Reversing silenced AR signal with demethylating agents - A promising treatment option?


#401

Here is another very interesting article that discusses a breakthrough in the understanding of demthylation:
sciencedaily.com/releases/2011/06/110630122001.htm

The key idea is that researchers have discovered that dethylation can be an active process controlled by a specific protein called thymine DNA glycosylase (or TDG). TDG needs a second protein to demethylate DNA, so the researchers speculate that this knowledge could help us in the future to develop therapies to demethylate specific genes.


#402

Great articles RunningMan, i really enjoyed reading those especially the one about Dot1. Hopefully awor’s study will shed further light on this angle and we can start investigating further.


#403

good idea. Only Awor is doing some thing practical. Can you write to university proffessors about this?
Please some thing concrete other wise many good ideas will die here in the forum.


#404

sp, the studies Runningman linked were performed by cancer researchers at well renowned institutions, that’s pretty damn hard concrete the way I see it.


#405

This could potentially be a method to manipulate DNA encoding the proteins that control methylation status:

http://en.wikipedia.org/wiki/Zinc_finger_nuclease

Zinc-finger nucleases (ZFNs) are artificial restriction enzymes generated by fusing a zinc finger DNA-binding domain to a DNA-cleavage domain. Zinc finger domains can be engineered to target desired DNA sequences and this enables zinc-finger nucleases to target unique sequences within complex genomes. By taking advantage of endogenous DNA repair machinery, these reagents can be used to precisely alter the genomes of higher organisms.

My GP mentioned this to me during a discussion regarding the epigenetic theory of persistent 5ARI side effects. He actually showed an interest in what I had to say! Must have been some of the “fresh out of med school” enthusiasm shining through.

It’s a little frightening thinking about what could go wrong during a therapy like this one though.


#406

I cant believe ppl buy into this…


#407

Good for you. You don’t have to buy into it. Go spend your time and money looking into other possible causes while we waste ours discussing crazy science fictiony theories that are based on “logic” and being studied by “university researchers” using “science”, oooooh. What do they know! right?
I’m sure the cure is somewhere on the shelves at GNC.


#408

It looks like methylation testing is now commercially available:
epigendx.com/methylation.html

I assume that this type of test is already part of awor’s research project, but it’s good to know that these tests are becoming more accessible to us.


#409

Let me recap:

and

Absolutely clearly! Jokes aside, he was not denying it before he looked over his records. After looking at his records, he’s denying it.

Aaah, the old posts accidentally deleted…

I’m not taking it personal. But I think this is an important thing to determine – i.e. whether or not all males for whom TRT doesn’t work took a 5ARI. I’m just saying that you cannot ignore what chilln found out looking at his records.


#410

m_18

I don’t know man here is what he sent me 5 days ago

“I may have taken saw palmetto. I trialled the use of natural isolate supplements to boost my testosteone for a few years before commencing hormone modulation therapy, but I have very little memory of all of the over 100 supplements I trialled, other than to say that none of them had a sustained effect (longer than two weeks).”
I had other emails from him about 8-9 months ago as well. after my mailbox got full I had to delete. maybe I still have his some pms still.

that said don’t want to continue this arguments any more now.
For me the simple question is Awor and Whalen72 were already on TRT before using Fin, absolutely no problem with their TRT. then what brought them here?
I had PMs from a Guy ( about six months ago or more, I don’t remember now, on musclechatroom or messmorphosis.com) he was on TRT for many years then used fin+betasitosterol and his TRT stopped working. He was very depressed and suicidal.Then he suddenly stopped pming me , I don’t know the reason. I will try to find his PMs and will share here.

here is another one

I am curious, you mentioned Beta Sitosterol, which I have taken as well as FINISTRIDE (propecia .25 mg daily for about a year) for hair loss. (which now i know was due to hypothyroid) so I stopped that.

I am on HRT as well as thyroid meds, & adrenal fatigue and i am having problem with transdermal Testosterone Cream just not working, so my doc says sometimes this happens and JUST now put me on cypoinate and hcg.

So my question is how does Beta Sitosterol affect T or maybe it doesn’t? Then would the propecia cause problems with my HRT as well.

Please tell me your angle on the Beta Sitosterol, saw palmetto, propecia, hair loss creams, etc… how does this affect things in regards to HRT, thyroid and adrenal fatigue?

Thanks for you input!

Read more from the MESO-Rx Steroid Forum at: forum.mesomorphosis.com/private.php?do=showpm&pmid=1829671#ixzz1TH6cXPRT


#411

I am open to the epigenetics theory, but also skeptical because so many of us have had partial recoveries and times when we felt 100% fixed…

I have had my genome mapped out and can look at all the SNPs of the AR gene, but I do not think that helps with epigenetical change…

Anyways, it is said that the AR gene is responsible for autism traits. I honestly have felt from day 1 of my crash that I fell A LOT more autistic than I did prior to the crash, but I have sort of just chalked this up to the adrenal insufficiency.

