SRD5A2 gene mutations and 5 alpha reductase function

General Discussion
#1

Recently I stumbled upon the SRD5A2 gene. Some very intresting and important info is in the below mentioned link:

ghr.nlm.nih.gov/gene/SRD5A2

The SRD5A2 gene is a gene that essential makes, oversees the production of, encodes and regulates the 5 alpha reductase type 2 enzyme. people who are born with 5 alpha reductase disorders at birth are found to have mutations in this gene. There are 50 known types of mutations to this gene and its speculated that their could be many more unknown types of mutations to this gene.

My theory is that when we took DHT inhibitets we some how caused a mutation in the SRD5A2 gene. This mutation had made are 5 alpha reductase enzymes that are being produced by this gene to not work properly.

This theory possible explains some of the biggest questions regarding PFS such as why does the returning of DHT in some guys bring on this syndrome and why it seems as if some of us have some 5 alpha reductase function in certain parts of are body but not in other parts.

It’s clear that it is known that there are several different types of mutations to this gene and that depending on what type of mutation it is determines where and what 5 alpha reductase problems that person will have.

It’s also clear that there is such a thing called somatic gene mutations that are gene mutations that occur later in life.

Have we had a somatic gene mutation to are SRD5A2 gene in result of taking DHT inhibitets ?

I’m in the progress of trying to get my SRD5A2 gene tested for possible evidence of mutations.

I will report back with the results

#2

Check it out, info from the website I posted

What is the normal function of the SRD5A2 gene?

The SRD5A2 gene provides instructions for making an enzyme called steroid 5-alpha reductase 2. This enzyme is involved in processing androgens, which are hormones that direct male sexual development. Specifically, the enzyme is responsible for a chemical reaction that converts the hormone testosterone to a more potent androgen, dihydrotestosterone (DHT), in male reproductive tissues.
Testosterone and DHT are essential for the normal development of male sex characteristics. Before birth, testosterone is responsible for the formation of internal male genitalia, including the tubes that collect sperm and carry it out of the testes (the epididymis and vas deferens) and glands that help produce semen (the seminal vesicles). DHT directs the development of the external genitalia, including the penis and scrotum, and the prostate gland. During puberty, these two hormones also play an important role in the development of male secondary sex characteristics such as the growth of facial and body hair, increased muscle mass, and deepening of the voice

#3

Also there is this:

How are changes in the SRD5A2 gene related to health conditions?

5-alpha reductase deficiency - caused by mutations in the SRD5A2 gene
About 50 mutations in the SRD5A2 gene have been identified in people with 5-alpha reductase deficiency. Most of these mutations change single protein building blocks (amino acids) in steroid 5-alpha reductase 2. Some of these genetic changes render the enzyme completely inactive. Other mutations reduce but do not eliminate the enzyme’s function.
As a result of SRD5A2 mutations, the body cannot effectively convert testosterone to DHT in reproductive tissues. A shortage of DHT disrupts the formation of external genitalia before birth. People with 5-alpha reductase deficiency are genetically male, with one X and one Y chromosome in each cell, but they may be born with external genitalia that look predominantly female, or that are not clearly male or clearly female (sometimes called ambiguous genitalia). Other affected infants have external genitalia that appear predominantly male, but they often have an unusually small penis (micropenis) and the urethra opening on the underside of the penis (hypospadias).
During puberty, the testes produce more testosterone. Researchers believe that people with 5-alpha reductase deficiency develop secondary male sex characteristics in response to higher levels of this hormone. Some affected people also retain a small amount of 5-alpha reductase 2 activity, which may produce DHT and contribute to the development of secondary sex characteristics during puberty.

#4

That’s very important!

It says some mutations to the gene make the enzyme completly ineffective and some mutations make the enzyme partially in effective.

That sounds a lot like what we are experiencing a partially ineffective 5 alpha reductase enzyme.

It also explains why some of us have diff symptoms!!!

Because we all have diff types of mutations to this gene.

For example one type of mutation could cause ineffective 5 alpha reductase function in the prostate and other reproductive organs resulting in ED and watery semen but that mutation still allows that person to have effective 5 alpha reductase function on the scalp which is why that guys hair can still fall out but he has limp dick.

While other mutations cause ineffective 5 alpha reductase function in the reproductive of organs and the scalp which is why that guy would have limp dick and his hair would not fall out.

if I become MIA after getting murdered by merk than we know I figured this out!!
LoL!!!

