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Study: DHT Stimulates XMRV by 3-fold

dannybex

Senior Member
Messages
3,561
Location
Seattle
"Furthermore, DHT stimulated XMRV replication by 3-fold, whereas androgen inhibitors (casodex and flutamide) suppressed viral growth up to 3-fold. Findings suggest that integration of the XMRV LTR into host DNA could impart androgen stimulation on cellular genes."

http://www.ncbi.nlm.nih.gov/pubmed/19906923

Makes me wonder if a natural alternative -- saw palmetto (Serenoa repens) might also indirectly inhibit XMRV, because of it's effect on DHT?

http://www3.interscience.wiley.com/journal/76945/abstract?CRETRY=1&SRETRY=0

???
 

Dan

Messages
26
Location
Perth Australia/NC USA
"Findings suggest that integration of the XMRV LTR into host DNA could impart androgen stimulation on cellular genes."

Does this mean that androgen production could increase in the presence of the virus?
 
C

cold_taste_of_tears

Guest
Don't androgen's increase significantly during puberty?
(A frequent time in history when teens develops this illness).
 

Sing

Senior Member
Messages
1,782
Location
New England
Would someone please tell me what DHT is and also what XMRV LTR is?

I want to understand these dynamics between our various hormones and XMRV but don't know what all the bits are.

Thanks!

Cecelia
 
D

duendeni

Guest
Point of interest

I remember reading that acne is very common amongst ME sufferers. I often have break-outs during periods of relapse/after exertion. Acne can be caused by excessive levels of the male sex hormone androgen, which can cause enlargement of the sebaceous glands.
 
D

duendeni

Guest
Would someone please tell me what DHT is and also what XMRV LTR is?

I want to understand these dynamics between our various hormones and XMRV but don't know what all the bits are.

Thanks!

Cecelia


DHT is Dihydrotestosterone, a metabolite of testosterone. Actually now I come to think of it, when I was diagnosed intially I had amenorrea and clinically high levels of testosterone for girl of 16.
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
Would someone please tell me what DHT is and also what XMRV LTR is?

I want to understand these dynamics between our various hormones and XMRV but don't know what all the bits are.

Thanks!

Cecelia

from wikipedia:

"Dihydrotestosterone (DHT) ... is a biologically active metabolite of the hormone testosterone, formed primarily in the prostate gland, testes, hair follicles, and adrenal glands by the enzyme 5α-reductase by means of reducing the 4,5 double-bond. Dihydrotestosterone belongs to the class of compounds called androgens, also commonly called androgenic hormones or testoids. Androgens are part of the biology of gender by stimulating and controlling the development and maintenance of masculine characteristics. DHT is 3 times more potent than testosterone; testosterone is 5-10 times more potent than adrenal androgens.[1]

While DHT is best known for its roles in causing male pattern hair loss and prostate problems, it is crucial to virilization and is necessary to mitigate estrogen's effects in men.

Not sure how this applies to women...

???
 

joyscobby

Senior Member
Messages
156
some women, I like myself have been given it to treat gyne problems, endometriosis. there was also something about estrogen and pegosterone having a role. I think this has been discussed elsewhere but not sure where maybe some one could find it.

I remember vaguely mentioning about bauld men but to tired just now to look it up and figure out how to link.
 

Advocate

Senior Member
Messages
529
Location
U.S.A.
Would someone please tell me what DHT is and also what XMRV LTR is?
Cecelia

I think LTRs are promotor sequences.

Wikipedia: Some oncogenic retroviruses i.e. cancer-causing viruses with RNA genomes, insert their genome into the host cell and use reverse transcriptase to make DNA. This DNA is then incorporated into the cell DNA along with powerful promoter sequences (LTRs) that promote transcription of the viral DNA to reproduce more virus. However, sometimes the viral DNA incorporates a section of the host DNA which contains genes for growth promotion. These growth genes, sometimes called proto-oncogenes in their normal state, become oncogenic once incorporated into the viral DNA because of the increased transcription caused by the viral (LTRs). This causes increased growth of the infected cell, leading to cellular proliferation and the formation of tumors. Numerous oncogenes have been discovered in the genomes of transforming retroviruses.

Coffin mentioned LTRs when he spoke to CFSAC.

From the Coffin transcript at:
http://aboutmecfs.org/Rsrch/XMRVCoffin.aspx

As I said these are not directly pathogenic in mice, but if you isolate some pathogenic cancer causing viruses from mice, they will have a sequence, a very important sequence which is the Long Terminal Repeat which contains all of the signals for gene activation for directing transcription of this and for turning on oncogenes which causes the cancer and that LTR comes from the xenotropic virus and its very similar (not quite identical few little differences) but its very similar in sequence to the virus in XMRV.
 
D

duendeni

Guest
All women should have testosterone to some degree

Wikipedia:

On average, an adult human male body produces about forty to sixty times more testosterone than an adult human female body, but females are, from a behavioral perspective (rather than from an anatomical or biological perspective), more sensitive to the hormone.[2] However, the overall ranges for male and female are very wide, such that the ranges actually overlap at the low end and high end respectively.
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
thanks...

