Receptor downregulation question for guys that stay on year round

**Polska** · 05-21-2009, 10:52 PM

For you guys that stay on all year with blast/cruise phases, how do you deal with androgen receptor down regulation? After staying on for "x" amount of time would you not just get diminished returns for all your efforts? Or does cruising in phases allow the receptors to up regulate while still technically being "on"?

**Merc.** · 05-21-2009, 11:02 PM

Talking about androgen receptors it's fairly safe to say that they dont down regulate...

In fact they actually increase in the presence of more androgen's ..

You see what actually shuts down - your growth - is the build up of other reaction factors ( such as cortisol, glycogen as well as SHBG ) that the body pumps out to bring you back into hematosis...

Merc.

**SilverTest** · 05-21-2009, 11:04 PM

bro there is no such thing as receptor downregulation its not real , receptors die off and are created again in the body about every 30 days.

you wont keep blowing up , but you will keep adding quality muscle to your frame and you will see it with time that your whole body makeup will change as time goes on.

**SilverTest** · 05-21-2009, 11:05 PM

Originally Posted by Merc.

Talking about androgen receptors it's fairly safe to say that they dont down regulate...

In fact they actually increase in the presence of more androgen's ..

You see what actually shuts down - your growth - is the build up of other reaction factors ( such as cortisol, glycogen as well as SHBG ) that the body pumps out to bring you back into hematosis...

Merc.

yes in addition to what merc said above they actually increase in the presence of more androgens.

**Polska** · 05-21-2009, 11:07 PM

Originally Posted by Merc.

Talking about androgen receptors it's fairly safe to say that they dont down regulate...

In fact they actually increase in the presence of more androgen's ..

You see what actually shuts down - your growth - is the build up of other reaction factors ( such as cortisol, glycogen as well as SHBG ) that the body pumps out to bring you back into hematosis...

Merc.

Originally Posted by SilverTest

bro there is no such thing as receptor downregulation its not real , receptors die off and are created again in the body about every 30 days.

you wont keep blowing up , but you will keep adding quality muscle to your frame and you will see it with time that your whole body makeup will change as time goes on.

So the theory about your first cycle being your best and to make the most of it because of 'virgin receptors' is a myth?

**Polska** · 05-21-2009, 11:09 PM

Originally Posted by Merc.

You see what actually shuts down - your growth - is the build up of other reaction factors ( such as cortisol, glycogen as well as SHBG ) that the body pumps out to bring you back into hematosis...

So then how do you avoid these factors while on year round? Are cruising/blasting and load/deload phases enough to keep the body guessing and the key to continued gains while on all the time?

**SilverTest** · 05-21-2009, 11:12 PM

Originally Posted by Polska

So the theory about your first cycle being your best and to make the most of it because of 'virgin receptors' is a myth?

yes IMO. People always make great gains on cycle , well..hum..most of the time.

first cycles are like that because its a new kind of feeling and you kind of get really big and stuff , it takes you to a whole new level, thats why it feels like its the best cycle.

just like humpin think about it lol , the first drills are the best right ???

lol.

**SilverTest** · 05-21-2009, 11:13 PM

Originally Posted by Polska

So then how do you avoid these factors while on year round? Are cruising/blasting and load/deload phases enough to keep the body guessing and the key to continued gains while on all the time?

yes that is correct.

**MuscleScience** · 05-21-2009, 11:36 PM

I replied in a very similar thread about this subject to and extent.
"muscle memory" and gear

Originally Posted by Iceman69

Please explain bro.

Because my personal experience has been that after several cycles of AAS my natural "baseline" has been raised.

Iceman

Well my mind was working and I came to a conclusion from several things. I knew several things one being that when a muscle cell is under stress such as when its being continuously trained the infusion of satellite cells increases. Satellite cell metaplasia adds to the nuclear count of muscle cells. Because muscle cells themselves can not divide because they are so specialized that the mechanisms for cell replication are completely unexpressed. Now if you have an infusion of new nuclei from satellite cells which are basically stem cells that are not nearly as specialized as a muscle cell is. They can express such things as more Androgen receptors and can add to protein synthesis. The nucleus donated by the satellite cells stays on the outer borders of the muscle cell that it infused with. The satellite cells nucleus does not seem to completely mature to act like a native muscle nucleus. It basically acts like a support cell much like glial cells in the nervous system.

My conclusion is that AAS dramatically increases satellite cell metaplasia even over trained individuals that train naturally. This increase in permanent or at least is very long lasting. I think or at least one theory is that having this permanent change in the muscles nuclear count is what causes the increase in baseline muscle mass if you will. Keep in mind this is my own conclusion and I have not seen to date anything in the literature that says this is a definite possibility. Everything else not in bold is currently what the literature shows at present.

