Methylation Of 5AR

[IhateFin]

It has been theorized that finasteride may cause a perminant suppression of 5alpha reductase but I was curious as to why. I also have read many theories that finasteride is capable of changing gene expression and I stumbled on to this article

Abstract 1052: Variable expression of 5-alpha reductase 2 in the aging adult prostate is regulated by DNA methylation | Cancer Research

What if finasteride triggers this same hyper methylation of 5alpha reductase thus silencing it? In this article it stated that treatment with inhitors of this process are able to "reactivate" 5alpha reductase.
The drug that stops the methylation process is azacitidine, but seems super dangerous.

I read an article to stating that 2 polyphenals in caffeine imhibit the methylation too.

Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols. - PubMed - NCBI

Is this the reason it increases 5AR activity?
With information like this what would one recommend in terms of things to research to reduce the gene triggered silence of the 5AR enzyme?
This may not be news to anyone but I thought it was a pretty decent find. I am going to be taking 200mg caffeine pills in hopes to safely inhibit this process and reactivate 5AR.

 

[JoeKool]

Man i can't understand any of that article.

@bloom @TubZy

The results state a treatment reversed the pathway and reactivated SRD5A2

To OP, check this link

http://www.abcam.com/srd5a2-peptide-2-13-ab45681.html

I've been researching it and planning it for myself soon... And will report everything when I do

 

[IhateFin]

Man i can't understand any of that article.

@bloom @TubZy

The results state a treatment reversed the pathway and reactivated SRD5A2

To OP, check this link

SRD5A2 peptide (2-13) (ab45681) | Abcam

I've been researching it and planning it for myself soon... And will report everything when I do

The article is stating that when "Induction of inflammation with lipopolysaccharide" it triggers hypermethalation of 5AR and methlation is a fancy term used to describe controlling of gene expression.
As we know finasteride and PFS leaves many of us in a inflammation like state wheather it's the gut or other areas so what if it triggers this type of inflammation?

Interesting that you have found the 5AR clone peptide. I tried to order this stuff months ago and had no luck. I had $400 worth of 5AR 1&2 clone and a anti-antibody for 5AR and after my order was placed they canceled my order since I'm not with a research lab I was so so close. Don't be surprised if they do the same to you when you try to order it. Maybe @haidut would be able to purchase it since he has a legit lab.
This was the first time I actually was not able to purchase a research chemical for only "research purposes".

If you are able to place the order and they don't cancel it let me know cuz I will be on that so fast hahaha I'll buy thousands of dollars worth of it!! Lol ...but seriously I will

 

[bloom]

It has been theorized that finasteride may cause a perminant suppression of 5alpha reductase but I was curious as to why. I also have read many theories that finasteride is capable of changing gene expression and I stumbled on to this article

Abstract 1052: Variable expression of 5-alpha reductase 2 in the aging adult prostate is regulated by DNA methylation | Cancer Research

What if finasteride triggers this same hyper methylation of 5alpha reductase thus silencing it? In this article it stated that treatment with inhitors of this process are able to "reactivate" 5alpha reductase.
The drug that stops the methylation process is azacitidine, but seems super dangerous.

I read an article to stating that 2 polyphenals in caffeine imhibit the methylation too.

Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols. - PubMed - NCBI

Is this the reason it increases 5AR activity?
With information like this what would one recommend in terms of things to research to reduce the gene triggered silence of the 5AR enzyme?
This may not be news to anyone but I thought it was a pretty decent find. I am going to be taking 200mg caffeine pills in hopes to safely inhibit this process and reactivate 5AR.

@JoeKool
Yeah if you read 'PFS, 5ar and the Brain' all the studies which show that 5ar2 gene expression is under the positive control of Androgens (in rats). So restoration of 5ar2 in theory should be easy, just boost Androgens. The latest study on PFS found blood T/DHT levels were normal compared with controls, with a slight increase in Testosterone. This would suggest 5ar2 expression is fine. However there are many studies which demonstrate that 5ar1 gene expression is negatively controlled by Androgens, but is POSITIVELY controlled by Pituitary hormones. It's all on 'PFS, 5ar and the Brain". As far as srd5a1 or srd5a2 being methylated, and consequently down-regulated? Possible, who knows. Or it could be an impaired Pituitary, causing low levels of Pituitary hormones and consequently low 5ar1 expression. Which is what I'm leaning to. And as far as coffee helping guys with the symptoms of PFS, it's more likely due to it's influence on Brain function and neurotransmission.

