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Mental Health
The role of neurosteroids in post-traumatic stress disorder and alcohol use disorder
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<blockquote data-quote="madman" data-source="post: 273757" data-attributes="member: 13851"><p><em><strong>*Testosterone is the main androgen circulating in humans.47 <u>It modulates neuronal excitability via genomic and non-genomic mechanisms</u>.47 <u>Testosterone upregulates the expression of neuropeptide Y (NPY), a neuropeptide with anti-stress effects</u>.48,49 Additionally, metabolites of testosterone (e.g., 3α-androstanediol) may positively affect GABAA function.30</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Estradiol, the primary endogenous form of estrogen, is most potent during pre-menopause 50 and is converted from testosterone via aromatase enzymes. Estradiol is produced primarily in the gonads, as well as other organs, including the heart, brain, and skin.50 <u>Estradiol signal throughout the body via classic nuclear (slow) receptors (ERα and ERβ), as well as more rapidacting receptors (e.g., GPR30 and ER-X)</u>.50 <u>Estradiol has been shown to have anxiolytic-like effects and to potentiate fear extinction via binding to both ERα and ERβ</u>.30,51 <u>Furthermore, estradiol modulates the serotonergic system, as well as the activity of the HPA axis</u>.41</strong> <strong><u>Estradiol inhibits the expression of the serotonin transporter (SERT), thereby increasing the time serotonin is available to signal in the synapse</u>.52</strong> <strong><u>Estradiol also modulates levels of adrenocorticotropic hormone (ACTH) and cortisol via actions on glucocorticoid and CRH signaling</u>.28 <u>Preclinical evidence also shows that estradiol modulates the release of dopamine in the striatum and nucleus accumbens via binding to membrane estradiol receptors</u>, most notably in female rodents.53,54</strong> </em></p><p><em></em></p><p><em>*<em><strong><u>In particular, progesterone, allopregnanolone, and pregnanolone have positive modulatory effects on GABAA receptors, which result in increased GABAergic signaling</u>.29,39 This increase in GABA transmission may be advantageous in the treatment of stress-related disorders, as well as alcohol use and GABAergic agents are emerging as a promising treatment target for concurrent PTSD and AUD.32</strong> </em></em></p></blockquote><p></p>
[QUOTE="madman, post: 273757, member: 13851"] [I][B]*Testosterone is the main androgen circulating in humans.47 [U]It modulates neuronal excitability via genomic and non-genomic mechanisms[/U].47 [U]Testosterone upregulates the expression of neuropeptide Y (NPY), a neuropeptide with anti-stress effects[/U].48,49 Additionally, metabolites of testosterone (e.g., 3α-androstanediol) may positively affect GABAA function.30 *Estradiol, the primary endogenous form of estrogen, is most potent during pre-menopause 50 and is converted from testosterone via aromatase enzymes. Estradiol is produced primarily in the gonads, as well as other organs, including the heart, brain, and skin.50 [U]Estradiol signal throughout the body via classic nuclear (slow) receptors (ERα and ERβ), as well as more rapidacting receptors (e.g., GPR30 and ER-X)[/U].50 [U]Estradiol has been shown to have anxiolytic-like effects and to potentiate fear extinction via binding to both ERα and ERβ[/U].30,51 [U]Furthermore, estradiol modulates the serotonergic system, as well as the activity of the HPA axis[/U].41[/B] [B][U]Estradiol inhibits the expression of the serotonin transporter (SERT), thereby increasing the time serotonin is available to signal in the synapse[/U].52[/B] [B][U]Estradiol also modulates levels of adrenocorticotropic hormone (ACTH) and cortisol via actions on glucocorticoid and CRH signaling[/U].28 [U]Preclinical evidence also shows that estradiol modulates the release of dopamine in the striatum and nucleus accumbens via binding to membrane estradiol receptors[/U], most notably in female rodents.53,54[/B] *[I][B][U]In particular, progesterone, allopregnanolone, and pregnanolone have positive modulatory effects on GABAA receptors, which result in increased GABAergic signaling[/U].29,39 This increase in GABA transmission may be advantageous in the treatment of stress-related disorders, as well as alcohol use and GABAergic agents are emerging as a promising treatment target for concurrent PTSD and AUD.32[/B] [/I][/I] [/QUOTE]
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Mental Health
The role of neurosteroids in post-traumatic stress disorder and alcohol use disorder
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