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Testosterone Replacement, Low T, HCG, & Beyond
Blood Test Discussion
Desperate advice needed quickly..too late?
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<blockquote data-quote="madman" data-source="post: 223454" data-attributes="member: 13851"><p>[URL unfurl="true"]https://www.excelmale.com/forum/threads/improving-diagnostic-accuracy-and-treatment-decisions-in-men-with-hypogonadism.24968/[/URL]</p><p></p><p><strong><em>post #5</em></strong>.....sit back and think more deeply!</p><p></p><p><strong>29:33-31:33</strong></p><p></p><p><em><strong>*cFTV/cFTZ (EAM/TruT)</strong></em></p><p></p><p><strong><em>* most of the linear equations underestimate free testosterone concentrations</em></strong></p><p></p><p></p><p></p><p>You are and always will be clueless when it comes to testosterone's binding to SHBG!</p><p></p><p>If it were only so simple.....LMFAO!</p><p></p><p>The new dynamic model leads to the reconsideration of several dogmas related to testosterone's binding to SHBG and has important physiologic and clinical implications.</p><p></p><p><strong><em>*First, the fraction of circulating testosterone that is free is <u>substantially greater (2.9±0.4%)</u></em></strong><em> <strong>than has been generally assumed (% cFTV 1.5±0.4%)</strong>.</em></p><p><em></em></p><p><em><strong>*Second, <u>percent FT is not significantly related to total testosterone over a wide range of total testosterone concentrations</u>. However, the percent FT declines as SHBG concentrations increase, although it <u>does not decline as precipitously as predicted by Vermeulen's model</u>. <u>Due to the allostery between the two binding sites, SHBG is able to regulate FT levels in a much larger dynamic range</u>.</strong></em></p><p></p><p></p><p>Key points:</p><p></p><p><strong>EAM (cFTZ) SHBG: T binding</strong></p><p><strong></strong></p><p><strong><em>*</em></strong><em><strong>Intra-dimer complex allostery suggests that<u> SHBG can regulate FT fraction over a wide range of total testosterone concentrations without getting saturated</u>.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Indeed, it was found that percent FT calculated using the new model <u>changed very modestly over a wide range of total testosterone concentrations</u>.</strong></em></p><p></p><p><strong><em>*Due to the allostery between the two binding sites, <u>SHBG is able to regulate FT levels in a much larger dynamic range</u>.</em></strong></p><p><strong><em></em></strong></p><p><strong><em></em></strong></p><p><strong><em></em></strong></p><p><strong><em></em></strong></p><p><strong><em></em></strong></p><p><strong><em><strong>*<u>Free testosterone concentration is ideally measured using the equilibrium dialysis method, performed under standardized conditions</u>.1,31<u> Direct tracer analog methods for measuring free testosterone concentrations are inaccurate, and therefore, their use is not recommended</u>.35 Although several equations to estimate free testosterone concentration from total testosterone, SHBG, and albumin concentrations have been published,36-38 the estimation of free testosterone concentration performed using these equations is predicated upon accurate measurements of total testosterone, SHBG, and albumin concentrations.31,35 <u>Furthermore, equations that are based on a linear model of testosterone’s binding to SHBG assume a fixed binding affinity (approximately 1 nM)31 and ignore the competing presence of other sex steroids, such as dihydrotestosterone and estradiol</u>.</strong></em></strong></p><p><strong><em><strong></strong></em></strong></p><p><strong><em><strong>*Recent studies using modern biophysical techniques have suggested that the <u>binding of testosterone and estradiol to an SHBG dimer is a dynamic process that involves allosteric interactions between binding sites on each of the 2 SHBG monomers such that the binding affinities of the 2 sites are not equivalent</u>.36,39 <u>The binding of a ligand to the first monomer influences the conformational and energetic states of both the monomers</u>.39 <u>The estimation of free testosterone concentration based on an ensemble allosteric model provides a close approximation of concentrations measured using equilibrium dialysis</u>36;</strong></em></strong></p><p><strong><em><strong></strong></em></strong></p><p><strong><em><strong>*<u>the computations of free testosterone concentrations using the ensemble allostery model can be obtained at <a href="https://tru-t.org/" target="_blank">TruT Free Testosterone Calculator by FPT</a></u>. Because of dynamic changes in the binding affinity of SHBG upon ligand binding, depending on the ligand and SHBG concentrations, <u>no equation can accurately estimate free testosterone concentration under all conditions</u>.39</strong></em></strong></p></blockquote><p></p>
