Oral Cycle plan - Binding affinity is the question

[Mister_T_]

Been planning this cycle for months now and have everything on deck... including proper SERM (nolvadex & Exemestane)

My Question is in terms of binding affinity. Will the plan I have be plenty effective or should I remove a compound?

Tren (19-norandrosta-4-9,diene-3,17-dione) 2 caps-50mg AM/50mg PM
LGD- 4033 4-8mg pm dose
Epi andro 500-750mg daily

Support Supps
Ashwaghanda
Follidrone 2.0
Tudca

PCT
K1ngs Blood
Trib A
Inhibit P
Nolvadex


My plan is to start the epi andro 2 weeks before the Tren/LGD so that is in working mode and my physique starts to harden up.

After some recent research I am concerned that the Tren and LGD will compete for receptors and in turn decrease potential gains.

Please feel free to share thoughts, thank you.

 

[NewAgeMayan]

I think youll be fine bro. Receptor "absolute saturation" is highly unlikely in this and any practical scenario. Even if it were practically possible to totally saturate receptors, youd have no way of knowing what amounts would be required to do so yourself.

Guys run compounds at doses far greater than what youre planning. Compounds are not like sperm fighting to get to that one egg; if there are receptors available, the compound will potentially activate them.

 

[Mister_T_]

Okay right on, sounds like I was overthinking the situation. Thank you sir

 

[NewAgeMayan]

Researchers hypothesize that one reason natural hormones like testosterone are "pulsed" by the body is due to androgen receptor sensitivity also varying over a typical 24hr period.

If this scenario, or something like it, is accurate, then the idea of AR saturation becomes much more complex.

 

[2kvette]

What happens with the so called Receptor desensitization is this. Just like the HPTA is subject to negative feed back, the receptors themselves are too. As more AR's get activated regulatory proteins inactivate the receptors or degrade them. Also, repressor proteins stop the gene expression that androgen receptor activation induces. In total, there are actually three feedback loops that control this part of physiology. One is controlled through negative feedback(hpta), the other two are controlled by allosteric feedback.

 

[NewAgeMayan]

How likely are we to max these systems out? Is it possible with the typical bber doses? Logic and anecdote says no...but science > logic.

 

[2kvette]

How likely are we to max these systems out? Is it possible with the typical bber doses?

Yea it is possible easily, but they just reset. This is why you get those big gains in the first few weeks of a cycle, and then they tapper off. It's because the receptors are literally disappearing!

 

[NewAgeMayan]

Yea it is possible easily, but they just reset. This is why you get those big gains in the first few weeks of a cycle, and then they tapper off. It's because the receptors are literally disappearing!

Ok. But I would think this phenomena would be more obvious/extreme the more compound(s) youre running, right? Like, the OP running tren/SARM/andro is not going to saturate his receptors to the same degree as the dude pinning 5ml oils per week?

 

[2kvette]

Ok. But I would think this phenomena would be more obvious/extreme the more compound(s) youre running, right? Like, the OP running tren/SARM/andro is not going to saturate his receptors to the same degree as the dude pinning 5ml oils per week?

Oh yea, definitely. Higher dose dose, more compounds, longer duration. These all equal more profound effect. So the milder the cycle, the less pronounced this is.

 

[NewAgeMayan]

Oh yea, definitely. Higher dose dose, more compounds, longer duration. These all equal more profound effect. So the milder the cycle, the less pronounced this is.

This sh1t is real interesting.

Why would those 3 AR regulatory systems have evolved? Like, what selection purpose would they serve? I cant think of any scenario in our evolutionary history where there would need to be regulations put on AR sensitivity. Our hormones are naturally pulsed, so its not like they are "omnipresent", but have peaks and troughs too

 

[muscleupcrohn]

This sh1t is real interesting.

Why would those 3 AR regulatory systems have evolved? Like, what selection purpose would they serve? I cant think of any scenario in our evolutionary history where there would need to be regulations put on AR sensitivity.

I remember in middle school biology, my teacher told us that any time we don't know the answer, just write "homeostasis."

 

[NewAgeMayan]

I remember in middle school biology, my teacher told us that any time we don't know the answer, just write "homeostasis."

Haha, yeah well that makes logical sense, but still has me wondering what could our ancestors have encountered that might have made 3 AR regulatory systems necessary/beneficial for improving Darwinian "fitness"?

 

[2kvette]

This sh1t is real interesting.

Why would those 3 AR regulatory systems have evolved? Like, what selection purpose would they serve? I cant think of any scenario in our evolutionary history where there would need to be regulations put on AR sensitivity. Our hormones are naturally pulsed, so its not like they are "omnipresent", but have peaks and troughs too

Androgens have roles other than building muscle and developing secondary sex characteristics. For example, prolonged high androgen levels can cause profound hypoglycemia. Not good for the species evolutionarily speaking. But these mechanisms aren't androgen specific, they are basically involved in every other ligand-cell signaling.

 

[NewAgeMayan]

Androgens have roles other than building muscle and developing secondary sex characteristics. For example, prolonged high androgen levels can cause profound hypoglycemia. Not good for the species evolutionarily speaking. But these mechanisms aren't androgen specific, they are basically involved in every other ligand-cell signaling.

