Androgen stimulates transcription and replication of XMRV

[Francelle]

I read this a short while ago and have been wondering if it is NOT a good idea to take supplemental DHEA even though my androgen levels are undetectable??? Assuming of course that I am positive for XMRV!

 

[Gerwyn]

ETA - Okay I just realized the abstract to this HAD been posted (of course) here:

http://www.forums.aboutmecfs.org/sh...of-XMRV&highlight=androgen+xmrv+transcription

...and if there is a way to delete threads I forgot how. If any mod/admin reads this, could you please delete this thread?
----------------------------------------------------------------------


Androgen Stimulates Transcription and Replication of Xenotropic Murine Leukemia Virus-Related Virus

Beihua Dong and Robert H. Silverman*
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195
Received 20 August 2009/Accepted 4 November 2009

Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus originally identified in a subset of prostate cancer patients. Because androgens stimulate prostate tumors and some retroviruses, we investigated the effects of dihydrotestosterone (DHT) on XMRV transcription and replication. Transcription from the XMRV U3 region was stimulated up to 2-fold by DHT, but only in cells containing a functional androgen receptor. Mutations in the glucocorticoid response element (GRE) of XMRV impaired basal transcription and androgen responsiveness. Furthermore, DHT stimulated XMRV replication 3-fold, whereas androgen inhibitors (casodex and flutamide) suppressed viral growth up to 3-fold. Findings suggest that integration of the XMRV long terminal repeat (LTR) into host DNA could impart androgen stimulation on cellular genes.

XPR-1 is an androgenic receptor.This is how progesterone exerts its hormone effects

 

[DysautonomiaXMRV]

If I may, off subject, but not off topic a few questions.

1) If adolescent & mature females have more progesterone than males, could this be one reason why XMRV is highly 'enabled' in women (in comparison to men) thus creating a state of neuro immune disease - CFS/ME - which is predominantly a females condition?

2) Can men who are XMRV+ and who have signs of neuro immune disease (CFS/ME) have their progesterone measured to compare their progesterone levels with healthy XMRV- controls?

3) Why are people with CFS/ME reporting lower than normal cortisol levels, and/or abnormal ACTH stimulation tests? Where does the cortisol go? Does XMRV 'use' it? Or does XMRV impair adrenal gland function through organ (adrenal gland) infection?

4) What are the base line levels of DHEA and DHEA-S in XMRV+ males and females, compared to healthy controls?

 

[girlinthesnow]

I took a DHEA supplement two years ago for about 5 months on the advice of a nutritional therapist based on the results of a adrenal saliva test which showed cortisol low, DHEA-s erratic and low production. This coincided with a huge increase in energy and a large improvement in pain and then was followed by a huge crash from which I have not recovered. The first signs of the crash were intense neuropathic pain of electric shocks, blacking out episodes and an intense pain in my abdomen.

An illustration of the problem of treating with a little knowledge.

 

[*GG*]

I have been taking 25 mg of DHEA for the last year and have recently increased it to 50mg because my Cortisol is still low!

I have also increased my Cortef from 10mg to 20mg after 3 weeks of not noticeable difference in my conditon at 10mg.

This is all under advisement from my doctor.

 

[leaves]

Heh I had the same: false diagnosis of pcos. Don't have the hair though. Very low estrogen, progesterone and everything else, and xmrv+
weird question; but does xmrv eat your hormones? Or does your body downregulate it for protection?

I found a sort of "androgen for dummies" and women type article here

http://www.infertilityphysician.com/androgen/intro.html

Years ago when I was being examined for infertility I was told that I was PCOS like and that my ovaries showed signs of PCOS. However, there was something that didn't add up in my blood-work that stopped the diagnosis of PCOS being made. I'm going to have to dig out those very old test results and see if I can make sense of it.

Certainly I fit the pattern described in that article for too much androgen in women (hair, body shape etc).

I've got low cortisol, low cholesterol.

XMRV+

 

[acer2000]

If I may, off subject, but not off topic a few questions.

