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Clinical Use of Anabolics and Hormones
Clinical Use of Anabolics and Hormones
Nandrolone for Mood | Feeling much Better..
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<blockquote data-quote="tareload" data-source="post: 222614"><p>No rodents here...</p><p></p><p>[URL unfurl="true"]https://academic.oup.com/eurjpc/article/21/8/1049/5925802[/URL]</p><p></p><p><strong><span style="font-family: 'Arial'"><em>Here we show that supra-physiological concentrations of testosterone inhibit the urinary excretion of NO in healthy volunteers 48 hours after the administration of testosterone. Since urinary NO is a biomarker for endothelial function and mainly originates from the endothelium, our results indicate that even a single dose of testosterone may induce a decrease in NO formation in endothelial cells. One determinant of NO bioavailability is the expression and activity of eNOS, the main enzyme involved in the metabolism of NO in endothelial cells. Here we show that testosterone down-regulates the gene expression of eNOS after 48 hours. In a previous study it was shown that low doses of testosterone induce the protein expression and activity of eNOS in HUVECs and in rat aorta. These effects were lost when higher doses of testosterone were used, and in agreement with our findings, an inhibition in eNOS expression and activity could be discerned.</em></span></strong><span style="font-family: 'Arial'"><em><a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank"><strong>16</strong></a></em></span></p><p><span style="font-family: 'Arial'"><em></em></span></p><p><span style="font-family: 'Arial'"><em>Since addition of the antioxidant SeMe partly abolished the inhibitory effect of testosterone on eNOS gene expression, we speculate that oxidative stress may at least to some extent explain the transcriptional inhibition of eNOS and subsequently the NO production. Therefore we further studied whether supra-physiological doses of testosterone induce oxidative stress in vivo. Indeed, this turned out to be right as the results revealed an inhibition of the antioxidative capacity in vivo probably by generation of reactive oxygen species (ROSs) and/or inhibition of the antioxidative activity. This would be in line with our in vitro results where several important defence enzyme genes, that is, CAT, SOD1 and GPX4, were down-regulated by a supra-physiological dose of testosterone. The decreased transcriptional activity was observed already after 8 h exposure, indicating that oxidative stress may be acutely induced by testosterone. However, after 48 h the mRNA expression levels of these enzyme genes were back to baseline levels or increased, possibly as a consequence of the induced oxidative pressure in the endothelial cells. <strong>Our results indicate that the oxidative stress status was induced by testosterone both in the in vivo situation and in vitro. A previous study in rats has shown that AAS induce oxidative stress. After eight weeks of stanozolol treatment the serum levels of thiobarbituric acid-reactive substances (TBARSs) increased.</strong><a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank"><strong>17</strong></a></em></span></p><p><span style="font-family: 'Arial'"><em></em></span></p><p><span style="font-family: 'Arial'"><em>It is well known that long term AAS abuse has detrimental effects on the cardiovascular system, to which the increase of LDL and decrease of HDL may contribute. However, many adverse side-effect observations are based on anecdotal evidences and the available scientific data are scarce. It is therefore important to scientifically identify and characterize the side-effects of AASs.<strong><a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">18</a></strong> <strong>Despite the liability of AAS abusers to develop cardiovascular disorders the AAS-related effects on the endothelium have received little attention. D'Ascenzo et al. demonstrated that exposure of HUVECs to AAS alters endothelial cell growth with a strong anti-proliferative effect, induces apoptosis and modifies intracellular levels of calcium.<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">9</a> Two studies have observed that the flow mediated dilatation of the brachial artery determined by ultrasound (an in vivo index of endothelial function) was reduced in body builders using AASs.<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">8</a>,</strong><a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank"><strong>19</strong></a></em></span></p><p></p><p><u><span style="font-size: 18px"><span style="font-family: 'Arial'"><em><strong>The baseline serum testosterone concentration in the study population was 5 ng/ml.<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">20</a> This is the same as has been seen in other study groups similar in respect of age, gender and ethnicity.