Ah, yes, balance. Easy to forget there is more to the body than just gainz.

 

[2kvette]

Ah, yes, balance. Easy to forget there is more to the body than just gainz.

Lol, tell me about it

 

[NewAgeMayan]

Lol, tell me about it

Is there any one resource (book, publication or otherwise) that goes into all this AR function but isnt too heady for a layman

 

[2kvette]

Is there any one resource (book, publication or otherwise) that goes into all this AR function but isnt too heady for a layman

I don't know honestly. There might be. This was another aspect of my research I talked with you about last summer. Not steroids, not sarms, but a drug that increases androgen receptors. That way, even 10mg of test a week would elicit the gains of 400mg a week!

 

[NewAgeMayan]

I don't know honestly. There might be. This was another aspect of my research I talked with you about last summer. Not steroids, not sarms, but a drug that increases androgen receptors. That way, even 10mg of test a week would elicit the gains of 400mg a week!

Yeah what precisely would this entail? Like, a drug that causes AR proliferation? Or increases/prolongues sensitivity of whatever AR numbers you already have? Maybe Im visualising ARs wrong.

 

[muscleupcrohn]

I don't know honestly. There might be. This was another aspect of my research I talked with you about last summer. Not steroids, not sarms, but a drug that increases androgen receptors. That way, even 10mg of test a week would elicit the gains of 400mg a week!

I'm too tired to think straight (it's 3:26 AM), but I just read an interesting study on LCLT:

Twenty-one days of LCLT supplementation significantly (P G 0.05) increased pre- exercise vastus lateralis AR content compared with PL (Fig. 2). When RE was followed by water intake, AR content increased compared with PRE for PL only. Feeding following RE significantly increased AR content compared with pre-RE values for both LCLT and PL trials. In addition, for the LCLT trial, feeding significantly increased post-RE AR content compared with water intake.

Although studies in rats have shown that carnitine supplementation affects the hypothalamicYpituitaryYgonadal axis (4,19,20), no studies have investigated potential modifications in target tissue to accompany these central adaptations...

we hypothesize that the mechanism of LCLT action is enhanced T uptake via less muscle damage and increased availability of AR, and not due to direct stimulation of T secretion (i.e., LCLT is not a T-enhancing supplement)...

LCLT’s primary means of action, however, appears to be an up- regulation in AR content following 21 d of supplementa- tion. Finally, based on the results of the present study, LCLT and feeding may independently and synergistically enhance the hormonal environment following RE and promote recovery.

 

[2kvette]

Yeah what precisely would this entail? Like, a drug that causes AR proliferation? Or increases/prolongues sensitivity of whatever AR numbers you already have? Maybe Im visualising ARs wrong.

Exactly!!

 

[2kvette]

I'm too tired to think straight (it's 3:26 AM), but I just read an interesting study on LCLT:

Bingo!!! Now, to study the structure activity relationship in LCLT to see how it does it and improve it. TO THE LAB!

 

[NewAgeMayan]

I'm too tired to think straight (it's 3:26 AM), but I just read an interesting study on LCLT:

"...increased AR content."

What does this mean? I visualise an AR as a physical thing, that in the right conditions can be agonised/modulated/triggered/etc.

Increasing AR content to me sounds like youre making more of these things...wtf?

 

[muscleupcrohn]

Bingo!!! Now, to study the structure activity relationship in LCLT to see how it does it and improve it. TO THE LAB!

I'll meet you there. I need to go to the bed first.

 

[2kvette]

"...increased AR content."

What does this mean? I visualise an AR as a physical thing, that in the right conditions can be agonised/modulated/triggered/etc.

Increasing AR content to me sounds like youre making more of these things...wtf?

Right, say we have 5 AR normally per cell. Now, we give the body some substance to make each cell make 10 AR per cell.

 

[NewAgeMayan]

Right, say we have 5 AR normally per cell. Now, we give the body some substance to make each cell make 10 AR per cell.

Ah ok, so an AR is something that can be made quick smart? Lol, I just figured these things were grown (for want of a better term), and couldnt be cobbled together in a short space of time ie hours.

 

[2kvette]

Ah ok, so an AR is something that can be made quick smart? Lol, I just figured these things were grown (for want of a better term), and couldnt be cobbled together in a short space of time ie hours.

They body will make them need be. I wouldn't be surprised if you could double AR receptors in a matter of hours.

 

[muscleupcrohn]

Ah ok, so an AR is something that can be made quick smart? Lol, I just figured these things were grown (for want of a better term), and couldnt be cobbled together in a short space of time ie hours.

I haven't read though this, but it may be a good read:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2096617/

Also:

The purpose of this study was to investigate the immunohistochemical expression of androgen receptors (AR) in human vastus lateralis and trapezius muscles and to determine whether long-term strength training and self-administration of androgenic-anabolic steroids are accompanied by changes in AR content. Biopsy samples were taken from eight high-level power-lifters (P), nine high-level power-lifters who used anabolic steroids (PAS) and six untrained subjects (U)...