**powerliftmike** · 05-21-2009, 11:56 PM

Originally Posted by Merc.

Talking about androgen receptors it's fairly safe to say that they dont down regulate...

In fact they actually increase in the presence of more androgen's ..

You see what actually shuts down - your growth - is the build up of other reaction factors ( such as cortisol, glycogen as well as SHBG ) that the body pumps out to bring you back into hematosis...

Merc.

Correct, except for the part about hematosis, whatever that is..its homeostasis

**jimmyinkedup** · 05-22-2009, 07:03 AM

I get flack for my opinions on this ..but i tend to disagree somewhat.
1- In no way am i convinced receptor #'s can increase fast enough to maintain gains
2- Makes little sense that the body would also not dispose of excess cortisol etc as it would other hormones preventing levels from increasing to the point where gains cease
3- shbg could be controlled with ancillary compounds - yet gains still diminish / cease
Not to be difficult here but i am far from convinced that downreg doesnt exist. Im familiar with bodies disposal methods of excess hormones etc ...but im not sold on this theory.
Merc if you wanted input on an article ..id love to see a non biased write up on this...im not the be all end all by any means BUT i have a little knowledge and im not so sure on this one. JMO.....

**tMQ** · 05-25-2009, 02:18 AM

More muscle = more receptors = more shbg
Slin + proviron lowers shbg
So... Every 12 weeks hcg + clen + slin + proviron for 2 weeks may help I guess

**Swifto** · 05-25-2009, 07:59 AM

Originally Posted by Merc.

Talking about androgen receptors it's fairly safe to say that they dont down regulate...

In fact they actually increase in the presence of more androgen's ..

You see what actually shuts down - your growth - is the build up of other reaction factors ( such as cortisol, glycogen as well as SHBG ) that the body pumps out to bring you back into hematosis...

Merc.

Originally Posted by MuscleScience

I replied in a very similar thread about this subject to and extent.
"muscle memory" and gear

Well my mind was working and I came to a conclusion from several things. I knew several things one being that when a muscle cell is under stress such as when its being continuously trained the infusion of satellite cells increases. Satellite cell metaplasia adds to the nuclear count of muscle cells. Because muscle cells themselves can not divide because they are so specialized that the mechanisms for cell replication are completely unexpressed. Now if you have an infusion of new nuclei from satellite cells which are basically stem cells that are not nearly as specialized as a muscle cell is. They can express such things as more Androgen receptors and can add to protein synthesis. The nucleus donated by the satellite cells stays on the outer borders of the muscle cell that it infused with. The satellite cells nucleus does not seem to completely mature to act like a native muscle nucleus. It basically acts like a support cell much like glial cells in the nervous system.

My conclusion is that AAS dramatically increases satellite cell metaplasia even over trained individuals that train naturally. This increase in permanent or at least is very long lasting. I think or at least one theory is that having this permanent change in the muscles nuclear count is what causes the increase in baseline muscle mass if you will. Keep in mind this is my own conclusion and I have not seen to date anything in the literature that says this is a definite possibility. Everything else not in bold is currently what the literature shows at present.

Mysostatin levels also play a crucial role. This could explain why gains diminish after 8-10 weeks.

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

Lakshman KM, Bhasin S, Corcoran C, Collins-Racie LA, Tchistiakova L, Forlow SB, St Ledger K, Burczynski ME, Dorner AJ, Lavallie ER.
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]

**MuscleScience** · 05-25-2009, 10:47 AM

Originally Posted by Swifto

Mysostatin levels also play a crucial role. This could explain why gains diminish after 8-10 weeks.

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

Lakshman KM, Bhasin S, Corcoran C, Collins-Racie LA, Tchistiakova L, Forlow SB, St Ledger K, Burczynski ME, Dorner AJ, Lavallie ER.
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]

Good Call Swifto!

**Swifto** · 05-25-2009, 11:35 AM

Originally Posted by MuscleScience

Good Call Swifto!

Thought you'de like that my friend.

**jimmyinkedup** · 05-25-2009, 02:00 PM

^^^ good post and definitely intriguing....far from definitive but hopefully more to come on that theory. Thanks Swifto....

**Immortal Soldier** · 05-25-2009, 10:44 PM

If myostatin is the culprit behind deminishing gains it makes sense. It's the human evolutionary gene that restricts muscle growth, when the body (on cycle) starts growing to fast it is possible the bodys natural response would be to increase myostatin levels thus baselining gains. The body is shocked that its growing so much muscle and it goes against evolutinary surivial principles because the person now requires more and more food and calories to maintain the body and it is slower and more bulkier which goes against the natural "lean" frame of the human body.

This would be my guess to Swifto's comment about myostatin, I am no scientist so you guys probably no better than I do on this.