Sex hormones metabolism in the brain: influence of central acting drugs on 5 alpha-reduction in rat diencephalon. - PubMed - NCBI

...Diencephalon 5 alpha-reductase activity showed a highly significant increase (p less than 0.01) after a single administration of carbamazepine, reserpine, diazepam, phenytoin, phenobarbital or disulfiram. A significant increase (p less than 0.05) was also found after a single administration of methylphenidate, caffeine or methamphetamine.

 

[IhateFin]

@JoeKool
Yeah if you read 'PFS, 5ar and the Brain' all the studies which show that 5ar2 gene expression is under the positive control of Androgens (in rats). So restoration of 5ar2 in theory should be easy, just boost Androgens. The latest study on PFS found blood T/DHT levels were normal compared with controls, with a slight increase in Testosterone. This would suggest 5ar2 expression is fine. However there are many studies which demonstrate that 5ar1 gene expression is negatively controlled by Androgens, but is POSITIVELY controlled by Pituitary hormones. It's all on 'PFS, 5ar and the Brain". As far as srd5a1 or srd5a2 being methylated, and consequently down-regulated? Possible, who knows. Or it could be an impaired Pituitary, causing low levels of Pituitary hormones and consequently low 5ar1 expression. Which is what I'm leaning to. And as far as coffee helping guys with the symptoms of PFS, it's more likely due to it's influence on Brain function and neurotransmission.

Sex hormones metabolism in the brain: influence of central acting drugs on 5 alpha-reduction in rat diencephalon. - PubMed - NCBI

I don't know if it's that easy otherwise all of propeciahelp would be cured by now.
I will definitely agree more androgens help. That is no doubt. For me proviron cycles and progesterone n androsterone cycles have helped tremendously as well as things like tongkat Ali to the point where I even get a dht itch on my scalp here n there but it's no where near normal and I'm still far from cured :/

Can't wait until I get my hands on supplemental 5AR! Hell if obesity is caused by PUFA and thus heavily suppression DHT and 5AR then maybe a stand alone 5AR clone could be a cure for obesity!!
You heard it here first folks... I'm a genius

 

[sladerunner69]

I don't know if it's that easy otherwise all of propeciahelp would be cured by now.
I will definitely agree more androgens help. That is no doubt. For me proviron cycles and progesterone n androsterone cycles have helped tremendously as well as things like tongkat Ali to the point where I even get a dht itch on my scalp here n there but it's no where near normal and I'm still far from cured :/

Can't wait until I get my hands on supplemental 5AR! Hell if obesity is caused by PUFA and thus heavily suppression DHT and 5AR then maybe a stand alone 5AR clone could be a cure for obesity!!
You heard it here first folks... I'm a genius

More androgens don't help though... that is the opposite of what @bloom is trying get across. Blood level androgens of fin users can be normal or high and they still feel like ***t because higher androgens means lower 5ar1 in the brain and lower GABA (among other important neuro steroids). The key to achieving a better mental state, mood, focus, sleep etc seems to be in increasing GABA, neurosteroids through 5ar1 expression.

 

[bloom]

More androgens don't help though... that is the opposite of what @bloom is trying get across. Blood level androgens of fin users can be normal or high and they still feel like ***t because higher androgens means lower 5ar1 in the brain and lower GABA (among other important neuro steroids). The key to achieving a better mental state, mood, focus, sleep etc seems to be in increasing GABA, neurosteroids through 5ar1 expression.

Couldn't of put it better myself, 5ar2 is just one piece of the puzzle in PFS, and restoration of it theoretically should be easy considering it's gene expression is under the positive control of Androgens. 5ar1 is Another big piece of the puzzle in PFS and restoration of it should be looked into.

 

[IhateFin]

Couldn't of put it better myself, 5ar2 is just one piece of the puzzle in PFS, and restoration of it theoretically should be easy considering it's gene expression is under the positive control of Androgens. 5ar1 is Another big piece of the puzzle in PFS and restoration of it should be looked into.

I was giving it some thought and read some things on another forum and do you think 3a HSD could be an issue as well?
It is needed to metabolize androgens and it's needed to convert DHEA. I always have too much DHEA on my bloods so I bet I'm deficient in this. Forskolin increases this a ton so imma run that at high doses and hcg since that acts as LH as the study I read mention that forskolin needed the addition of LH to amplify the increase of 3a HSD.
I'm also gunna take chologenic acid from green coffee bean since that's supposedly suppresses methlation! Wish me luck!