It also explains we have normal DHT readings!!! Because we only have partially ineffective 5 alpha reductase enzymes. For example are prostates not producing DHT may not effect are overall amounts of DHT in are blood all that much but it still gives us ED. It makes so much sense…

#5

if you tell me which is the mutation i can check it on 23andme as they list it in my results.

#6

But how does this cover the people who had taken 1 pill and were fucked up the other day? They were genetically predisposed to mutation?

I’m sure Mew would share some of his insights regarding this. Seems pretty much important to me, nice find.

#7

The Italians are investigating this in their study…

viewtopic.php?f=9&t=10141

#8

Yes. I guess people could just be predisposed to having a genetic mutation to this gene. Just like some people who have not even taken one pill and they are just simply born with a SRD5A2 mutation and suffer from 5 alpha reductase problems at birth

#9

That study is very interesting but where does it mention a possible link to a mutation in the SRD5A2 gene?

#10

Are you saying you have had your SRD5A2 gene tested for evidence of mutation ?

It’s not any type of mutation in particular we would be interested in,

Its any mutation at all found in blood tests to to this gene period

#11

Regulation of Steroid 5-alpha reductase type 2 (Srd5a2) by Sterol Regulatory Element Binding Proteins and Statins

ncbi.nlm.nih.gov/pmc/articles/PMC3124118/

IhatePropecia got cured with nystatin treatment and some have reported improvements from it…

#12

i’m saying 23andme lists this gene.
so i can see if i have some mutation of it.
if you know what mutation you are looking for let me know, it will make my life easier because then i wont need to search it.

#13

What Is 23andme?

I’m not an expert on the SRD5A2 gene and the specific types of gene mutations that researches have found in it. All I know at this timd is that a mutation to this gene can have implications on the 5 alpha reductase type 2 enzyme. I know this because its a known fact that babies born with 5 alphs reductase deffiency disorders have mutations to the SRD5A2 gene. I also know that so far there is 50 known types of mutations to this gene. Its also thought that their are probably unknown mutations yet to be seen to this gene.

Now researches do see certain types of mutations to the SRD5A2 gene in babies that have a micro penis or babies who they can’t tell if they are male or female.

But that’s not really revelent to what I’m saying at this time. What I’m saying right now is that my plan is to do further research into the SRD5A2 gene and learn more about blood tests to test for mutations in this gene.

If you have had any type of blood work releated to the SRD5A2 gene it’s really important that you get to the bottom of what the results where.

What I’m trying to find out is if we had ANY type of mutation to this gene from taking a DHT inhibiter.

We know mutations to this gene is seen in humans. We know this gene has control over the 5 alpha reductase type 2 enzyme. We know we took drugs that attached this enzyme. So it’s not to far fetched that doing this can cause a mutation to this gene

#14

genedx.com/test-catalog/diso … eficiency/

That’s the website that I found that does blood tests that test for mutations in the gene.

But I called them today and they said they only do doctor ordered blood testing

#15

I’m really intrested into knowing what you had done. It sounds like you are familiar with the SRD5A2 gene to have been tested for it.

Or is this just somthing a doctor just added in to your labs ?

I mean if that’s the case than these docs are looking for a lot more than we think

#16

MCI sent me this

[i]One of the other guys txted me this…

My endo has been pursuing the auto immune angle. So he tested me for nuclear antibodies. And I threw out a positive test showing there is some auotimmune issue. Its a broad spectrum test but is indicative of an underlying condition and he’s referring me to a rheumatologist. He said drug induced autoimmune diseases are well documented. Drug induced lupus is one… Any one else have this test?[/i]

We should all get that test, also, Frustrated told me in pm that during the time he had the flu, he had improvement in symptoms.

There is a synthetic 5ar2 enzyme and a 5ar2 antibody which creates an auto immune response which attacks 5ar2 enzymes so that the 5ar2 synthetic enzyme can be tested. It’s possible our 5ar enzymes are mutated and being attacked by our immune system. There is a history of auto immune disorders in my family, how about you guys? Perhaps we should all get this autoimmune disorder test. If this is an autoimmune disease, there are drugs out there that can help us.

Dexamethasone Is an immunosuppressive drug and there have been recoveries from it.