I

=======================
learn.genetics.utah.edu/content/epigenetics/nutrition/

Nutrients that effect epigenetics (wouldnt hurt to get these tested)

Nutrient - epigenetic role
Methionine - SAM synthesis
Folic Acid - Methionine synthesis
Vitamin b12 - Methionine synthesis
Vitamin b6 - Methionine synthesis
SAM-e - Enzymes transfer methyl groups from SAM directly to the DNA
choline - Methyl donor to SAM
Betaine - Break down the toxic byproducts of SAM synthesis
Resveratrol - Removes acetyl groups from histones, improving health (shown in lab mice)
Genestein - Increased methylation, cancer prevention, unknown mechanism
Sulforafane - Increased histone acetylation turning on anti-cancer genes
Butyrate - Increased histone acetylation turning on ‘protective’ genes, increased lifespan (shown in the lab in flies)
Diallyl sulphide (DADS) - Increased histone acetylation turning on anti-cancer genes


#412

Youve had you genome mapped? ???

First you accuse Mew of being a Merck employee, then it turns out you have been posting on BB forums for 7yrs without mentioning Fin/Sp as the cause of your problems, and now this. Seriously think your bad news.


#413
  1. Oscar the Grouch, I think I can say with with 100% certainty that you are the most annoying poster here. What the fuck have you done to help others out here other that nitpick and complain about anything anyone ever posts.

  2. Yes, I have. It’s not hard to do these days and is relatively inexpensive. I found out that I am twice as likely to get prostate cancer among many other things.

  3. Posting on BB.com? I think not. Maybe you meant Dr Crisler’s board? I have wasted 5+ years and $4,000+ on Dr. Crisler. It wasn’t until I found this board and put 2 + 2 together…

  4. I used Saw Palmetto not Propecia, which is also why it probably took so long to figure out…

  5. I said jokingly that “Mew can act like he doesnt want anyone to find an answer to this”. I specifically said it was a joke and then specifically said that I am thankful for all he does here.

I even “snap shot” some of my AR gene. Check it out attached to this post.



#414

Oh yeah! Well, whatever. You post a load of rubbish all over the place. I dont trust you.


#415

Hahahaha, you don’t trust him? that’s ridiculous. It’s almost as if you want to be the only bloke with PFS on the planet.


#416

Unfortunately an increasing number of chaps are posting on this website with no finasteride related issues (I now count 3 such people) Thee have been more in the past. Of course Moonman has some problems, but if it really was related to 5aR inhibition he would of known, especially as he is a regular contributor to Dr Crislers website. Simple as that.

Then there are people like you, Joe, that have no health problems. Your just a wierdo.


#417

I found this very interesting article about a new epigenetic drug called Entinostat that reverses hormone resistance in breast cancer:
prnewswire.com/news-releases/syndax-pharmaceuticals-announces-issuance-of-eu-patent-for-entinostat-127929723.html

The drug is an oral small molecule inhibotor of clall 1 histone deacetylases. It upregulates the expression of the estrogen receptor in breast cancer cells which have negligible or undetectable levels of ER.

Although this doesn’t apply directly to us, I still find it very exciting. If they could do the same thing and find a way to upregulate the expression of the androgen receptor in prostate cancer cells, maybe that would directly apply to us.


#418

has any body looked at

ghr.nlm.nih.gov/condition/androgen-insensitivity-syndrome

Where can I find information about diagnosis, management, or treatment of androgen insensitivity syndrome?
These resources address the diagnosis or management of androgen insensitivity syndrome and may include treatment providers.

Gene Review: Androgen Insensitivity Syndrome
Gene Tests: Androgen Insensitivity Syndrome
MedlinePlus Encyclopedia: Androgen Insensitivity Syndrome
MedlinePlus Encyclopedia: Intersex
MedlinePlus Encyclopedia: Reifenstein Syndrome


#419

I do not have time to read through all of these posts…

Can someone explain why we would need to demethylate rather than methylate?


#420

Methylation inhibits gene expression. Methylation which is abnormal is the cause for all sorts of serious problems hence the research community’s interest in our problem. That is again if methylation of certain genes or a gene is one of the causes of our problem. As you know, we find out more soon.

Pretty good summary here -
nature.com/scitable/topicpage/the-role-of-methylation-in-gene-expression-1070

There is a program now in Europe - The Human Epigenone Project. They are attempting to map all the epigenetic markers (likely millions) which could help understand how to express some genes and silence others which would be huge. That might be off in the distance a ways and will probably require some serious advances in computing technology to get there any time in the relevent future. No idea if they have gotten to any of the genes that would be of interest to us- AR receptor, vit D receptor, etc.