On top of all that I'll continue 5adhp

 

[bloom]

I was giving it some thought and read some things on another forum and do you think 3a HSD could be an issue as well?
It is needed to metabolize androgens and it's needed to convert DHEA. I always have too much DHEA on my bloods so I bet I'm deficient in this. Forskolin increases this a ton so imma run that at high doses and hcg since that acts as LH as the study I read mention that forskolin needed the addition of LH to amplify the increase of 3a HSD.
I'm also gunna take chologenic acid from green coffee bean since that's supposedly suppresses methlation! Wish me luck!

On top of all that I'll continue 5adhp

3a-hsd could be an issue, but what do you mean by

it's needed to convert DHEA

? from wiki:

3α-hydroxysteroid dehydrogenase (3α-HSD), also known as aldo-keto reductase family 1 member C4, is an enzymethat in humans is encoded by the AKR1C4 gene.[3][4] It is known to be necessary for the synthesis of the endogenousneurosteroids allopregnanolone, THDOC, and 3α-androstanediol. It is also known to catalyze the reversible conversion of 3α-androstanediol (5α-androstane-3α,17β-diol) to dihydrotestosterone (DHT) (5α-androstan-17β-ol-3-one) and vice versa.[5]

 

[IhateFin]

3a-hsd could be an issue, but what do you mean by ? from wiki:

I meant like it's needed to convert DHEA to other androgens.
Even my endo pointed out "it's like it isn't converting"

 

[bloom]

I meant like it's needed to convert DHEA to other androgens.
Even my endo pointed out "it's like it isn't converting"

You mean 3β-HSD, from wiki:

The 3β-HSD complex is responsible for the conversion of:

• Pregnenolone to progesterone
• 17α-Hydroxypregnenolone to 17α-hydroxyprogesterone
• DHEA to androstenedione
• Androstenediol to testosterone
• Androstadienol to androstadienone

Also as far as pituitary hormones increasing 5ar1 activity they're all referenced in the 'PFS, 5ar, and the Brain'. Studies referencing Pituitary hormones, and Oxytocin, and FSH in particular increasing gene expression of 5ar1. Using say LH to increase 5ar1 (if indeed it does) would be a double edged sword since it would increase Testosterone which in turn would decrease 5ar1 expression in the CNS. Read 'PFS, 5ar, and the Brain', all the studies and arguments are there.

 

[IhateFin]

You mean 3β-HSD, from wiki:



Also as far as pituitary hormones increasing 5ar1 activity they're all referenced in the 'PFS, 5ar, and the Brain'. Studies referencing Pituitary hormones, and Oxytocin, and FSH in particular increasing gene expression of 5ar1. Using say LH to increase 5ar1 (if indeed it does) would be a double edged sword since it would increase Testosterone which in turn would decrease 5ar1 expression in the CNS. Read 'PFS, 5ar, and the Brain', all the studies and arguments are there.

Damn it's just a vicious cycle

 

[bloom]

Damn it's just a vicious cycle

It's ok because there are Pituitary Hormones which do not increase Testosterone i.e. Oxytocin. This is what I'm looking into

 

[IhateFin]

It's ok because there are Pituitary Hormones which do not increase Testosterone i.e. Oxytocin. This is what I'm looking into

I've been reading about that stuff. It's said to have a stimulating effect on 5AR. I tried buying some, but couldn't find a reliable source. If you're able to source some let me know! I'd be willing to try it.

I attempted to buy it from a vet website as it comes in like a prettt generous bottle, but it required me to send the prescription of my pet first lol

 

[bloom]

I've been reading about that stuff. It's said to have a stimulating effect on 5AR. I tried buying some, but couldn't find a reliable source. If you're able to source some let me know! I'd be willing to try it.

