More juice the better?

[tinynate01]

Hey everyone, had a discussion with a friend of mine today. He tends to think the higher amount of doses you do with certain anabolics (dbol, anadrol, anavar, tren etc..) is better. I don't agree just based off personal experience. What do you guys think? Do you guys think it's better to load on the joocey jooce and handfuls of skittles? Or keep it at a moderate amount for recommended dosage?


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[tinynate01]

Maybe. I cruise at 300mg of Test E a week and I might cycle dbol and etc at 20-30mgs but that's it. I never play with more than 2-3 compounds at a time


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[Vision]

Less can be more.. adding a shit ton of compounds is actually a waste for many.. I can use a faction of what most use and just focus on my macros and yield better results..
the key is like seriousness knowing your macros and what adjustments make a crucial effect,only if dudes would truly understand, its all diet man, it really is..

here an read I put together maybe it might help!

Let?s talk AR?s (Androgen receptors) and diminishing gains (studies included)


Lets?s talk AR?s (androgen receptors) ? By Vision
Recently I?ve seen a few questions or concerns regarding AR (androgen receptors) site saturation.. Let me start off by stressing this, it?s a myth that has been regurgitated over the years,it simply does NOT exist. In fact AR?s do NOT down regulate,there?s no such thing as receptor down-regulation (pertaining to AAS usage) in fact with the presence of AAS/Androgens concerning a supraphysiological level they will up-regulate,increasing,and constantly expressing new AR sites THROUGH OUT THE BODY AND TISSUE!.. (However, there is 2-3 culprits that will hinder ones gains when ON cycle, fueling the myth of AR site saturation..?1-Progesterone 2-Mysostatin, 3- and at times E1/E2 estro? but we?ll get to that later)
About the AR