My doctor friend tonight finally heard all that’s wrong with me and looked up the foundation, she now genuinely wants to help. She is going to check the auto immune angle, she was thinking the same thing I was, that the root cause of the enzyme dysfunction could be autoimmune, I will post my results.

#17

The messages are rolling in, Moonman sent me this

[i]"I saw ur post on autoimmunity. The only time Mew has ever “recovered” was while he was sick with a stomach virus.

Dr. John, there is one thing I may be able to contribute to this syndrome, I don’t know if it will be of any insight to you, however – brief, spontaneous resolution 1 year off the drug of post-finasteride symptoms, due to a virus.

After my initial 5 day recovery two weeks after quitting Finasteride (flood of DHT returned, felt horny/alive/full erections etc… followed by subsequent crash in T levels, and all hell breaking loose from that point on), I experienced a brief, 2-day semi-recovery approximately one year off the drug when I had a form of Norovirus/gastroenteritis.

During those 2 days, starting at 4am with a massive stomach ache, I was persistently puking up bile and having diarrhea every 15-30 minutes for about 7 hours straight, combined with chills and a minor fever, to the point of dehydration and having to go to the hospital for rehydration with saline.

Upon my return home later that day, I noticed my testicles had blown up to their former pre-Finasteride size (full, not wrinkly/empty), and my penis was no longer retreating, not veiny/skinny/narrow, but engorged with blood when flaccid as I used to remember it before Finasteride. I also began to feel a bit of a surge in libido returning. During this time I even looked at some porn and found I was able to get decently turned on and obtain an erection without issue.

However, over the next 1.5 days, as the virus worked its way through my system and left my body, so did this period of brief semi-recovery. I can only speculate as to what caused this, but to me it most certainly points to a hormonal issue in that the virus either interfered with my HTPA and caused a surge in LH/FSH, or the fact that I was puking up bile constantly and in effect was stimulating my liver to the point of overactivity.

Trying to find answers, I did some research and came across this:
jcem.endojournals.org/cgi/reprint/76/4/977.pdf

Since the liver plays a major part in steroid metabolism, especially 5-AR reduced metabolites, and since Finasteride is metabolized extensively in the liver, perhaps there is some sort of connection there.

Anyway, just thought I’d share that with you. I was amazed that after one year of Finasteride side effects, my body spontaneously recovered to a point on its own – due to a virus. This tells me that it is in fact possible to recover from the effects of this drug, no matter how long one has been off".[/i]

#18

I now hear reports similar to mine, when my sleep is low, my symptoms improve, my immune system is weak, when I am overtired I start getting more horny. Moonman said the same thing, anyone else?

#19

Me.
When i sleep worse i have more sexual ddesire.
Its like i cant have both.

The difference is if i sleep properly, im not as horny but i can get there easily if i need too…

#20

We should all get this nuclear antibody test, there are 5ar antibodies, it’s possible this drug triggered an autoimmune response in us. Anyone else have improvements when sick or tired? My dad has rheumatoid arthritis and is on embrel - an immunosuppressive biologic, autoimmune disorders run in my family. There is dexamethasone and the recoveries that have come from it, it is immunosuppressive. Perhaps the reason people recover sometimes is due to their immune system attacking the mutated 5ar enzymes (or the enzymes in general), at some point the defects are destroyed after a period of time and corrected. Has anyone explored this disorder from an autoimmune angle? I can’t go on with this condition, I must solve it, whatever protocols I use are adapted to, no matter how advanced they get, I have even added amino acid blend intramuscular injections to help muscles, and it’s helping. It seems though as I am fighting something that is alive, something that adapts to counter my protocols. All that works is a modulating protocol (something that changes constantly) To counter adaptation. I cannot go on like this long term, the times I responded and spontaneously recovered, my immune system could have been weak, or the culprit was attacked and suppressed. I have posted here as I feel this angle is so important that I want maximum exposure and information. If what we are dealing with is autoimmune, it’s not something that is that out of the question to treat. In those who have not responded to immuno suppressive drugs, their hormones may have been too low. Those on hormones or with ideal hormones would essentially recover with immunosuppressive drugs if this were true. Has anyone else had similar stories of improving while sick or sleepless?

MCI said his dad has an auto immune disorder, my dad does too, it’s hereditary, does anyone else here have autoimmune disorders in their families? This drug could have tripped a gene and induced an autoimmune disorder.

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