1) If adolescent & mature females have more progesterone than males, could this be one reason why XMRV is highly 'enabled' in women (in comparison to men) thus creating a state of neuro immune disease - CFS/ME - which is predominantly a females condition?

2) Can men who are XMRV+ and who have signs of neuro immune disease (CFS/ME) have their progesterone measured to compare their progesterone levels with healthy XMRV- controls?

3) Why are people with CFS/ME reporting lower than normal cortisol levels, and/or abnormal ACTH stimulation tests? Where does the cortisol go? Does XMRV 'use' it? Or does XMRV impair adrenal gland function through organ (adrenal gland) infection?

4) What are the base line levels of DHEA and DHEA-S in XMRV+ males and females, compared to healthy controls?

I'm no expert, but I doubt that absolute androgen levels can explain why females have a higher incidence of CFS than males. For males, testosterone is the primary Androgen, and males have much higher levels throughout their lives than females do. Perhaps its the cyclical change in progesterone levels in females that provokes XMRV replication, whereas in males testosterone levels are mostly static? Or perhaps the relationship is more specific than "androgen stimulates XMRV" - perhaps its a specific type of Androgen, or its dependent on receptor expression which is different between the sexes. Like everything with this disease, hormone relationship to XMRV is likely way more complicated than "we have more or less of this or that androgen" - however. :-(

 

[Otis]

I think this is an interesting area for study. As I recall Dr. Bell says the pediatric ratio is 1:1 which would appear to mean that puberty is the event that tips the scales drastically to the female side.

I'm a gradual onset male who got servery worse upon starting testosterone supplementation in hopes of giving me energy. It seemed reasonable at the time. I'm pretty sure that was the trigger to my decline and not anything else.

Unfortunately stopping the testosterone hasn't helped which if it caused XMRV to transcribe and replicate. I've yet to be tested for XMRV.

 

[awol]

I found this:

http://cfidsresearch.blogspot.com/2009/11/modus-operandi-of-xmrv-pt1.html

The implication seems to be that XMRV MIMICS progesterone and uses this as a way to hide from the immune system. This could help explain why, according to the author, ME/CFS is more prevalent in women.

Analysis?

 

[Rrrr]

there is this med that lowers androgens. it is called spironolactone. http://en.wikipedia.org/wiki/Spironolactone

i took it for years to lessen my body hair that i get from polycystic ovaries. a few years ago i stopped taking it on a whim. and then i got much sicker. i did not put one and one together until i heard judy mikovits say in november 2009 that cortisol, estrogen and androgens make xmrv reproduce.

so last month i asked judy if, in theory, spironolactone would help lessen xmrv due to its anti-androgen effects. she said yes, in theory, and she wants to test it in the lab. (i doubt she has, given all the politics happening. but i'll ask her again.)

so i went back on spironolactone a few weeks ago, at a tiny dose, and started to do somewhat better. and my brain started working better too. less brain fog.

then just 6 days ago i doubled the dose and within 2 days felt a lot better. a lot. so it is only 4 days of doing better. but it is curious how linked it is to the spironolactone.

does anyone want to experiment with this and get a prescription of spironolactone and try it yrself? i'd love to hear if anyone else gets help from this med. it is easy to take. no side effects in me (over the years) except a bit more liquidy period, less clotty (eeeeeeewww! too much information!!!!!)

i'll now repost some earlier posted info, as it relates:

Androgen Stimulates Transcription and Replication of Xenotropic Murine Leukemia Virus-Related Virus

Beihua Dong and Robert H. Silverman*
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195
Received 20 August 2009/Accepted 4 November 2009

Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus originally identified in a subset of prostate cancer patients. Because androgens stimulate prostate tumors and some retroviruses, we investigated the effects of dihydrotestosterone (DHT) on XMRV transcription and replication. Transcription from the XMRV U3 region was stimulated up to 2-fold by DHT, but only in cells containing a functional androgen receptor. Mutations in the glucocorticoid response element (GRE) of XMRV impaired basal transcription and androgen responsiveness. Furthermore, DHT stimulated XMRV replication 3-fold, whereas androgen inhibitors (casodex and flutamide) suppressed viral growth up to 3-fold. Findings suggest that integration of the XMRV long terminal repeat (LTR) into host DNA could impart androgen stimulation on cellular genes.

