XMRV and progesterone

[JanisB]

Hi All,
I just read in Cheney's newsletter that progesterone 'activates' XMRV.

Well since I'm not going to pay $50 to read the whole thing -- the exploitation of very sick ME/CFS patients by a few famous doctors is soooo annoying -- I wonder if anyone knows what this is all about.

Here's the part I get for free:

The immunosuppression of ERVs and XMRV Is XMRV actually chronic Lyme disease?

Below is an interesting link to a thorough discussion on gammaretroviruses and the related human endogenous retroviruses ERVs of which there are 2,000 ERV genes located on a single human chromosome. There are thousands of ERVs spread across the entire human DNA grouped into 24 families. XMRV has 95% homology with human ERVs. What is very interesting about ERVs and likely true for XMRV is that they are TH1 immunosuppressive which is believed to be critical in the ability to get pregnant as the mother needs to be Th1 immunosuppressed to avoid rejection of the implanted fetus. The hormones of pregnancy and especially progesterone are in part responsible for activating env proteins of ERVs which apparently are largely responsible for this immunosuppression. It is likely that progesterone activates XMRV env protein and may explain why we see women with more CFS at 4 to 1 over men and the apparent vulnerability of adolescent girls to CFS onset and the relative reduction of the point prevalence of CFS in the elderly and in children compared to the young to middle ages. I have also observed a reduction in severity of CFS symptoms in post-menopausal women though perhaps modulated by their use of HRT. The related hormones to progesterone are pregnenolone and cortisol. I have seen both devastate a handful of CFS cases.

Does progesterone activate other viruses? Herpes viruses tend to like high levels of arginine, but I don't think that activates them. And stress can raise cortisol levels to an immunosuppressive level, allowing latent viruses to become reactivated.

I take progesterone to keep my estradiol progesterone ratio is some kind of balance. Does anyone advise reducing or eliminating progesterone supplements? Where would that leave women who are estrogen dominant?

His post also said that pregnenelone and cortisol had similar effects. But I found taking cortisol greatly reduced my orthostatic intolerance symptoms when I relapsed in the fall of 2007. If viral activation caused the relapse, then theoretically, taking cortisol should have made me even worse.

JanisB

 

[tahoma]

Interesting. When I underwent hormone testing and proceeded to use bioidentical RX progesterone cream, I experienced the most horrific flare of my illness I can ever recall. It took me three months to come out of that hellhole. I waited another year and tried it again... same result. I've often wondered about this severe reaction to progesterone....

Tahoma

 

[fds66]

I have wondered about the role of hormones because when I was pregnant my symptoms were so much better. The first few monthes I was tired and sick like everyone seems to be but after the first 14 weeks or so I started to feel better. I felt better than I had done for years and had more energy even while heavily pregnant. This continued for a while after I gave birth and while breastfeeding. Unfortunately this didn't last forever but it has intrigued me how much better I felt then. It was as if a lot of the ill feeling had lifted - hard to explain in any other way than that.

Just as background I had ME for 6 years before I was pregnant and my son is now 12 and I still have ME and apart from that period of time while pregnant I've had no improvement at all. If anything the ME is worse now than it has ever been.

 

[Jenny]

Hi fds66

Your experience seems to go against Cheney's hypothesis, as progesterone rises as pregnancy progresses.

I first came down with ME when 4 months pregnant with my second child, so it's possible that immunosuppression and/or a rise in progesterone were implicated. After 3 months in bed I slowly improved and was fine for the birth, then got worse again some months later.

For anyone wondering about breast feeding, I breast fed my daughter for a year. She is 27 now and (touch wood) has always been in good health. My son too was breast fed - he is 29 now and healthy.

Now, post-menopause, I'm as bad if not worse than I ever have been. So that doesn't tie in with the progesterone hypo.

Jenny

 

[fds66]

The story I've heard is that it is unpredictable how people react to pregnancy - some people improve while pregnant, some get worse and some stay the same.

 

[perovyscus]

It's a very interesting theory indeed.

In prolonged periods of stress (infection, childbirth, life stress) the body replaces cortisol with DHEA and progesterone to reduce your future load on the organ systems. It lowers your exercise capacity. It also has to have a genetic component, since not all survivors of concentration camps received CFS.

So, there's your stress event

Normal cortisol is maintained via an excessive release of norepinephrine, which the body perceives as stress.

Progesterone is competitive with the mineralocorticoid receptor, and high progesterone may explain the orthostatic intolerance CFS patients face. The main product for blood pressure elevation isn't there to elevated blood pressure!