The AR gene principals are to provide instructions for creating proteins called ?androgen receptors?.. As we all know, Andro?s are hormones and the first one that comes to mind is? That?s right, the king,Testosterone?AR?s allow the body to react/respond accordingly to these hormones allowing them to preform their direct action (sexual development,muscle growth and recovery,as well as other strong male sexual characteristics and growth and development)..Receptors are found present throughout the body/tissue..This is where they attach/bind to androgens resulting in AR complex binding to DNA in which regulates the activity of AR genes..DNA is the only thing that can turn the GENE off/on if necessary,NOT AAS!
FYI- AR?s belong to a family of genes known as NR (nuclear hormone receptors), which are proteins that are found within cells that are responsible for sensing steroid hormones, and also play a pivotal role with homeostasis, which finds balance in the endocrine!
Why do my gains seem to diminish after 10-14 weeks?
This study below can explain why our gains tend to become stagnate,or slow down when using Test,deca/primo.. ( IMO this is the ideal time to add an oral such as Dbol,drol,Tbol,Winny,or Var, which predominantly work as a non AR mediated mechanism, unlike Testosterone,Deca,Primo..As these agents express differentiation of the satellite cells of the muscle,maturing muscle cells,thus this is independent of ARs)
Mol Cell Endocrinol. 2009 Apr 10;302(1):26-32. doi: 10.1016/j.mce.2008.12.019. Epub 2009 Jan 21.Measurement of myostatin concentrations in human serum: Circulating concentrations in young and older men and effects of testosterone administration.
Abstract
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.
http://www.ncbi.nlm.nih.gov/pubmed/19356623
Progestin and AR?s
Progesterone has powerful antiadrogenis effect in humans at sufficient levels,capable of decreasing circulating androgens,and estrogen concentraions to castrate levels on both sexes and significantly lowering the expression of the androgen receptor (AR), and the estrogen receptor ? (which posses a pivotal in homeostasis/balance and growth)..
Testosterone and up-regulation!
Testosterone up-regulates androgen receptors and decreases differentiation of porcine myogenic satellite cells in vitro.
Abstract
Accumulation of DNA is essential for muscle growth, yet mechanisms of androgen-induced DNA accretion in skeletal muscle are unclear. The purpose of this study was to determine whether androgen receptors (AR) are present in cultured skeletal muscle satellite cells and myotubes and examine the effects of testosterone on satellite cell proliferation and differentiation. Immunoblot analysis using polyclonal AR antibodies (PG-21) revealed an immunoreactive AR protein of approximately 107 kDa in porcine satellite cells and myotubes. Immunocytochemical AR staining was confined to the nuclei of satellite cells, myotubes, and muscle-derived fibroblasts. Administration of 10(-7) M testosterone to satellite cells, myotubes, and muscle-derived fibroblasts increased immunoreactive AR. In satellite cells and myotubes, AR increased incrementally after 6, 12, and 24 h of exposure to testosterone. Testosterone (10(-10) ? 10(-6) M), alone or in combination with insulin-like growth factor I, basic fibroblast growth factor, or platelet-derived growth factor-BB, had no effect (P > 0.01) on porcine satellite cell proliferation, and testosterone pretreatment for 24 h did not alter the subsequent responsiveness of cells to these growth factors. Satellite cell differentiation was depressed (20-30%) on days 2-4 of treatment with 10(-7) M testosterone. This effect was not reversible within 48 h after treatment withdrawal and replacement with control medium. These data indicate that satellite cells are direct targets for androgen action, and testosterone administration increases immunoreactive AR protein and reduces differentiation of porcine satellite cells in vitro.
http://www.ncbi.nlm.nih.gov/pubmed/8625915
Androgen receptor in rat skeletal muscle: characterization and physiological variations.
Abstract
Androgen binding has been studied in the quadriceps femoris of recently castrated adult and intact immature male and female rats using a variety of techniques for separating and measuring hormone-receptor complexes. [3H]Testosterone, [3H]androstanolone (or 5 alpha-dihydrotestosterone). [3H]methyltrienolone (a potent synthetic androgen), and [3H]estradiol bind to the androgen receptor. Affinities are identical for the first two hormones (Kd = approximately 70 pM) and lower for estradiol (Kd = approximately 0.2 nM), as determined by Scatchard plots of binding data. Competition experiments indicate that in addition to the nonradioactive steroids corresponding to the above-cited tritiated compounds, progesterone, cyproterone acetate (an antiandrogen), and spironolactone compete for [3H]androgen binding by the receptor, but diethylstilbestrol, moxestrol (a potent synthetic steroidal estrogen), and cortisol do not. 3 alpha- and 3 beta-androstanediols slightly inhibit testosterone binding. Therefore, striated muscle androgen receptor specificity is identical to that of all androgen receptors of target tissues which have been previously studied. Binding is abolished by pronase and heat treatment, and displays an approximate 7S sedimentation coefficient in low salt ultracentrifugation gradient analysis. Preliminary observations suggest hormone-induced receptor translocation into the nucleus. No evidence has been found for an independent estrogen receptor. In the course of the binding experiments, extensive metabolism of androstanoloe and testosterone was observed in muscle cytosol at 0-4 C, during the 2-h incubation period used for most binding studies. Metabolite formation can jeopardize the binding data, specifically altering the significance of competition experiments with relatively high concentrations of steroids approaching the Km of metabolizing enzymes. Therefore, most quantitative studies were performed in enzyme-free, receptor-containing cytosol preparations. In adult male rats castrated for 2 days, the concentration of receptor in the cytosol was of the order of 1 fmol/mg protein and corresponded to 72 fmol/mg tissue DNA (that is, 100 and 20 times less than that in corresponding prostatic cytosol, respectively). In the adult female rat 2 days after castration, the concentration of receptor in the cytosol was 0.34 fmol/mg protein. Treatment with testosterone pellets (20 mg for 15 days) increased androgen receptor concentration significantly. In spite of the relatively low concentration of androgen-binding sites, the typical binding specificity of the androgen receptor and the regulatory effects of androgens on their own receptor support the possibility that some effect(s) of androgens upon skeletal muscles may be initiated directly at the cellular level through this receptor, a concept which is also in agreement with recently demonstrated in vitro effects of androgens on cultured myoblasts.
http://www.ncbi.nlm.nih.gov/pubmed/6968675
Steroid receptor phosphorylation: a key modulator of multiple receptor functions.
Abstract
Steroid receptors are hormone-activated transcription factors, the expression and activities of which are also highly dependent upon posttranslational modifications including phosphorylation. The remarkable number of phosphorylation sites in these receptors and the wide variety of kinases participating in their phosphorylation facilitate integration between cell-signaling pathways and steroid receptor action. Sites have been identified in all of the functional domains although the sites are predominantly in the amino-terminal portions of the receptors. Regulation of function is receptor specific, site specific, and often dependent upon activation of a specific cell-signaling pathway. This complexity explains, in part, the early difficulties in identifying roles for phosphorylation in receptor function. With increased availability of phosphorylation site-specific antibodies and better means to measure receptor activities, numerous roles for site-specific phosphorylation have been identified including sensitivity of response to hormone, DNA binding, expression, stability, subcellular localization, and protein-protein interactions that determine the level of regulation of specific target genes. This review summarizes current knowledge regarding receptor phosphorylation and regulation of function. As functional assays become more sophisticated, it is likely that additional roles for phosphorylation in receptor function will be identified.
Pharmacological doses of testosterone upregulated androgen receptor and 3-Beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase and impaired leydig cells steroidogenesis in adult rats.
Abstract
Anabolic androgenic steroids (AAS) are testosterone derivatives originally designed to enhance muscular mass and used for the treatment of many clinical conditions as well as in contraception. Despite popular interest and abuse, we still lack a broad understanding of effects of AAS on synthesis of steroid hormones on the molecular level. This study was designed to systematically analyze the effects of pharmacological/high doses of testosterone on steroidogenic machinery in Leydig cells. Two different experimental approaches were used: (1) In vivo experiment on groups of adult male rats treated with testosterone for 1 day, 2 weeks, and 2 months; (2) Direct in vitro testosterone treatment of Leydig cells isolated from intact rats. Result showed that prolonged in vivo treatment with testosterone decreased the expression of Scarb1 (scavenger receptor class B type 1), Tspo (translocator protein), Star (steroidogenic acute regulatory protein), Cyp11a1 (cholesterol side-chain cleavage enzyme), and Cyp17a1 (17α-hydroxylase/17, 20 lyase) in Leydig cells. Oppositely, the expression of Hsd3b (3-beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase), Ar (androgen receptor), and Pde4a/b (cyclic adenosine monophosphate-dependent phosphodiesterases) was increased. Androgenization for 2 weeks inhibited Cyp19 (aromatase) transcription, whereas 2-month exposure caused the opposite effect. Direct in vitro testosterone treatment also decreased the expression of Cyp11a1, Cyp17a1, and Cyp19a1, whereas Hsd3b was upregulated. The results of expression analysis were supported by declined steroidogenic capacity and activity of Leydig cells, although conversion of pregnenolone to progesterone was stimulated. The upregulation of AR and 3βHSD in testosterone-impaired Leydig cells steroidogenesis could be the possible mechanism that maintain and prevent loss of steroidogenic function.


Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment
Abstract

Androgens stimulate myogenesis, but we do not know what cell types within human skeletal muscle express the androgen receptor (AR) protein and are the target of androgen action. Because testosterone promotes the commitment of pluripotent, mesenchymal cells into myogenic lineage, we hypothesized that AR would be expressed in mesenchymal precursor cells in the skeletal muscle. AR expression was evaluated by immunohistochemical staining, confocal immunofluorescence, and immunoelectron microscopy in sections of vastus lateralis from healthy men before and after treatment with a supraphysiological dose of testosterone enanthate. Satellite cell cultures from human skeletal muscle were also tested for AR expression. AR protein was expressed predominantly in satellite cells, identified by their location outside sarcolemma and inside basal lamina, and by CD34 and C-met staining. Many myonuclei in muscle fibers also demonstrated AR immunostaining. Additionally, CD34+ stem cells in the interstitium, fibroblasts, and mast cells expressed AR immunoreactivity. AR expression was also observed in vascular endothelial and smooth muscle cells. Immunoelectron microscopy revealed aggregation of immunogold particles in nucleoli of satellite cells and myonuclei; testosterone treatment increased nucleolar AR density. In enriched cultures of human satellite cells, more than 95% of cells stained for CD34 and C-met, confirming their identity as satellite cells, and expressed AR protein. AR mRNA and protein expression in satellite cell cultures was confirmed by RT-PCR, reverse transcription and real-time PCR, sequencing of RT-PCR product, and Western blot analysis. Incubation of satellite cell cultures with supraphysiological testosterone and dihydrotestosterone concentrations (100 nm testosterone and 30 nm dihydrotestosterone) modestly increased AR protein levels. We conclude that AR is expressed in several cell types in human skeletal muscle, including satellite cells, fibroblasts, CD34+ precursor cells, vascular endothelial, smooth muscle cells, and mast cells. Satellite cells are the predominant site of AR expression. These observations support the hypothesis that androgens increase muscle mass in part by acting on several cell types to regulate the differentiation of mesenchymal precursor cells in the skeletal muscle.