Gerwyn added this comment earlier, too, in relation to this above study: "XPR-1 is an androgenic receptor.This is how progesterone exerts its hormone effects"

 

[Mya Symons]

I read somewhere that XMRV prefers progesterone to replicate and that is why CFIDS and FMS affects more women than men. I am going to get a progesterone IUD to control heavy bleeding and pain. I hope I am not making the wrong decision. My doctor said if the side effects are horible, she will remove it. Hopefully, she will remember she said that.

 

[OverTheHills]

Hmm, Mya your medical decisions are entirely yours to make but perhaps it would be useful to share my experience.

I tried the IUD to combat endometriosis pain (vomiting, morphine injections etc) and heavy bleeding. I had poor results with a progesterone IUD - same side effects as the pill, made me feel really tired and sluggish after a couple of weeks (and this was pre-ME/CFS). I had it taken out.

I have had much more success with a combo of diet change, supplements and mefanamic acid. I'm normally more inclined toward conventional medicine so I was surprised. PM me if your interested in details/ a boook reference.

OTH

I am going to get a progesterone IUD to control heavy bleeding and pain. I hope I am not making the wrong decision. My doctor said if the side effects are horible, she will remove it. Hopefully, she will remember she said that.

 

[Cloud]

"Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus originally identified in a subset of prostate cancer patients. Because androgens stimulate prostate tumors and some retroviruses, we investigated the effects of dihydrotestosterone (DHT) on XMRV transcription and replication. Transcription from the XMRV U3 region was stimulated up to 2-fold by DHT, but only in cells containing a functional androgen receptor. Mutations in the glucocorticoid response element (GRE) of XMRV impaired basal transcription and androgen responsiveness. Furthermore, DHT stimulated XMRV replication 3-fold, whereas androgen inhibitors (casodex and flutamide) suppressed viral growth up to 3-fold. Findings suggest that integration of the XMRV long terminal repeat (LTR) into host DNA could impart androgen stimulation on cellular genes".

I understand this to mean that stimulated xmrv replication secondary to the presence androgen hormones is hardly significant since it's only affecting the virus in limited organ/tissue area's. I would have to get my physio books out to get a better idea. Waiting for more research to unfold sounds best. I can't see any difference in how I feel after 4 months of Finasteride, which blocks the DHT conversion. But then, I fluctuate up and down so much will all the Tx I have going on, it would be very difficult to tell.

I do tend to believe that stress hormones, particularly Cortisol (which has widespread receptors), may stimulate xmrv replication. I have always felt there is more to the Post exertional relapse than just Cytokine Storm. I have labs showing a spike in increased viral load counts with particular pathogens, when in a crash. Another reason is that my worst and longest crashes have come after taking meds that directly or indirectly stimulate Cortisol production. Actually, anything that encourages our systems to function better is going to increase Cortisol production. Interesting that my 17 year experience with attempting to get well is that no matter what it is that makes my system function better, it always results in a crash.

 

[Rrrr]

"Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus originally identified in a subset of prostate cancer patients. Because androgens stimulate prostate tumors and some retroviruses, we investigated the effects of dihydrotestosterone (DHT) on XMRV transcription and replication. Transcription from the XMRV U3 region was stimulated up to 2-fold by DHT, but only in cells containing a functional androgen receptor. Mutations in the glucocorticoid response element (GRE) of XMRV impaired basal transcription and androgen responsiveness. Furthermore, DHT stimulated XMRV replication 3-fold, whereas androgen inhibitors (casodex and flutamide) suppressed viral growth up to 3-fold. Findings suggest that integration of the XMRV long terminal repeat (LTR) into host DNA could impart androgen stimulation on cellular genes".

