Neuroactive steroids and neurosteroidogenesis

General Discussion
#2

Neurosteroids and GABA-A Receptor Function

Now this is important

Neurosteroids are synthesized in glial cells and neurons of the central and peripheral nervous system from cholesterol or steroidal precursors imported from peripheral sources (Schumacher et al., 2000; Baulieu et al., 2007)

It mean that RAW material are:
1- DHT
2-Cholesterol
Please put attention to this:

Biosynthesis of allopregnanolone and pregnenolone sulfate (PS) from cholesterol within the neuron or glial cell . Enzymes involved are P450 side-chain cleavage (P450scc), 3α-hydroxysteroid dehydrogenase (3α-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD) and 5α-reductase. Transport of cholesterol across the mitochondrial membrane is enhanced by the steroidogenic acute-regulatory (StAR) protein and the mitochondrial benzodiazepine receptor (MBR). 5α-DHP represents 5α-dihydroprogesterone

This is even more interesting

Replacing the hydrogen of hydroxyl with methyl, thus eliminating the ability of the steroid to donate a hydrogen bond in this region, results in dramatic reduction in its potency ----->(This sound to me PFS).

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#3

I am posting here some studies about Neurosteroidogenesis, I encourage to read and learn about it maybe it can help us to find therapeutic alternative.

Neurosteroidogenesis Today: Novel Targets for Neuroactive Steroid Synthesis and Action and Their Relevance for Translational Research.

#4

Targeting neurosteroidogenesis as therapy for PTSD

#5

Ethanol Enhances Neurosteroidogenesis in Hippocampal Pyramidal Neurons by Paradoxical NMDA Receptor Activation

eurosteroidogenesis today: Novel targets for neuroactive steroid synthesis and action and their relevance for translational research

#6

Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes

https://www.pnas.org/content/96/23/13512

#8

Therapeutic strategies to increase neurosteroidogenesis

https://www.researchgate.net/figure/Therapeutic-strategies-to-increase-neurosteroidogenesis-and-improve-PTSD-by-enhancing_fig1_259768034

#9

I’m not so sure about the study on SSRIs. It’s saying that fluoxetine inhibits the reaction that creates allopregnenolone but I remember reading and posting one a few months ago that said the exact opposite. Unless I’m misinterpreting the study

#10

This is the one I’m talking about

#11

Then why not try one more pill of fin @MOONCHILD

#12

Are there any studies that show that boosting 3a-HSD alone through SSRIs can downregulate AR through depletion of DHT and 5ar metabolites?

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#13

From what I’ve skimmed, that study was talking about fluoxetine inhibiting the reverse oxidative reaction of allo back to 5a-DHP, leading to more allo in the brain, but only for female rats for some reason.

When I tried microdose prozac, it didn’t help my insomnia but made me feel calm, warm, and fuzzy. Like taking a hit of morphine.

For the sake of my own life, I really need a safe way to help me sleep through the night again. I am really on thin ice. Even 4-5 hours at a time would be a blessing. People have tried the TSPO ligand etifoxine for neurosteroidogenesis to not much fanfare but its toxic side effects are terrifying. The only other drug like etifoxine with TSPO binding affinity was alpidem and it was removed from the market due to severe liver damage.

Glycine at 3g before bedtime makes my insomnia even worse. Doubt upping it to 6g would make it better.

At the moment I’m trying gelsemium at 20ch homeopathic dose i.e. sugar pills and not enough strychnine-related alkaloids that supposedly raises neurosteroids.

I wonder how safe it is to take 3a-DHP. At the end of the day as it’s been retreaded constantly, isn’t it about how to get our AR back online in order for normal production of 3a-HSD in homeostasis?

#14

I primarily suffering from a mental side of PFS: anxiety, panic attacks. My psychatrist prescribed me a SSRI (paroxetin). I can assure you it gave me a good relief from my symptoms (along with side effects of SSRI). So I really believe in the theory that SSRI can increase neurosteroid levels.

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#15

Have you tried tryptophan. It knocks me out like nothing else.

#16

The insomnia is my worst side. I am struggling to stay asleep for even close to two hours. Can’t even go back to sleep afterwards. How much tryptophan should I take?

#17

I remember that my fist side effect was sleep problem, maybe fixing this problem, will fix the rest of the problems
I found in a study that say:
Sleep disturbances such as insomnia increase risk for psychiatric disorders
and for sure psychiatric disorders probably are going to kill you dick and libido.
But the solution is not sleeping pills, the solution is to find what is killing our sleep.

One of the studies say that was found lack of neurogenesis on PSF ( of course neurogenesis need own body stem cell to differentiate to neurons)
Now this other study say
Stem cells need time to sleep

#18

No kidding. Insomnia will shut you down completely and systematically and give you heart disease and cancer. I am literally feeling suicidal right now. I don’t want to end up like the other users here. I am desperate to pull the trigger on mirtazapine but I’m really scared of it provoking PSSD and/or PLMD/sleep myoclonus to get triple Mercked.

#19

Mercked calm down Brother, we are going to get out of this at some point, while still life there is hope.
hang in there.

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#20

Steroids, stress and the gut microbiome-brain axis

Moreover, immune responses to pathogenic bacteria produce cytokines and lymphokines that can affect brain physiology.15 Because the nervous system is a master regulator of host function, this allows microbes to influence a broad range of complex physiological processes. An improved mechanistic understanding of how bacterial molecules act on the nervous system could yield improved therapeutics for treating behavioural and neurological disorders.16

Although gonadal steroids can alter the gut microbiota, it appears that, in turn, the gut microbiome can influence hormone levels.34 In postmenopausal women, gut microbiota diversity was positively associated with the ratio of oestrogen metabolites.

Note: Alterations of gut microbiome composition was found in the PFS Italy study.

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#21

I stopped taking VSL and feel worse. My bowel movements are so loose and unhealthy. Our guts play such a bigger role in this and our general health than people realize.

I’ve also had nasty insomnia. Feel like I’m never really sleeping

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#22

Ethanol Enhances Neurosteroidogenesis in Hippocampal Pyramidal Neurons by Paradoxical NMDA Receptor Activation

I wonder how many of us still drinking alcohol ? Because I am not.