulation has been seen in cell culuture in labs, however, one cannot genralize as the body of the hormone/ph/AAS user recieves different stimulii from different sources levels etc.

•Down regulation of receptors in cellular level does not support the pattern of growth with respect to AAS/ph use in users however upregulation does support this pattern.

• The "theoretical" arguments advanced by proponents of AR downregulation are invariably without merit.


These points included, one can say that receptor clogging, dirty receptor concept etc are misconceptions. However, different people have different views on the matter. I hope this thread will lead to an intelligent discussion in this regard.


I would like to give full credit to ALR,William Llewellyn and Karl "Nandi" Hoffman for their educational writeups that has helped so many understand androgen activity at cellular level.

[<^>]

damn fine read bro !

[BillyB]

Damn Krzna,

You are on fire! Kick ass posting!

[gymownr]

good post krzna u da man
got a question for u.
would it be safe to run short 3 2week cycles in 1 year using sd or ergo.
am asking this cause i did sd for 3weeks and got the most gains and no noticable sides for 2weeks. the last week i.e. week 3 say sides like bp, shrinkage, shutdown and total labido loss.
so would it be safe to run 2week cycles 3times a year with proper pct of 2-3weeks doing then 3-4mts apart.

[ScrillaKeith]

Another great post man! Keep em coming!

[Krzna]

Ok guys, take a look at this.

http://www.ncbi.nlm.nih.gov/entrez/q..._uids=11300231


Just as a jist of the entire piece, the research by Sulcova et al showed 7.4 % drop (of borderline statisticaly significance according to the authors) drop in cortisol after transdermal 7-keto DHEA application

Also one can argue how effective these are at blocking cortisol; combined with phosphytidyl serine one might see a larger drop in cortisol.

Clearly from the perspective of AR downregulation, cortisol is not a good thing. But one should also bear in mind that it acts acutely as a lipolytic hormone.

One of the reasons why 7oxo DHEA is an awesome part of any bridge/PCT and gets your body back to a totally natural anabolic state.

[Krzna]

More over

http://jcem.endojournals.org/cgi/content/full/86/5/2296


Muscles contain 11 beta-HSD type I, which converts inactive cortisone to cortisol. I am trying to figure out the relationship between IGF supplementation and the presence of inhibiting cortisol conversion.

That understood, IGF should be an effective part of PCT, helping no only in keeping gains but also leaning out/ reducing muscle bloat.

[ripped edges]

Originally Posted by Krzna

More over

http://jcem.endojournals.org/cgi/content/full/86/5/2296


Muscles contain 11 beta-HSD type I, which converts inactive cortisone to cortisol. I am trying to figure out the relationship between IGF supplementation and the presence of inhibiting cortisol conversion.

That understood, IGF should be an effective part of PCT, helping no only in keeping gains but also leaning out/ reducing muscle bloat.

Damn Mr.scientist very impressive and interesting. Will be watching.

[ScrillaKeith]

bump

[Borden_john]

great post