[QUOTE="madman, post: 223454, member: 13851"] [URL unfurl="true"]https://www.excelmale.com/forum/threads/improving-diagnostic-accuracy-and-treatment-decisions-in-men-with-hypogonadism.24968/[/URL] [B][I]post #5[/I][/B].....sit back and think more deeply! [B]29:33-31:33[/B] [I][B]*cFTV/cFTZ (EAM/TruT)[/B][/I] [B][I]* most of the linear equations underestimate free testosterone concentrations[/I][/B] You are and always will be clueless when it comes to testosterone's binding to SHBG! If it were only so simple.....LMFAO! The new dynamic model leads to the reconsideration of several dogmas related to testosterone's binding to SHBG and has important physiologic and clinical implications. [B][I]*First, the fraction of circulating testosterone that is free is [U]substantially greater (2.9±0.4%)[/U][/I][/B][I] [B]than has been generally assumed (% cFTV 1.5±0.4%)[/B]. [B]*Second, [U]percent FT is not significantly related to total testosterone over a wide range of total testosterone concentrations[/U]. However, the percent FT declines as SHBG concentrations increase, although it [U]does not decline as precipitously as predicted by Vermeulen's model[/U]. [U]Due to the allostery between the two binding sites, SHBG is able to regulate FT levels in a much larger dynamic range[/U].[/B][/I] Key points: [B]EAM (cFTZ) SHBG: T binding [I]*[/I][/B][I][B]Intra-dimer complex allostery suggests that[U] SHBG can regulate FT fraction over a wide range of total testosterone concentrations without getting saturated[/U]. *Indeed, it was found that percent FT calculated using the new model [U]changed very modestly over a wide range of total testosterone concentrations[/U].[/B][/I] [B][I]*Due to the allostery between the two binding sites, [U]SHBG is able to regulate FT levels in a much larger dynamic range[/U]. [B]*[U]Free testosterone concentration is ideally measured using the equilibrium dialysis method, performed under standardized conditions[/U].1,31[U] Direct tracer analog methods for measuring free testosterone concentrations are inaccurate, and therefore, their use is not recommended[/U].35 Although several equations to estimate free testosterone concentration from total testosterone, SHBG, and albumin concentrations have been published,36-38 the estimation of free testosterone concentration performed using these equations is predicated upon accurate measurements of total testosterone, SHBG, and albumin concentrations.31,35 [U]Furthermore, equations that are based on a linear model of testosterone’s binding to SHBG assume a fixed binding affinity (approximately 1 nM)31 and ignore the competing presence of other sex steroids, such as dihydrotestosterone and estradiol[/U]. *Recent studies using modern biophysical techniques have suggested that the [U]binding of testosterone and estradiol to an SHBG dimer is a dynamic process that involves allosteric interactions between binding sites on each of the 2 SHBG monomers such that the binding affinities of the 2 sites are not equivalent[/U].36,39 [U]The binding of a ligand to the first monomer influences the conformational and energetic states of both the monomers[/U].39 [U]The estimation of free testosterone concentration based on an ensemble allosteric model provides a close approximation of concentrations measured using equilibrium dialysis[/U]36; *[U]the computations of free testosterone concentrations using the ensemble allostery model can be obtained at [URL='https://tru-t.org/']TruT Free Testosterone Calculator by FPT[/URL][/U]. Because of dynamic changes in the binding affinity of SHBG upon ligand binding, depending on the ligand and SHBG concentrations, [U]no equation can accurately estimate free testosterone concentration under all conditions[/U].39[/B][/I][/B] [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Blood Test Discussion
Desperate advice needed quickly..too late?
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