I understand this to mean that stimulated xmrv replication secondary to the presence androgen hormones is hardly significant since it's only affecting the virus in limited organ/tissue area's. I would have to get my physio books out to get a better idea. Waiting for more research to unfold sounds best. I can't see any difference in how I feel after 4 months of Finasteride, which blocks the DHT conversion. But then, I fluctuate up and down so much will all the Tx I have going on, it would be very difficult to tell.

I do tend to believe that stress hormones, particularly Cortisol (which has widespread receptors), may stimulate xmrv replication. I have always felt there is more to the Post exertional relapse than just Cytokine Storm. I have labs showing a spike in increased viral load counts with particular pathogens, when in a crash. Another reason is that my worst and longest crashes have come after taking meds that directly or indirectly stimulate Cortisol production. Actually, anything that encourages our systems to function better is going to increase Cortisol production. Interesting that my 17 year experience with attempting to get well is that no matter what it is that makes my system function better, it always results in a crash.

cloud: are you up for trying to explain to me what your 2nd paragraph means? i can't grasp the 1st paragraph at all. and i can't even grasp the 2nd one, where you try to explain the first one. (i especially don't get the first line of that 2nd paragraph)

is the med you have been taking for 4 months the same, more or less, as the med i'm taking: spironolactone? that is, do BOTH meds block the DHT conversion of which you speak?

 

[Cloud]

Rrr...I too thought it sounded a little tongue tied, lol. Sometimes my brain fog manifests as nonsensical chatter. And yes, the second paragraph was my response to the first (quoted) one.

The first paragraph (quoted) says to me that androgen hormones can cause a 2 fold increase in xmrv replication.....Yikes! But then it also says that only appears to happen in cells with androgen specific receptors. Well, that's limited areas in the body which to me diminishes this anxiety over these hormones causing any significant increased xmrv viral load. I was just trying to say that it appears to me that androgen hormones stimulating xmrv replication, is no big deal because it may be minimal. Of course, I could be wrong.

As far as the meds.....not the same at all. Spironolactone is a diuretic and Finasteride is primarily for men with BPH. Finasteride definitely inhibits the DHT conversion and that's it's target in men. It doesn't sound right to me that Spironolactone would inhibit DHT conversion because it's target is the kidneys. I would have to research that. I think researching hormone modulating diets is a good idea too.

 

[Rrrr]

all i know is that spironolactone seems to be helping me a lot. i don't get it. maybe it is another factor. there are always 100 variables in my life that could be making me do better or worse at any given time. but this upswing of energy and brain power seems to corrolate with taking spironolactone.

does anyone else want to give this a try? let me know!

rrrr

 

[Tembo]

all i know is that spironolactone seems to be helping me a lot. i don't get it. maybe it is another factor. there are always 100 variables in my life that could be making me do better or worse at any given time. but this upswing of energy and brain power seems to corrolate with taking spironolactone.

does anyone else want to give this a try? let me know!

rrrr

This is facinating Rrrr - will you keep us posted on if it continues to make you feel better? I might ask my doc about it.
I have a question though - im low in progesterone and take hormone replacement progesterone cream 18days out of each month - does this mean it could be worsening my xmrv? (if i have it)

 

[Rrrr]

this is a great question, tembo, and yet i'm clueless on the answer. it seems that many women would want to know the answer to this one! can you email judy mikovits and ask her?

 

[Tembo]

this is a great question, tembo, and yet i'm clueless on the answer. it seems that many women would want to know the answer to this one! can you email judy mikovits and ask her?

ah now theres a good idea I might do that:Retro smile:Ill let you know if she replies.

 

[grant107]

Did Judy Mikovits say that estrogen activates xmrv? I thought it was only androgen. Since I have had my ovaries removed my body cannot make androgen, so it could be the spironolactone helps for another reason. I take a small amount of estradiol to keep from having hot flashes. When I have been of it my cfs did not improve.