Enzyme question progesterone allopreg 3α-Hydroxysteroid dehydrogenase

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cdraham
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Re: Enzyme question progesterone allopreg 3α-Hydroxysteroid dehydrogenase

Unread post by cdraham »

Copper wrote: Mon Aug 23, 2021 7:13 pm Fluoxetine is said to induce 3a-HSD, but what this study says is it instead inhibits reverse oxidation back to 5a-DHP. So it's not clear in what way it happens

RoDH - Retinol Dehydrogenase - enzyme is affected by also Isotretinoin, the drug that causes post accutane syndrome. Some of PSSD patients like me that are having more prominent neurological symptoms show many similarities with PAS patients. I think this is could be why.

- https://www.pasforum.info/forums/theories-of-pas.9/

- https://bpspubs.onlinelibrary.wiley.com ... /bph.12891


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Sigma receptors are interesting topic and I think they should be talked about as well. "Neurosteroids" (especially Progesterone) binds to sigma-1. They modulate "intracellular calcium signalling", through IP3r. Also they modulate the "SERT" and "5HT2C" receptors (inhibits dopamine and noradreline) too.

DMT and DXM is agonist at sigma-1, and I think this could be why some got better after trying Ayahuasca (even cured) or DXM. (You should never take DXM regardless)

- https://en.m.wikipedia.org/wiki/Sigma-1_receptor

- viewtopic.php?f=20&t=648&p=5524&hilit=Ayahuasca#p5524
Sigma is very interesting, this fits my personal research too. Out of anything i got the biggest emotional window from DXM. I tried ketamine and psychedelics and its obvious to me the reason dxm worked was becsuse of sigma1 agonism
cdraham
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Re: Enzyme question progesterone allopreg 3α-Hydroxysteroid dehydrogenase

Unread post by cdraham »

But if progesterone is a sigma agonist, and DXM is too, why would DXM give a window. My understanding is we have high Progesterone, it upregulates 5ht2c etc and stops dopamine and Ne release, so a sigma agonist would upregulate it furher??
cdraham
Posts: 448
Joined: Thu Jul 04, 2019 10:39 am
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Re: Enzyme question progesterone allopreg 3α-Hydroxysteroid dehydrogenase

Unread post by cdraham »

cdraham wrote: Tue Aug 24, 2021 5:36 am But if progesterone is a sigma agonist, and DXM is too, why would DXM give a window. My understanding is we have high Progesterone, it upregulates 5ht2c etc and stops dopamine and Ne release, so a sigma agonist would upregulate it furher??
Oh well i found this

Inflammatory cytokines upregulate 5-HT2C receptors and the SERT, and sigma-1 agonists block the effects cytokines have on serotonin reuptake and 5-HT2C receptor sensitivity.

Yeah this seems to fit. Inflammation from unknown source and sigma agonism restores 5ht2c which modulates dopamine and NE which is essential for hedonic response. This was my experience also. Just where does high progesterone fit in here. If progesterone is a sigma agonist, and we have high Progesterone, it should help us feel better

Edit: high progesterone seems to downregulate sigma receptors over time, so this seems to fit even more
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