<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">21</a> Two days after testosterone administration the serum testosterone level has increased by 200%. The concentration used in our in vitro experiments (1 µM) is in the range of the levels achieved after administration of testosterone to the volunteers.<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">20</a> In this study we have expressly studied supra-physiological doses of testosterone in order to mimic AAS-abuse. <u>It is important to stress that testosterone exerts the opposite effect when therapeutic doses of it are used in hypogonadal men.</u></strong> Male hypogonadism has been associated with endothelial dysfunction<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">22</a> and the decline in testosterone has been associated with metabolic syndrome.<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">23</a> Testosterone replacement therapy (TRT) has been shown to have beneficial effects on the endothelium.<a href="https://www.excelmale.com/forum/javascript%3A;" target="_blank">24</a></em></span></span></u></p><p></p><p><span style="font-family: 'Arial'"><em><em>It is important to address the limitations of this study since it was conducted in relatively few individuals and after only a single testosterone dose. <strong>The results observed here do not necessarily imply that repeated AAS abuse exerts these detrimental effects, or even worsens endothelial function. It is possible that chronic adaptations develop to counterbalance the increased level of oxidative stress or the acute reduction of eNOS mRNA and NO production. The data need to be verified in other studies. However, it is difficult to study the adverse side-effects of AAS abuse in humans because of the ethical restraints limiting the amount of administered testosterone. Retrospective studies from self-reported AAS abusers are sometimes indicative but have a lot of limitations, such as co-administration of other drugs, purity and identity of the AASs, etc.</strong></em></em></span></p><p></p><p></p><p><u>Rodent Free, #cuttheshit for [USER=18514]@DS3[/USER] </u></p><p></p><p>FYI [USER=38109]@Cataceous[/USER]</p><p></p><p>[USER=15235]@Guided_by_Voices[/USER] Sure would be fun to follow this experiment (~2000 ng/dl TT) out a few years and look at transfer function between <u>micro</u> and <u>macro</u> toxicity for my graph. Makes me rethink how to present the data.</p><p></p><p><img src="https://aws1.discourse-cdn.com/tnation/uploads/default/original/4X/1/d/9/1d9e5a9c223c60427e499213b2dc10699a59aad3.png" class="bbImage" alt="" data-url="https://aws1.discourse-cdn.com/tnation/uploads/default/original/4X/1/d/9/1d9e5a9c223c60427e499213b2dc10699a59aad3.png" style="" /></p></blockquote><p></p>
[QUOTE="tareload, post: 222614"] No rodents here... [URL unfurl="true"]https://academic.oup.com/eurjpc/article/21/8/1049/5925802[/URL] [B][FONT=Arial][I]Here we show that supra-physiological concentrations of testosterone inhibit the urinary excretion of NO in healthy volunteers 48 hours after the administration of testosterone. Since urinary NO is a biomarker for endothelial function and mainly originates from the endothelium, our results indicate that even a single dose of testosterone may induce a decrease in NO formation in endothelial cells. One determinant of NO bioavailability is the expression and activity of eNOS, the main enzyme involved in the metabolism of NO in endothelial cells. Here we show that testosterone down-regulates the gene expression of eNOS after 48 hours. In a previous study it was shown that low doses of testosterone induce the protein expression and activity of eNOS in HUVECs and in rat aorta. These effects were lost when higher doses of testosterone were used, and in agreement with our findings, an inhibition in eNOS expression and activity could be discerned.[/I][/FONT][/B][FONT=Arial][I][URL='https://www.excelmale.com/forum/javascript%3A;'][B]16[/B][/URL] Since addition of the antioxidant SeMe partly abolished the inhibitory effect of testosterone on eNOS gene expression, we speculate that oxidative stress may at least to some extent explain the transcriptional inhibition of eNOS and subsequently the NO production. Therefore we further studied whether supra-physiological doses of testosterone induce oxidative stress in vivo. Indeed, this turned out to be right as the results revealed an inhibition of the antioxidative capacity in vivo probably by generation of reactive oxygen species (ROSs) and/or inhibition of the antioxidative activity. This would be in line with our in vitro results where several important defence enzyme genes, that is, CAT, SOD1 and GPX4, were down-regulated by a supra-physiological dose of testosterone. The decreased transcriptional activity was observed already after 8 h exposure, indicating that oxidative stress may be acutely induced by testosterone. However, after 48 h the mRNA expression levels of these enzyme genes were back to baseline levels or increased, possibly as a consequence of the induced oxidative pressure in the endothelial cells. [B]Our results indicate that the oxidative stress status was induced by testosterone both in the in vivo situation and in vitro. A previous study in rats has shown that AAS induce oxidative stress. After eight weeks of stanozolol treatment the serum levels of thiobarbituric acid-reactive substances (TBARSs) increased.