The proportion of AR-containing myonuclei per fibre cross-section was higher in the trapezius than in the vastus lateralis (P

Edit: Graphs

Edit 2: Perhaps giving some validity and/or explanation for saying "he's on steroids, look at his traps," haha.

 

[NewAgeMayan]

They body will make them need be. I wouldn't be surprised if you could double AR receptors in a matter of hours.

Well holy fuk.

Ok, bigger picture again. Say you come up with this compound that increases AR numbers significantly. Wont this have potential wider problems (problems that are typically avoided by regulatory systems)? Like, you mentioned hypoglycemia earlier as one possible outcome.

 

[2kvette]

Well holy fuk.

Ok, bigger picture again. Say you come up with this compound that increases AR numbers significantly. Wont this have potential wider problems (problems that are typically avoided by regulatory systems)? Like, you mentioned hypoglycemia earlier as one possible outcome.

This would be receptor specific, just targeting AR's

 

[2kvette]

I haven't read though this, but it may be a good read:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2096617/

Also:

The purpose of this study was to investigate the immunohistochemical expression of androgen receptors (AR) in human vastus lateralis and trapezius muscles and to determine whether long-term strength training and self-administration of androgenic-anabolic steroids are accompanied by changes in AR content. Biopsy samples were taken from eight high-level power-lifters (P), nine high-level power-lifters who used anabolic steroids (PAS) and six untrained subjects (U)...

The proportion of AR-containing myonuclei per fibre cross-section was higher in the trapezius than in the vastus lateralis (P

Edit: Graphs

Edit 2: Perhaps giving some validity and/or explanation for saying "he's on steroids, look at his traps," haha.

Yep, this study shows another good point. I'm glad you posted it. AR's decrease at a certain dosages, but then you hit this threshold where they skyrocket.

 

[muscleupcrohn]

To make things even more interesting (quoting examine.com because I'm too tired to type it myself):

In mammalian COS-7 cells, an ethanolic extract of the bark from Eucommia ulmoides is able to bind to and weakly activate the androgen receptor with enough affinity to displace testosterone with efficacy at a 5-25ng/mL range.[1] The addition of the extract to a medium containing DHT noted that even at saturating levels of DHT, Eucommia ulmoides augmented signalling in the range of 112-204% of baseline.[1] While this was found with the fractions containing triterpenoids, the caprylic acid content of Eucommia ulmoides and caprylic acid isolated from Coconut Oil both mimicked this augmentation.[1]

While oral intake of 1-50mg of the ethanolic extract in rats has failed to modify prostatic weights (suggesting weak androgenicity), it was able to increase the testosterone (5000mcg injection) induced prostatic growth by approximately 20%.[1]

The study:
https://www.ncbi.nlm.nih.gov/m/pubmed/17261169/

 

[NewAgeMayan]

This would be receptor specific, just targeting AR's

Dude this sounds way more promising than oral 11kt.

 

[2kvette]

Dude this sounds way more promising than oral 11kt.

Lol, one thing at a time. I'm whipping up the first first batch of KMT any day now. Maybe I'll do it tomorrow...

 

[2kvette]

Dude this sounds way more promising than oral 11kt.

One thing at a time

 

[GreekTheBrick]

Whait a sec. What ever hormone we put in our body will first bind to the SHBG and Albumin and the remainings to the AR. By decreasing SHBG we make more hormone available to bind to AR. Mesterolone, oxandrolone and stanozolol have this trait. Thats the reason we see most advance cyclers to always use proviron as it will enhance any compound with virtually no sides. Contrary to var and winny

 

[2kvette]

Whait a sec. What ever hormone we put in our body will first bind to the SHBG and Albumin and the remainings to the AR. By decreasing SHBG we make more hormone available to bind to AR. Mesterolone, oxandrolone and stanozolol have this trait. Thats the reason we see most advance cyclers to always use proviron as it will enhance any compound with virtually no sides. Contrary to var and winny

Not all steroids have affinity for SHBG. But even with my proposed hypothetical method, the same dose of winny would yield drastically different results.

 

[CatSnake]

Yea it is possible easily, but they just reset. This is why you get those big gains in the first few weeks of a cycle, and then they tapper off. It's because the receptors are literally disappearing!

hmm...

I've read some research that indicated that AR content increases as androgen count increases.... I believe this is part of the initial lag in steroid cycles, as we initially don't have as many AR's available for the rapid increase in androgens.

as far as the taper-off, I believe that's due to an increase in myostatin expression (which typically occurs at 8 weeks or so).

 

[2kvette]

hmm...

I've read some research that indicated that AR content increases as androgen count increases.... I believe this is part of the initial lag in steroid cycles, as we initially don't have as many AR's available for the rapid increase in androgens.

as far as the taper-off, I believe that's due to an increase in myostatin expression (which typically occurs at 8 weeks or so).

This is true as well; in one of the above points AR's I mentioned something about a threshold where they increase. This is what I was talking about.

 

[CatSnake]

This is true as well; in one of the above points AR's I mentioned something about a threshold where they increase. This is what I was talking about.

my bad... I missed that.

here's a study IRT the myostatin issue:

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]