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Testosterone Replacement, Low T, HCG, & Beyond
Blood Test Discussion
Hope for an accurate method to determine Free Testosterone
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<blockquote data-quote="Blackhawk" data-source="post: 111867" data-attributes="member: 16042"><p><span style="color: #333333">Hope this is not too much a tangent. Just the assumption: "only the free fraction is biologically active" is not completely true. While it still remains especially very important in the context of low SHBG, there may be newer thinking coming on this</span></p><p><span style="color: #333333"></span></p><p><span style="color: #333333"></span><span style="color: #333333">"only the free fraction is biologically active" </span></p><p><span style="color: #333333"></span></p><p><span style="color: #333333"></span><span style="color: #333333">This is apparently false when it comes to sex hormone sensitive tissues including prostate, breast and endometrium. It wasn't stated comprehensively which tissues are affected, but it is likely to be more, like potentially testicle cells, ovary etc. See Nick Sakas video with Jay Campbell: </span>https://www.youtube.com/watch?v=a9sbWHAmVrA</p><p></p><p>I took notes. still have to go back and proof them based on what Sakas says, but here's a rough summary:</p><p></p><p>SHBG: proteins produced in liver bind T and estrogens. </p><p></p><p>Estimated 2-3% of sex hormones unbound.</p><p></p><p>1980's researchers used non hormone responsive cultured cells in vitro and added T E2 and SHBG. When adding SHBG, steroid hormones had no effect on the cells. They concluded that SHBG made sex hormones ineffective.</p><p></p><p>Free hormone hypothesis based on this stated SHBG interferes with sex hormone uptake of cells. There was no other known benefit of SHBG.</p><p></p><p>However, in 2005 researchers proved that tissue specific receptors exist which SHBG binds to, then Sex hormones trigger downstream reactions/responses in the cells leading to gene expression inside the cell. This is mediated by a messenger molecule; CMP cyclic adenosine mono phosphate which can active specific Kinases and is also involved in regulation of adrenaline and glucagon.</p><p></p><p>This creates a nongenomic pathway of signaling gene and protein expression inside the cell.</p><p></p><p>In contrast,Testosterone attaching to cell androgen receptors is a genomic pathway.</p><p></p><p>The implication is in the case of these specific cell types, the T and E2/SHBG complexes are effective attaching to their specific receptors and affecting cellular process despite being bound to SHBG. This dispells some of the free T hypothesis.</p><p></p><p>Also found megalin a receptor of LDL protein family which sequesters vitamins A and D inside the cell, then the ligands are free after binding molecules are broken down so Vit A & D can exert their role in the cell. Megalin can also sequester the complex of SHBG and sex steroids. This is another genomic pathway of SHBG/sex hormone complex signaling inside the cell.</p><p></p><p>There is another implication from other researchers who spotted a receptor named chubalin(?) which does not actively internalize SHBG and sex hormones, it serves as a receptor for albumin which also binds to steroid hormones,</p><p></p><p>These things mean we may need to change how we assess SHBG levels in relationship to sex hormone metabolism.</p><p></p><p></p><p></p><p>I am going to try to get a list of the references he cites.</p></blockquote><p></p>
[QUOTE="Blackhawk, post: 111867, member: 16042"] [COLOR=#333333]Hope this is not too much a tangent. Just the assumption: "only the free fraction is biologically active" is not completely true. While it still remains especially very important in the context of low SHBG, there may be newer thinking coming on this [/COLOR][COLOR=#333333]"only the free fraction is biologically active" [/COLOR][COLOR=#333333]This is apparently false when it comes to sex hormone sensitive tissues including prostate, breast and endometrium. It wasn't stated comprehensively which tissues are affected, but it is likely to be more, like potentially testicle cells, ovary etc. See Nick Sakas video with Jay Campbell: [/COLOR]https://www.youtube.com/watch?v=a9sbWHAmVrA I took notes. still have to go back and proof them based on what Sakas says, but here's a rough summary: SHBG: proteins produced in liver bind T and estrogens. Estimated 2-3% of sex hormones unbound. 1980's researchers used non hormone responsive cultured cells in vitro and added T E2 and SHBG. When adding SHBG, steroid hormones had no effect on the cells. They concluded that SHBG made sex hormones ineffective. Free hormone hypothesis based on this stated SHBG interferes with sex hormone uptake of cells. There was no other known benefit of SHBG. However, in 2005 researchers proved that tissue specific receptors exist which SHBG binds to, then Sex hormones trigger downstream reactions/responses in the cells leading to gene expression inside the cell. This is mediated by a messenger molecule; CMP cyclic adenosine mono phosphate which can active specific Kinases and is also involved in regulation of adrenaline and glucagon. This creates a nongenomic pathway of signaling gene and protein expression inside the cell. In contrast,Testosterone attaching to cell androgen receptors is a genomic pathway. The implication is in the case of these specific cell types, the T and E2/SHBG complexes are effective attaching to their specific receptors and affecting cellular process despite being bound to SHBG. This dispells some of the free T hypothesis. Also found megalin a receptor of LDL protein family which sequesters vitamins A and D inside the cell, then the ligands are free after binding molecules are broken down so Vit A & D can exert their role in the cell. Megalin can also sequester the complex of SHBG and sex steroids. This is another genomic pathway of SHBG/sex hormone complex signaling inside the cell. There is another implication from other researchers who spotted a receptor named chubalin(?) which does not actively internalize SHBG and sex hormones, it serves as a receptor for albumin which also binds to steroid hormones, These things mean we may need to change how we assess SHBG levels in relationship to sex hormone metabolism. I am going to try to get a list of the references he cites. [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Blood Test Discussion
Hope for an accurate method to determine Free Testosterone
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