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]
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The final analysis, the conclusion!

Now that we?ve read the studies and what science has demonstrated and well articulated in the installations, I feel its fair to say that AR down regulation does not exist in the presence of Androgen?s,and furthermore to speculate that AR?s as a perennial position for the androgen ligand.. Truth (supported by medical journals world wide) AR?s up-regulate,increasing,and constantly expressing new AR sites THROUGH OUT THE BODY AND TISSUE!

(articles in medicine/science suggest the following)
When unattached to an androgen they have a half life of approximately three hours and are ultimately replaced with new ones. However, in the presence of an androgen (i.e. when they?re attached), they become more sensitive, their half life is doubled and the amount of new receptors being formed also increases substantially. It?s also important to remember that AR-mediated effects are not the whole story when it comes to anabolic steroid activity in the body. There are still a host of other effects that have little to nothing at all to do with AR, known as non-AR dependent effects, which include central nervous system stimulation and a host of other anabolic and potentially anabolic activities. But that still leaves us with the question of why our gains seem to slow down after a few cycles, and why we need to keep upping the dose. In truth, the answer probably has more to do with the body attempting to return to homeostasis through other mechanisms than it has with the androgen receptor.
I hope this brings some clarification to the subject!
Vision
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[theCaptn']

I under perform on too much gear. Lethargy, high bp, short breath, loss of appetite, poor sleep.

 

[muscleicon]

Same here Captn'.

Icon

 

[zionoir626]

I under perform on too much gear. Lethargy, high bp, short breath, loss of appetite, poor sleep.

More is better then you DIE!!

 

[tinynate01]

I under perform on too much gear. Lethargy, high bp, short breath, loss of appetite, poor sleep.

I experience the same thing, loss of sleep and short breath is a big definite with me lol


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[Vision]

I under perform on too much gear. Lethargy, high bp, short breath, loss of appetite, poor sleep.

Exactly the quality of life just diminishes.... it's about finding the happy medium, and let me tell you it took me a very long time to figure out whats my "zone"...

Lower dosage is and longer blasts...

 

[Usealittle]

I under perform on too much gear. Lethargy, high bp, short breath, loss of appetite, poor sleep.

i feel like this on any amount of anadrol... i stick to dbol

 

[mnmsnowbeast]

Every ones body's are different,age,muscle mass,body type,eto,endo,meso,whatever you are,if it was my first ever cycle,just take the min. so you don't saturate your receptors,as anything that takes repetitive protocol,you will of course need more to do the same as your first trip down the AAS street. But if you take all the advice you can from so many forums,that stress,blood work to see where you are,and if what you took was any good,than you can run the proper PCT or TRT to rekick start your system.

 

[Vision]

i feel like this on any amount of anadrol... i stick to dbol

Real Iranians do this to me, I love them but I hate them

 

[Standard Donkey]

more aas = more gains and side effects. gains do not increase in a linear fashion, diminishing returns applies. take a gram of test a week for 4 month blasts/400mg/week for 2 month cruises with proper AI, track your lifts and your macros (adjust these as you progress), and you will be surprised how much progress you will make.

 

[bayou boy]

Nice read

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