Yes...I don't think we should be afraid of normal hormone levels, but with regards to DHT mentioned in this study, it can be very elevated in men, so that's why I asked about saw palmetto. Perhaps that would indirectly inhibit XMRV...?
 

CBS

Senior Member
Messages
1,522
I came across the androgen research about a week ago. I have been diagnosed as having a number of endocrine issues including very low DHEA (a testosterone precursor) and low testosterone that drops even further during periods when I am not doing well. My endocrinologist has repeatedly prescribed testosterone replacement. It has done nothing. If anything it makes me feel worse. My endo finally agreed that treating the low testosterone is a personal choice. I've stopped. When I saw this I wondered about a connection.
 

August59

Daughters High School Graduation
Messages
1,617
Location
Upstate SC, USA
My testosterone levels dropped when I became ill with CFS. Initially it was total testosterone that was dropping while my direct testosterone was remaining stable, but in the lower end of the normal range. Physician did not want to start any replacement therapy at this point because his point of view was the direct testosterone was the most important. My research finds this view very controversial as some believe the total is just as important as direct. Anyway, as my total kept on slowly trending downward and it eventually dropped below "normal ranges" per Labcorp. Side note here - Labcorps normal range is a very wide range over a wide age range, so you kind of have to place yourself within that matrix to really come close to your normal values. I think it was the test after my first below normal "total testosterone", that my "direct testosterone" started down slowly. Also, during this period of my illness I developed severe muscle pains that to me was like a mobilized cancer that was floating around in my body and not missing a single muscle group. At this point I was placed on a low "time-released" opiate pain killer. My very next testosterone test was the largest single drop since tracking it had started. Total and direct testosterone were both significant enough below "normal values" that I started the 5mg. Androgel therapy and have been on it for 3 years now. I have researched and discovered that in fact opiate pain medication negatively impacts testosterone levels. Opiate pain medications also affect cortisol levels as well, but in a different way. With the cortisol, it's effects are harder to determine because the resting or unstressed 8:00 am reading maybe normal, but what it impairs is the stress response as in if you were present with a very stressful situation which would typically cause a rapid spike in cortisol will not happen if you are on opiate medications. Bare in mind that this is for chronic use of pain medication because there is a well documented change in the HPG and HPA axis after about for 6-8 weeks of pain management therapy.
On another hand there is a pretty organized thinking, view or effort now to not have the direct testosterone replacement be the first line of treatment. Pregnolone and DHEA are suggested first, then possibly using HCG to stimulate the testicles to get the testosterone values up. I think there are some meds out now that they using "probably off label" that is getting attention. I think that most of this is spurred by the fact that once you start the pure testosterone replacement, whether it is with gels, patches or shots(these are considered last resort now) that after 6 weeks it will be a life long thing.
As with cortisol, I keep Cortef at the house and I take it based on what is happening at the moment and never over 10mg at one time.
My concern is what is this testosterone evolving into within my body. I can't get my endocrinologist to even test my estrogen levels (I do feel they are elevated some). I'm pretty sure that I had read that that Androgel can increase your levels of DHT as well.
Kind of feels like a double edge sword and no matter how you go your going to get cut!
 
C

cold_taste_of_tears

Guest
Would this explain maybe (over time) that some people with ME (CFIDS) stabalise from the extreme end of disabilty to severe end ....?

Theory: If hormone levels dropped due to getting older?

E.g Age 18 vs age 38?
 

usedtobeperkytina

Senior Member
Messages
1,479
Location
Clay, Alabama
Well

All I can say is that the two major things that affect my fatigue levels are not pacing and hormone levels. After having the continuous virus, my symptoms were associated with my period. For two and a half years, doctor tried to adjust my birth control pills, tested me for menopause even though I was 39. Finally he put me on three days of estrogen each month, just based on my symptoms. He said my estrogen was falling too low.

But the symptoms stayed and expanded to more days of the month, cognitive problems started, then the plummet with pain.

Even today, I can mark off the days before my period and three days into my period as my being totally disabled from the fatigue.

I too have adult acne, and never did not have it. I went through the topical treatments. One would work for three years, and then it would stop working. Then they tried another one. It worked for about three years. Then it stopped working. Basically, the bacteria was developing a resistance.

Once I tried tetracycline (long before I had CFS) and it gave me a vaginal yeast infection. I used to not like medicine. I just couldn't understand taking another pill to fix what the first pill was causing. So I refused to take it, stopped the tetracycline and never took it again.

I had normal, but on the low end, level of testosterone. And the FFC doctor gave me testosterone cream. My acne got so bad. I had it in my scalp. I lowered the dose. But I still had it real bad. So I stopped it. And I still had it bad, worse than before the testosterone, but not as bad as while I was on it. I get cysts on my chin, my forehead and my back.

