skull
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This report kind of bothers me --I found part of it in some studies that where done but there seems to be some "broteligence 'mixed in--If it proves to be true then that would suck--it means you cant use t3 while on IGF? '--------------------------------------------------------------------------------
The Problem with T3
For a long time we have known that thyroid hormones played a role in gene transcription during myoblast proliferation and differentiation. The regulation of gene expression by thyroid hormone (T3) involves binding of the hormone to nuclear receptors [thyroid hormone receptor (TR)] acting as T3-dependent transcription factors encoded by TRalpha (NR1A1) and TRbeta (NR1A2) genes. This in turn leads to the desired increase in the SERCA1 and SERCA2a mRNA proteins we all want because these cod for the Ca++ pumps on the muscle cell that cause use to burn extra calories through increased active Ca++ transport. However new research in spring 2006 revealed an regulatory mechanism that might not make you so happy. In this study, they identified another transcript, TRalpha-DeltaE6, produced by alternative splicing with microexon 6b instead of exon 6. This splicing leads to the synthesis of a protein devoid of a hinge domain. And what this new factor was found to be responsible for was that although TRalpha-DeltaE6 did not bind DNA, its expression induced a TRalpha1 sequestration in the cytoplasm. Functional studies demonstrated that TRalpha-DeltaE6 inhibits the transcriptional activity of TRalpha1 and retinoic X receptor-alpha, but not of retinoic acid receptor-alpha. We also found that TRalpha-DeltaE6 efficiently decreased the ability of TRalpha to inhibit MyoD transcriptional activity during myoblast proliferation. Consequently, when overexpressed (like when people take synthetic T3) in myoblasts, it stimulated terminal differentiation. This suggest that TRalpha-DeltaE6 may act as down regulator of overall T3 receptor activity, including its ability to repress MyoD transcriptional activity during myoblast proliferation.
OK what did I just say????
By taking T3 you basically up regulate a regulatory mechanism that regulates the effect of T3 not by effecting the adult muscle cells, but it actually kills off you muscle stem cells before they have a chance to join with the adult muscle cell. These are the same cells that MGF and IGF and anabolic steroids increase, and are the same cells that your body recruits for growth and repair.
In addition say you take MGF, and IGF, and anabolic steroids with your T3 to try and combat this effect. (btw I have no research to suggest these would significantly help the situation and people that say they lose less by using them may be an alternative mechanism etc. so you still might be losing the effect of recruitment of muscle stem cells)
T3 up regulates these SERCA1 proteins right. Here is a question that always bothered me, because these proteins have a long half life and t3 itself isn’t increasing your metabolism like a stimulant… you shouldn’t need to slowly come off it. It should be that the slow loss of the CA++ pumps would serve as a slow decline on its own. Here in lies the other problem. Your body responds to up regulated SERCA1 proteins with another group of hormones to catabolize them. Corticosteroids!!! Like the all famous cortisol.
This is done in part by the corticosteroids causing an increase in sarcolipin mRNA which decrease the activity of the SERCA1 pumps. So not only are you losing the energy burning pumps after you come off t3, you are decreasing the effectiveness and levels of the ones you naturally would have and your increasing corticosteroid levels. That makes for a hell of a rebound effects….
The Problem with T3
For a long time we have known that thyroid hormones played a role in gene transcription during myoblast proliferation and differentiation. The regulation of gene expression by thyroid hormone (T3) involves binding of the hormone to nuclear receptors [thyroid hormone receptor (TR)] acting as T3-dependent transcription factors encoded by TRalpha (NR1A1) and TRbeta (NR1A2) genes. This in turn leads to the desired increase in the SERCA1 and SERCA2a mRNA proteins we all want because these cod for the Ca++ pumps on the muscle cell that cause use to burn extra calories through increased active Ca++ transport. However new research in spring 2006 revealed an regulatory mechanism that might not make you so happy. In this study, they identified another transcript, TRalpha-DeltaE6, produced by alternative splicing with microexon 6b instead of exon 6. This splicing leads to the synthesis of a protein devoid of a hinge domain. And what this new factor was found to be responsible for was that although TRalpha-DeltaE6 did not bind DNA, its expression induced a TRalpha1 sequestration in the cytoplasm. Functional studies demonstrated that TRalpha-DeltaE6 inhibits the transcriptional activity of TRalpha1 and retinoic X receptor-alpha, but not of retinoic acid receptor-alpha. We also found that TRalpha-DeltaE6 efficiently decreased the ability of TRalpha to inhibit MyoD transcriptional activity during myoblast proliferation. Consequently, when overexpressed (like when people take synthetic T3) in myoblasts, it stimulated terminal differentiation. This suggest that TRalpha-DeltaE6 may act as down regulator of overall T3 receptor activity, including its ability to repress MyoD transcriptional activity during myoblast proliferation.
OK what did I just say????
By taking T3 you basically up regulate a regulatory mechanism that regulates the effect of T3 not by effecting the adult muscle cells, but it actually kills off you muscle stem cells before they have a chance to join with the adult muscle cell. These are the same cells that MGF and IGF and anabolic steroids increase, and are the same cells that your body recruits for growth and repair.
In addition say you take MGF, and IGF, and anabolic steroids with your T3 to try and combat this effect. (btw I have no research to suggest these would significantly help the situation and people that say they lose less by using them may be an alternative mechanism etc. so you still might be losing the effect of recruitment of muscle stem cells)
T3 up regulates these SERCA1 proteins right. Here is a question that always bothered me, because these proteins have a long half life and t3 itself isn’t increasing your metabolism like a stimulant… you shouldn’t need to slowly come off it. It should be that the slow loss of the CA++ pumps would serve as a slow decline on its own. Here in lies the other problem. Your body responds to up regulated SERCA1 proteins with another group of hormones to catabolize them. Corticosteroids!!! Like the all famous cortisol.
This is done in part by the corticosteroids causing an increase in sarcolipin mRNA which decrease the activity of the SERCA1 pumps. So not only are you losing the energy burning pumps after you come off t3, you are decreasing the effectiveness and levels of the ones you naturally would have and your increasing corticosteroid levels. That makes for a hell of a rebound effects….