Progesterone is essentially air in males. It isn't immunostimulatory like DHEA, and doesn't suppress Th2 immunity like glucocorticoids would. It just takes up space, and when stress hits, there's nothing to support exertion.

Progesterone is absurdly pro-viral 24/7. It prevents the antiviral molecules TNF-a, IFN-y, and other major players. If it is so anti-inflammatory, though, how come muscles ache? This may be due to progesterone taking the place of the strongest anti-inflammatory, cortisol, during any period of exertion.

I can explain how excess progesterone would impact intelligence positively and still retain drive in people otherwise demolished by illness. It probably has some mild MAOI effects (MAOI). Patients in a trial of progesterone noticed significant anti-depressant capabilities. The fog itself may also be related to viral infection and the associated cytokine release within the blood brain barrier. There are limited testing methods to prove this case.

So where does XMRV fit in? Same place every prospective virus would. It's replicating throughout the system so fast due to:

1) Low levels of antiviral cytokines
2) B-cells that are harboring the virus are growing faster than the NKCs

So where do bacterial illnesses fit in?

I don't know.

If the data on CFS patients is true (Th2 dominance)... To be maddeningly simplistic (sort of like John Madden), your body would tend to be antibacterial. Now, if a patient has a repeat Lyme diagnosis, disregard. I can't really stress this enough, though. Most antibiotics have "molecular biologically explained mechanisms of action" but clinically most are simply "anti-inflammatories."
It explains why colds, rhinoviruses, respond better to antibiotics than placebo. It explains why patients feel better when they take an antibiotic for a cold, and why moron doctors keep prescribing them. That was a tangent.

A fungus is more likely to be the culprit of CFS than a bacterium. Book it.

If progesterone improves the quality of a patient's life, I'm not surprised. It has a lot of psychologically enhancing capabilities.

The research on progesterone inhibition is about as diverse as XMRV inhibitors, although one famous drug exists for progesterone.

The research for XMRV may take years, and I hope it pans out with data that is accurate and replicated. Just something to think about how complex the problem is. The lone gunman is a simple theory, but a good conspiracy often has basis in unanswered questions.

And no, that was not the article from Cheney.

 

[Lynn]

Progesterone

I believe that Judy Mikovitz metioned the relationship of progesterone in the Nevada News interview. I noticed it because I have had severe flares from progesterone.

About 6 years ago, I had a hormone test that showed low levels of progesterone and my Dr. first prescribed progesterone capsules and when I couldn't tolerate the capsules, I tried the cream. I tried it for about 3 weeks but felt like I was having a major reversal in my illness.

Recently, since I am heading into menopause my Dr. prescribed a very small dose of progesterone, saying something about avoiding endometriosis. I tried it for a few days on two separate occasions and the results were unbearable. Major pain, fatigue and toxicity. My doctor could not believe that such a small dose could cause such symptoms.

I am very interested in talking to him about the XMRV and progesterone. I see him later this month.

Lynn

 

[usedtobeperkytina]

Things

Things that affect my symptoms:

1) pacing- taking rests during the day (helps)
2) period- a few days before and three days during, count on it (hurts) This may be due to drop in other hormones, allowing the progesterone to run the show.
3) lack of sleep- following day feel better. Day after, feel much worse. (helps and hurts)
4) no sugar and probiotics (helps with GI problems)
5) changing activities- computer work for an hour, house cleaning for an hour, rest and hour, don't do two hours straight of mental and don't do two hours of physical
6) cut out stress (helps)

All the other stuff I do to try to help, including meds and supplements, I can't tell if helps or not.

Tina

 

[Elisa]

Q: Is progesterone an XMRV entry inhibitor?

Hi,

There is a lot of talk about hormones and XMRV. In the recent Cheney video, WPI's Dr. Mikovits stresses "hormone balance" and avoidance of excess androgens, estrogens and cortisol.

In addition, there is information that XMRV uses the progesterone receptor on the cell to gain entry. So is it possible that low progesterone levels - common in estrogen-dominant women/society - perpetuate the illness.

Here is a quote from Dr. Luckett's blog:

"I think progesterone actually has a protective effect, by acting as a cell entry inhibitor. XMRV competes with the membrane bound progesterone receptor, as opposed to the classic nuclear binding cytoplasmic receptor."

[/INDENT]

and

"Observations reveal that high rates of estrogen, or high rates of testosterone in the absence of progesterone tend to favor the growth of XMRV - progesterone inhibits the formation of DHT."

Here's the link:

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

Also could this be the reason why so many with this illness - go into remission when pregnant - or at least feel better/improve?

For those interested, be sure to read the above blog comments too.

God Bless,

Elisabeth

 

[julius]

Interesting thought.

Where did you see that XMRV binds to the progesterone receptor?