I attempted to buy it from a vet website as it comes in like a prettt generous bottle, but it required me to send the prescription of my pet first lol

Oxytocin - Wikipedia

The oxytocin peptide is synthesized as an inactive precursor protein from the OXT gene.[16][17][18] This precursor protein also includes the oxytocin carrier protein neurophysin I.[19] The inactive precursor protein is progressively hydrolyzed into smaller fragments (one of which is neurophysin I) via a series of enzymes. The last hydrolysis that releases the active oxytocin nonapeptide is catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM).[20]

The activity of the PAM enzyme system is dependent upon vitamin C (ascorbate), which is a necessary vitamin cofactor. By chance, sodium ascorbate by itself was found to stimulate the production of oxytocin from ovarian tissue over a range of concentrations in a dose-dependent manner.[21] Many of the same tissues (e.g. ovaries, testes, eyes, adrenals, placenta, t

High-dose ascorbic acid increases intercourse frequency and improves mood: a randomized controlled clinical trial. - PubMed - NCBI

Ascorbic acid (AA) modulates catecholaminergic activity, decreases stress reactivity, approach anxiety and prolactin release, improves vascular function, and increases oxytocin release. These processes are relevant to sexual behavior and mood.

 

[IhateFin]

Oxytocin - Wikipedia



High-dose ascorbic acid increases intercourse frequency and improves mood: a randomized controlled clinical trial. - PubMed - NCBI

Ascorbic acid increases oxytocin? Hmm
Have you tried this at all? I'll probs give this a shot

 

[rmgwm]

It has been theorized that finasteride may cause a perminant suppression of 5alpha reductase but I was curious as to why. I also have read many theories that finasteride is capable of changing gene expression and I stumbled on to this article

Abstract 1052: Variable expression of 5-alpha reductase 2 in the aging adult prostate is regulated by DNA methylation | Cancer Research

What if finasteride triggers this same hyper methylation of 5alpha reductase thus silencing it? In this article it stated that treatment with inhitors of this process are able to "reactivate" 5alpha reductase.
The drug that stops the methylation process is azacitidine, but seems super dangerous.

I read an article to stating that 2 polyphenals in caffeine imhibit the methylation too.

Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols. - PubMed - NCBI

Is this the reason it increases 5AR activity?
With information like this what would one recommend in terms of things to research to reduce the gene triggered silence of the 5AR enzyme?
This may not be news to anyone but I thought it was a pretty decent find. I am going to be taking 200mg caffeine pills in hopes to safely inhibit this process and reactivate 5AR.

If you think 5ar has been suppressed then you could take 5ar boosters and see how you feel (Proviron, Sorghum off the top of my head) but I would imagine this has already been tested multiple times by multiple people with limited or little success.

From the stories I've read on this board of PFS it sounds like a complete downregulation of all hormones has occurred, not just 5ar. PFS'ers talk about hypothyroidism, low test, low adrenal output, low estrogen?, low dopamine etc...this is a big clue. When this many things have been downregulated I would tend to lean towards liver damage, brain damage, or an infection (pathogenic, viral, fungal).

If you have low adrenal output as many have reported then I would think taking any type of stimulant like caffeine, even 200 mg would be throwing fuel on the fire. You would probably get a pronounced effect from caffeine at first because you are low on dopamine, which would wear off after a short thirty minutes and then have difficulty sleeping at night, regardless of how early in the morning you took it.

Keep us updated on your findings though, I keep seeing more and more people talk about being affected by finasteride.

 

[IhateFin]

If you think 5ar has been suppressed then you could take 5ar boosters and see how you feel (Proviron, Sorghum off the top of my head) but I would imagine this has already been tested multiple times by multiple people with limited or little success.

From the stories I've read on this board of PFS it sounds like a complete downregulation of all hormones has occurred, not just 5ar. PFS'ers talk about hypothyroidism, low test, low adrenal output, low estrogen?, low dopamine etc...this is a big clue. When this many things have been downregulated I would tend to lean towards liver damage, brain damage, or an infection (pathogenic, viral, fungal).

If you have low adrenal output as many have reported then I would think taking any type of stimulant like caffeine, even 200 mg would be throwing fuel on the fire. You would probably get a pronounced effect from caffeine at first because you are low on dopamine, which would wear off after a short thirty minutes and then have difficulty sleeping at night, regardless of how early in the morning you took it.

Keep us updated on your findings though, I keep seeing more and more people talk about being affected by finasteride.

I have taken those before and proviron has helped with a lot of things! Most notably given me normal ejaculate.

I take 40mg of caffeine. Thank god I solved my cortisol issue but I'm doing so many experiments that I'm always afraid of knocking it out of whack haha

The newest sup I take is chologenic acid which is from green coffee bean extract. It has 40mg caffeine in it.
The reason I take this is due to this study

Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols | Carcinogenesis | Oxford Academic

It shows that this polyphenal can inhibit DNA methylation by 80%