My new skin doctor suggested it. I refused. So I went and bought a whole bunch of over the counter anti-acne stuff. And now, as soon as I come home, I wash my face (get off all the makeup). If I am home all day, I wash my face three or four times a month. Yet, about one week out of the month, no matter what I do, it appears.

I do think the hormone activates XMRV, and that explains why perimenopausal women (with fluctuations in hormones) and teenagers (with wild fluctuations in hormones) are more likely to come down with XMRV.

So maybe that testosterone was bad for me. And I was on bio-identical progesterone for a while too. Did that make the virus worse?

So many questions.

Tina
 

meandthecat

Senior Member
Messages
206
Location
West country UK
DHEA and Prostate cancer

Living in the UK ( with some of the worst cancer survival rates in europe) testing is seen as an expensive luxury especially with cfs/me so it's hard to build up a personal picture of what might be going on inside.

Over 6 months of using DHEA I have felt transformed, it's not a miracle cure but I feel like me again. If I stop, I crash over a couple of days and it will take a similar time to recover once I begin again. So it's doing something!

I found conflicting opinions as to the safety, but on balance it seemed worth the risk.. and it is for I have had 6 months of 'life'. What I had before was not life.

I had a PSA(prostate specific antigen) test tacked onto thyroid testing and it came back high( not definitive for cancer, but not good) and so I wonder as a I look along a road of testing and intervention whether they might look for XMRV, or if they have even heard of it.

Nothing is definite but even for a connoisseur of irony this seems a bit rich. I am trying to marshal my resources so that I can make good decisions when the time comes; for I have lost all faith in Doctors competence within the NHS if they have to think outside of the box.

So many people here seem to understand far more than I do that perhaps something might spring to mind. ed
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Hi All. I'd posted some of this in a previous thread discussing cholesterol.

"Interesting. My cholesterol has also tested high in recent years (7 in UK parlance). But I wonder if this is necessarily a 'bad' thing or if the cholesterol may be a side effect.

My illness started in 1986 and around that time I had a lot of blood tests (no record of cholesterol unfortunately). However in 1986 my testosterone level was 25 nmol/L (reference range for males all ages = 10.5 to 30) and by 2000 had fallen to 11.1 - still within the normal range but very low for me. Apparently testosterone normally falls by 25% from peak in the early 20s to aged 75! Around the late 90s (aged 34) I suddenly developed a whole range of new symptoms including rapid weight gain, rapid greying, growing ear hair and prostate problems - both of which are associated with DHT plus hot flushes suggestive of the male menopause (viropause).

Cholesterol rather than just being a nuisance is the building block material for all the steroid hormones including the sex hormones and it is well known that feedback loops continually regulate the level of hormones/neurotransmitters etc in response to needs.

The literature I've read on the viropause lists many symptoms similar to ME symptoms including loss of exercise tolerance, depression, anxiety etc and high cholesterol and heart disease. Interestingly testosterone supplementation is said to reverse these changes including a reduction of testosterone levels to normal.

On the other hand, statins (which reduce the level of available cholesterol) are known in rare cases to cause ME symptoms in previously 'healthy' patients and in a large number of patients fatigue is a side effect.

Is it possible that cholesterol levels are automatically raised in an effort to support the production of steroid hormones which is the main problem rather than the cholesterol? Certainly neuro-endocrine dysfunction is a common finding in ME."

On the basis of this admittedly ropey theory I now take a zinc/magnesium supplement to try to boost testosterone levels and grape seed extract to prevent aromatisation to oestrogen. I haven't had any tests in recent years but I feel much less 'gyny' and even my hair has started reverting back from grey!
 

liverock

Senior Member
Messages
748
Location
UK
On the other hand, statins (which reduce the level of available cholesterol) are known in rare cases to cause ME symptoms in previously 'healthy' patients and in a large number of patients fatigue is a side effect

Statins deplete Ubiquinol (COQ10) which is an essential nutrient for mitochondria energy production, particularly the heart, which has a high number of mito's. Long term use of statins IMO, are one of the main factors responsible for the epidemic proportions of congestive heart failure, a disease where the heart gradually loses energy.

Furthermore, DHT stimulated XMRV replication by 3-fold, whereas androgen inhibitors (casodex and flutamide) suppressed viral growth up to 3-fold. Findings suggest that integration of the XMRV LTR into host DNA could impart androgen stimulation on cellular genes."

If DHT is the main reason for the increase in XMRV levels in the case of CFS, I would have thought there would be be more men than women with CFS with the 50:1 higher ratio of testosterone, even allowing for the women's increased sensitivity to T. Instead it appears that women suffer with CFS around 3 times more than men.

I have taken saw palmetto, beta-sitosterol and pumkins seeds for years, all DHT inhibitors, and they havent done zilch for my CFS (though they probably have been good for the prostate.:))
 
C

cold_taste_of_tears

Guest
Oestrogen is linked to XMRV.

Women have far higher Oestrogen than men.