[/B][URL='https://www.excelmale.com/forum/javascript%3A;'][B]17[/B][/URL] It is well known that long term AAS abuse has detrimental effects on the cardiovascular system, to which the increase of LDL and decrease of HDL may contribute. However, many adverse side-effect observations are based on anecdotal evidences and the available scientific data are scarce. It is therefore important to scientifically identify and characterize the side-effects of AASs.[B][URL='https://www.excelmale.com/forum/javascript%3A;']18[/URL][/B] [B]Despite the liability of AAS abusers to develop cardiovascular disorders the AAS-related effects on the endothelium have received little attention. D'Ascenzo et al. demonstrated that exposure of HUVECs to AAS alters endothelial cell growth with a strong anti-proliferative effect, induces apoptosis and modifies intracellular levels of calcium.[URL='https://www.excelmale.com/forum/javascript%3A;']9[/URL] Two studies have observed that the flow mediated dilatation of the brachial artery determined by ultrasound (an in vivo index of endothelial function) was reduced in body builders using AASs.[URL='https://www.excelmale.com/forum/javascript%3A;']8[/URL],[/B][URL='https://www.excelmale.com/forum/javascript%3A;'][B]19[/B][/URL][/I][/FONT] [U][SIZE=18px][FONT=Arial][I][B]The baseline serum testosterone concentration in the study population was 5 ng/ml.[URL='https://www.excelmale.com/forum/javascript%3A;']20[/URL] This is the same as has been seen in other study groups similar in respect of age, gender and ethnicity.[URL='https://www.excelmale.com/forum/javascript%3A;']21[/URL] Two days after testosterone administration the serum testosterone level has increased by 200%. The concentration used in our in vitro experiments (1 µM) is in the range of the levels achieved after administration of testosterone to the volunteers.[URL='https://www.excelmale.com/forum/javascript%3A;']20[/URL] In this study we have expressly studied supra-physiological doses of testosterone in order to mimic AAS-abuse. [U]It is important to stress that testosterone exerts the opposite effect when therapeutic doses of it are used in hypogonadal men.[/U][/B] Male hypogonadism has been associated with endothelial dysfunction[URL='https://www.excelmale.com/forum/javascript%3A;']22[/URL] and the decline in testosterone has been associated with metabolic syndrome.[URL='https://www.excelmale.com/forum/javascript%3A;']23[/URL] Testosterone replacement therapy (TRT) has been shown to have beneficial effects on the endothelium.[URL='https://www.excelmale.com/forum/javascript%3A;']24[/URL][/I][/FONT][/SIZE][/U] [FONT=Arial][I][I]It is important to address the limitations of this study since it was conducted in relatively few individuals and after only a single testosterone dose. [B]The results observed here do not necessarily imply that repeated AAS abuse exerts these detrimental effects, or even worsens endothelial function. It is possible that chronic adaptations develop to counterbalance the increased level of oxidative stress or the acute reduction of eNOS mRNA and NO production. The data need to be verified in other studies. However, it is difficult to study the adverse side-effects of AAS abuse in humans because of the ethical restraints limiting the amount of administered testosterone. Retrospective studies from self-reported AAS abusers are sometimes indicative but have a lot of limitations, such as co-administration of other drugs, purity and identity of the AASs, etc.[/B][/I][/I][/FONT] [U]Rodent Free, #cuttheshit for [USER=18514]@DS3[/USER] [/U] FYI [USER=38109]@Cataceous[/USER] [USER=15235]@Guided_by_Voices[/USER] Sure would be fun to follow this experiment (~2000 ng/dl TT) out a few years and look at transfer function between [U]micro[/U] and [U]macro[/U] toxicity for my graph. Makes me rethink how to present the data. [IMG]https://aws1.discourse-cdn.com/tnation/uploads/default/original/4X/1/d/9/1d9e5a9c223c60427e499213b2dc10699a59aad3.png[/IMG] [/QUOTE]
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Clinical Use of Anabolics and Hormones
Clinical Use of Anabolics and Hormones
Nandrolone for Mood | Feeling much Better..
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