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Benefits of Androgenic Compounds.

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  • Benefits of Androgenic Compounds.

    Benefits of the much derided androgenic compounds.

    What purpose do androgenic compounds serve that have little anabolic effect, especially if they are associated with many adverse effects such as prostate enlargement/cancer, hair loss, etc.?

    Anabolic compounds bind to the nuclear androgen receptor, which then enters the cellular nucleus and alters the expression of genes leading to the “genomic” effects of increased protein synthesis and anabolic hypertrophy in skeletal muscle tissue. The processes of genetic transcription, translation of amino acids, the formation of proteins and their incorporation into muscle tissue takes time. It does not happen immediately. However, it is well known that androgens also have “nongenomic” effects, many of which take place very quickly, almost immediately. These nongenomic effects are not mediated by the nuclear androgen receptor, but by rapidly acting receptors located on the surface of the cellular membrane. These membrane androgen receptors are G-protein coupled receptors, and some of them have recently be identified, such as GPRC6A. These receptors produce rapid changes in cellular activity through various mechanisms, many of which are still not fully understood. Androgens also produce nongenomic effects including increased strength by interacting with protein kinase receptors, such as the EGF receptor, see, for example: Dihydrotestosterone activates the MAPK pathway and modulates maximum isometric force through the EGF receptor.

    It is known that androgens can rapidly increase intracellular calcium levels, which leads to an immediate increase muscular contractile force, improves neuromuscular efficiency, and dramatically decreases muscular fatigue in fast-twitch fibers. Androgens also have an effect on fat cells, signalling them to burn fat to supply energy to skeletal muscle, and signaling muscle cells to uptake more glucose providing the needed increased muscular energy. Although not a rapid effect, androgens also affect precursor cells, shifting their differentiation from the lipogenic lineage to the myogenic lineage, which just means that more of these precursor cells become muscle tissue and fewer become fat tissue. See: Androgens stimulate myogenic differentiation and inhibit adipogenesis.

    Additionally, androgens have rapid psychological effects. Many believe that the benefit of taking androgenic compounds just prior to a workout comes from the mental sense of increased “aggression”. We all know that mental attitude is very important for having a good, effective workout; but androgens also have a very direct and profound physiological effect on strength, fatigue and body composition independent of their mental effects.

    The “aggression”, increased strength, and decreased fatigue all contribute to a better workout, greater mechanical stimulation of muscular tissue, which ultimately lead to greater anabolic growth. Futhermore, androgenic compounds, through various mechanisms, alter body composition, by decreasing fat stores as well as increasing muscular growth. This is why androgenic compounds are particularly useful in cutting cycles.

  • #2
    Thanks for breaking this down as you did. Answered some questions that I've had for awhile.

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    • #3
      Cool study.VX1! I took a look at it and what is really getting me excited is how a physiological doses of dht not only increase force but activate the ERK pathway in both fast and slow twitch muscle fibers. Before Datbtrue went away i was looking at ways to activate ERK pathway because it leads to mgf production and proliferation according to Dat. This could be another "nongenomic" effect.
      Inspector Jacques Clouseau: "There is a time to laugh and a time not to laugh, and this is not one of them."

      "If i want to use a suppliment i take steroids"- Stomp

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      • #4
        Originally posted by Kluso View Post
        Cool study.VX1! I took a look at it and what is really getting me excited is how a physiological doses of dht not only increase force but activate the ERK pathway in both fast and slow twitch muscle fibers. Before Datbtrue went away i was looking at ways to activate ERK pathway because it leads to mgf production and proliferation according to Dat. This could be another "nongenomic" effect.
        You're right. Androgens, like DHT, activate the MAPK/ERK pathway through a transmembrane receptor, not the nuclear AR. Activating this pathway is a nongenomic effect, which ultimately leads to downstream genomic effects, including increased cell proliferation. This is not always good, since this pathway is implicated in cancer in the prostate and other tissues. Another effect of this pathway is activation of Nf-κb, which can lead to inflammatory conditions. Without a doubt one beneficial effect of ERK pathway activation is that it prevents neurons from dying preventing age-related cognitive decline and even Alzheimer's Disease.
        See:

        Androgen receptor-mediated non-genomic regulation of prostate cancer cell proliferation

        Testosterone enhances lipopolysaccharide-induced interleukin-6 and macrophage chemotactic protein-1 expression by activating the extracellular signal-regulated kinase 1/2/nuclear factor-κB signalling pathways in 3T3-L1 adipocytes

        Androgens Keep Your Brain Healthy

        Two Androgen Response Elements have been identified in the IGF1 upstream promoter; but these AREs have binding domains for the nuclear AR, independent of the ERK pathway. In other words, androgens promote IGF1 expression via the classical nuclear AR, which is a genomic effect of androgens. They may also increase IGF1 expression thru nongenomic pathways, like the MAPK/ERK pathway, though I haven't seen any research on this possible effect.
        MGF is a hypothetical splice variant of IGF1. Research has been done using an artificially synthesized peptide: but to the best of my knowledge, it has never been found in any living organism, nor has a receptor for it ever been found. So, I am very skeptical about it. I haven't done any research on this topic in many years, so If you have more up-to-date information about the possible existence of a naturally occuring MGF peptide and the role it plays in natural physiology, I would be interested in seeing it. Thanks.
        For more information about MGF, see:


        Mechano-Growth Factor: A Putative Product of IGF-I Gene Expression Involved in Tissue Repair and Regeneration

        Last edited by vx1; 08-25-2017, 12:04 PM.

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        • #5
          From my understanding mgf is a real igf1 splice variant that is responsible for muscle cell proliferation. From what i understand mgf is used by the cell it was created and taking exo mgf will never work like native mgf because it cannot get inside the cell. So all the research Goldspink did to get the BB community all excited is bunk because he assumed it would get into the cell. Like you said there is no known receptor and as far as i know they still havent found one. So instead of injecting mgf we should be looking at ways to increase our own production. And from what i understand that is thru the ERK pathway.
          Last edited by Kluso; 08-25-2017, 02:48 PM.
          Inspector Jacques Clouseau: "There is a time to laugh and a time not to laugh, and this is not one of them."

          "If i want to use a suppliment i take steroids"- Stomp

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          • #6
            Thanks for the explanation Kluso. As I said, I haven't really studied this topic in years. It appears that the 2010 article I referenced is outdated, at least insofar as the existence of the naturally occurring peptide is concerned. If, as you say, intracellular MGF is what matters, as far as muscle tissue is concerned only MGF within satellite cells would matter, not in the cells of muscle fiber. This is because MGF promotes proliferation and differentiation, and satellite cells are the only ones that can do this. Myofibers don't differentiate or proliferate. This raises some interesting questions. Satellite cells aren't directly affected by mechanical stimulation of muscle since they do not contract, etc. They simply remain quiescent until activated. So if MGF mediates the effects of exercise on muscle growth, there must be a signaling pathway from the contractile myofibers to the satellite cells. Another question is how does MGF floating about in the cytoplasm cause the nuclear changes in gene transcription that ultimately result in proliferation and differentiation. Understanding these pathways is important because interventions might then be found to activate those same pathways, possibly even bypassing MGF. Nuclear receptors are located in the cytoplasm until they bind with their ligand and then translocate to the nucleus in order to directly change gene expression. But MGF doesn't have any corresponding receptors. The MAPK/ERK pathway is really a large family of different pathways all of which send signals from the cell membrane to the nucleus changing gene expression. Many different compounds can activate these pathways with many different genetic effects. Some signaling molecule from the contractile myofibers could, indeed, activate an MAPK/ERK pathway, which could result in increased expression of MGF. If we knew what that signaling molecule was we might be able to dispense with exercising, and just take the molecule. The remaining question is how the increased amount of MGF in the cytoplasm changes genetic transcription. I imagine it could act as a transcription factor, but it would still need to be transported into the nucleus to affect the gene expressions necessary for proliferation and differentiation. How does that happen? It is also kind of hard to believe that a single transcription factor could be responsible for such a dramatic change in cellular activity, which would require radical changes in the expression of many hundreds of different genes. Also, what factors determine whether the cell proliferates or differentiates? Many questions remain, though some of these may already have been answered. If Kluso or anyone else has further information, I would find it very interesting. Thanks again.

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