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Thyroid, Pregnenolone, Progesterone, DHEA, etc
Thyroid, DHEA, Pregnenolone, Progesterone, etc
Pregnenolone 101: What You Need to Know About this Precursor Hormone
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<blockquote data-quote="Nelson Vergel" data-source="post: 239511" data-attributes="member: 3"><p><h3>The study used 400 mg (one dose)</h3><p></p><h3>Drug Administration</h3><p>Study drug (pregnenolone) and matching placebo identical in appearance were obtained from Belmar Pharmacy (Lakewood, CO), which provided certificates of analysis. Participants were randomly assigned to receive a single oral dose of 400 mg pregnenolone (n=16), or placebo (n=15). Participants and investigators were blind to condition. Pregnenolone was administered as a precursor loading strategy to significantly increase downstream allopregnanolone levels. Pregnenolone is lipophilic and readily crosses the blood brain barrier. We have previously found that pregnenolone is preferentially metabolized to allopregnanolone, rather than other compounds such as cortisol or DHEA (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648625/#R43" target="_blank">43</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648625/#R44" target="_blank">44</a>); however these metabolites were also assayed. Allopregnanolone serum levels have been reported to triple two hours after oral administration of 400 mg pregnenolone (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648625/#R45" target="_blank">45</a>). Thus, drug administration occurred two hours before neuroimaging to ensure elevated levels during the scan.</p><h3>Results</h3><p>Compared to placebo, allopregnanolone was associated with reduced activity in the amygdala and insula across all conditions. During the appraisal condition, allopregnanolone increased activity in the dorsal medial prefrontal cortex and enhanced connectivity between the amygdala and dorsal medial prefrontal cortex, an effect that was associated with reduced self-reported anxiety.</p><h3>Conclusions</h3><p><strong>These results demonstrate that in response to emotional stimuli, allopregnanolone reduces activity in regions associated with generation of negative emotion.</strong> Furthermore, allopregnanolone may enhance activity in regions linked to regulatory processes. Aberrant activity in these regions has been linked to anxiety psychopathology. <strong>These results thus provide initial neuroimaging evidence that allopregnanolone may be a target for pharmacological intervention in the treatment of anxiety disorders, and suggest potential future directions for research into neurosteroid effects on emotion regulation neurocircuitry.</strong></p><h3><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648625/" target="_blank">Allopregnanolone Elevations Following Pregnenolone Administration are Associated with Enhanced Activation of Emotion Regulation Neurocircuits</a></h3></blockquote><p></p>
[QUOTE="Nelson Vergel, post: 239511, member: 3"] [HEADING=2]The study used 400 mg (one dose)[/HEADING] [HEADING=2]Drug Administration[/HEADING] Study drug (pregnenolone) and matching placebo identical in appearance were obtained from Belmar Pharmacy (Lakewood, CO), which provided certificates of analysis. Participants were randomly assigned to receive a single oral dose of 400 mg pregnenolone (n=16), or placebo (n=15). Participants and investigators were blind to condition. Pregnenolone was administered as a precursor loading strategy to significantly increase downstream allopregnanolone levels. Pregnenolone is lipophilic and readily crosses the blood brain barrier. We have previously found that pregnenolone is preferentially metabolized to allopregnanolone, rather than other compounds such as cortisol or DHEA ([URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648625/#R43']43[/URL], [URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648625/#R44']44[/URL]); however these metabolites were also assayed. Allopregnanolone serum levels have been reported to triple two hours after oral administration of 400 mg pregnenolone ([URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648625/#R45']45[/URL]). Thus, drug administration occurred two hours before neuroimaging to ensure elevated levels during the scan. [HEADING=2]Results[/HEADING] Compared to placebo, allopregnanolone was associated with reduced activity in the amygdala and insula across all conditions. During the appraisal condition, allopregnanolone increased activity in the dorsal medial prefrontal cortex and enhanced connectivity between the amygdala and dorsal medial prefrontal cortex, an effect that was associated with reduced self-reported anxiety. [HEADING=2]Conclusions[/HEADING] [B]These results demonstrate that in response to emotional stimuli, allopregnanolone reduces activity in regions associated with generation of negative emotion.[/B] Furthermore, allopregnanolone may enhance activity in regions linked to regulatory processes. Aberrant activity in these regions has been linked to anxiety psychopathology. [B]These results thus provide initial neuroimaging evidence that allopregnanolone may be a target for pharmacological intervention in the treatment of anxiety disorders, and suggest potential future directions for research into neurosteroid effects on emotion regulation neurocircuitry.[/B] [HEADING=2][URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648625/']Allopregnanolone Elevations Following Pregnenolone Administration are Associated with Enhanced Activation of Emotion Regulation Neurocircuits[/URL][/HEADING] [/QUOTE]
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Thyroid, Pregnenolone, Progesterone, DHEA, etc
Thyroid, DHEA, Pregnenolone, Progesterone, etc
Pregnenolone 101: What You Need to Know About this Precursor Hormone
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