 

[Elisa]

I read it in the first paragraph of the blog I linked to above...

I am thinking, theoretically, that if the receptor is a progesterone receptor then keeping it occupiedl with bioidentical progesterone, if necessary, would inhibit XMRV cell entry or at least slow it down.

Most CFS females are estrogen dominant (many environmental estrogens and mimic-ers) and many become that way more over time. The only time they are clearly progesterone dominant is during pregnancy. This is also a time many with CFS feel good/great. Although, progesterone is thought to be immnosuppressive in general (in pregnancy high levels prevent mother's immune system from attacking child) in this case it may be useful in locking out, so to speak, a greater immune/cell threat, XMRV.

Elisabeth

 

[Jenny]

I think I've said this on another thread, but I first became ill with ME when I was 3 months pregnant 28 years ago with my second child.

After a long period of mainly good health I began getting worse in 2004 when on a form of HRT with a high amount of progesterone.

I thought some took the view that XMRV is turned on by progesterone.

Jenny

 

[Dreambirdie]

I've had mostly good results with progesterone. Only when I did TOO HIGH a dose, did I get into some problems with agitation.
I think that with hormones, it is A VERY INDIVIDUAL THING. You have to check your levels regularly and see what your body needs.

Also, there is this to consider: "Progesterone May Improve Outcomes From Brain Injury"
http://www.lef.org/magazine/mag2009...May-Improve-Outcomes-From-Brain-Injury_01.htm

 

[spindrift]

I am not sure about the science on this, but progesterone definitely makes me worse.
It is one of my worse triggers and just as bad as over doing physical activity.

 

[rmendoza]

Progesterone is NOT the receptor.

Hello All,
I feel I must correct something on this thread. The receptor for the XMRV virus is XPR1 which is most likely a g-protein coupled receptor. The progesterone link with XMRV has to deal with the replication step of the virus. The promoters of XMRV, called Long Terminal Repeats (LTR's), which are located at either end of the XMRV genome contain sequences that are responsive to steroids like progesterone and dexamethasone. Add these compounds to the cells that have the virus increases the amount of viral particles made and released by the cell.

I hope this helps clarify the information for you.

 

[spindrift]

Hello All,
I feel I must correct something on this thread. The receptor for the XMRV virus is XPR1 which is most likely a g-protein coupled receptor. The progesterone link with XMRV has to deal with the replication step of the virus. The promoters of XMRV, called Long Terminal Repeats (LTR's), which are located at either end of the XMRV genome contain sequences that are responsive to steroids like progesterone and dexamethasone. Add these compounds to the cells that have the virus increases the amount of viral particles made and released by the cell.

I hope this helps clarify the information for you.

Welcome to the forums!
Thanks for that info.

I also get worse taking steroids for inflammation. Do you know if there could be the same connection to other steroids,
such as in prednisone?

 

[Countrygirl]

Interesting thought.

Where did you see that XMRV binds to the progesterone receptor?

According to one of the comments at the end, this statement is erroneous.

'There is no evidence that Xpr1, the cell entry receptor for XMRV, is a progesterone receptor. This incorrect conclusion stems from the unfortunate use of the term Xpr-1 as an abbreviation for the Xenopus Progesterone Receptor-1, which has no relationship to the XMRV receptor Xpr1.'

 

[rmendoza]

Welcome to the forums!
Thanks for that info.

I also get worse taking steroids for inflammation. Do you know if there could be the same connection to other steroids,
such as in prednisone?

Possible that prednisone can increase viral replication. However, prednisone is immunosupressive so seperating out the induction of viral replication by prednisone as oppesed to immunesupressive effects would be difficult.

 

[julius]

According to one of the comments at the end, this statement is erroneous.

'There is no evidence that Xpr1, the cell entry receptor for XMRV, is a progesterone receptor. This incorrect conclusion stems from the unfortunate use of the term Xpr-1 as an abbreviation for the Xenopus Progesterone Receptor-1, which has no relationship to the XMRV receptor Xpr1.'

Thanks,

It didn't sound right to me, but rmendoza's explanation cleared it up for me.

XPR-1 having two meanings clears it up even more.

 

[spindrift]

Thank you Countrygirl and rmendoza for your explanations.

Possible that prednisone can increase viral replication. However, prednisone is immunosupressive so seperating out the induction of viral replication by prednisone as oppesed to immunesupressive effects would be difficult.

Now I am wondering if the replication of XMRV has to be induced by something. Meaning does it just 'sit there' and not
replicate if nothing is inducing replication or is it replicating all the time and a malfunctioning immune system just lets
it replicate better?


Wish I had taken more biology classes.