Researchers Identify Testosterone-triggered Molecule that Protects Men from MS

Researchers Identify Testosterone-triggered Molecule that Protects Men from MS

A molecule triggered by the male hormone testosterone protects male mice from developing multiple sclerosis, Northwestern Medicine researchers report.

Their discovery may help explain why MS affects more women than men. It could also lead to targeted therapies to protect women against the disease.

The study, “Male-specific IL-33 expression regulates sex-dimorphic EAE susceptibility,” appeared in the journal Proceedings of the National Academy of Sciences.

The incidence of MS is three to four times higher in women than in men. Sex also determines the age at which the disease strikes and the course it takes.

Scientists knew these differences stemmed from the much higher testosterone levels in men, but they didn’t know the mechanism that caused the difference.

A research team led by Melissa Brown, a microbiology and immunology professor at Northwestern University’s Feinberg School of Medicine, used mice models of MS to explore the subject.

They found that, in male mice, testosterone could prompt immune cells called mast cells to produce the signaling molecule interleukin-33, or IL-33. The molecule promoted a cascade of cell signals that prevented the activation of inflammation-generating Th17 immune cells. Th17 cells play a key role in the destruction of nerve cells’ protective myelin layer — a hallmark of MS.

To further demonstrate IL-33’s nerve-cell-protective effect, the team blocked the activity of the molecule in male mice. This led to their MS symptoms quickly worsening.

Next the team did tests to see if the molecule could protect females. When they administrated IL-33 to female mice in the early stages of MS, the animals’ symptoms diminished significantly.

In addition, IL-33 reversed the symptoms of female mice with full-blown MS.

“Because testosterone levels are seven to eight times lower in adult women compared to men, we speculate there are insufficient levels in females to activate this protective pathway,” Brown said in a news release. “But we showed we can activate the pathway with the guardian molecule IL-33.”

Brown hopes the discovery leads to “an entirely new kind of therapy for MS.”

“IL-33 therapy has the potential to prevent disease progression by blocking damaging inflammation as well as promoting myelin and neuronal [nerve cell] repair in MS and other” central nervous system diseases, the researchers concluded.


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  1. Jane Shanahan says:

    I would like to know more about your study as I feel that hormones play a big part in MS and how your body deals with the disease.

    They could be the medicine that is needed to help alleviate symptoms, disease progression and a possible cure.

    Please, please continue your studies and keep us all posted.

    Thank you,

  2. Anna Chafe says:

    I agree with Jane… as I have always said to my Nuerologist when I get my period I have always felt great thinking it was hormone related. Just the mere fact that more women have MS than men is a red flag. Please, please keep your eye on this story. Anna Chafe

  3. Kelly says:

    I caught my MS extremely early- during an active spinal lesion, with two previous brain lesions. About one year earlier I was having dibilitating migraines once a month during my period and was diagnosed with estrogen withdrawal migraines- prescribed a hormone patch… I had stomach issues for ten years prior to that which I repeatedly discussed with my Dr at the time as being worse with my period… I know there’s a hormone connection but there are so many pieces to the puzzle. I feel like I caught mine so early on and I am so mindful in general of my timeline of symptoms that a lot could possibly be figured out with my story but that’s not how all this works lol. Drs are the experts who we are expected to listen to…why would we have anything of value to share about the disease we live with every day?

  4. Joe says:

    Mouse model of MS ≠ MS. Therein lies the problem with 95% of todays research…It might be a useful model if you want to try to milden symptoms, which is very profitable, but will never ever cure anything.

  5. Joe says:

    And since it is a different disease altogether there is not guarantee that what works in mouse model MS would work at all in real MS.

    • Christopher says:

      No, there’s no guarantee. But the results are very close to what can be applicable to humans. Also the mouse testing isn’t done to be able to see direct effects in humans–that’s widely misunderstood. It’s just a preliminary step in a long process.

  6. Heracles says:

    They have known for a long time that women with MS have lower testosterone levels than disease-free women. Men with MS that were given testosterone grew back grey matter. Women also lose testosterone as they age and those with MS likely worsen because of this deficit. Among several things, it is well understood that Testosterone is an anti-inflammatory hormone. Men have been given testosterone replacement safely for many years. Recently, post-menopausal women have also been safely receiving testosterone.
    The only reason that this has not been pursued even earlier is that there is no big money for Big Pharma in a hormone that they cannot patent and sell for crazy money. Could it be that many women and men that suffer from MS simply have an overactive immune system and lower levels of testosterone…hmmm??? Vitamin D has been seen to raise testosterone; maybe that is why it also seems to help MS sufferers…

    • Christopher says:

      The “Big Pharma” comment isn’t actually correct. Companies already work with testosterone. If you’re looking for a cause of MS, it’s much more complex than just connecting the dots. MS is a multi-factorial condition, and the etiology and pathology of MS is different in each person. MS involves multiple systems where the communication has become dysfunctional… so just taking supplements and HRT probably wouldn’t do too much. I know a lot of people are frustrated and discouraged by the timeliness of MS treatment progress. But be assured that many well-intentioned and talented people are working very hard to cure this awful disease. The premise that all large pharmaceutical companies are only involved as a matter of self-interest is just not true. Some may be, or act that way, but it’s not universal.

    • Mike says:

      Heracles your right testosterone plays a very important part. I been getting the replacement therapy for a year now and what a difference I feel. I do have spasticity but i deal with it taking Baclofen 20mg. But let me tell you a good proper diet Vitamins exercise and testosterone help so much.

  7. Mike says:

    I have been on Testosterone now for a year now I get the injections once a week plus do HGC to prevents testicular atrophy. Since I been getting the injection I feel so strong I had low T with my levels at 286 now there at 941 plus I exercise 6 times a week. I do a lot of weight training which helps with with my strength. I am also on Ocrelizumab which is given by infusion twice a year. That has helped keep my MS at bay. But I truly believe that the testosterone really plays such an import role against this disease. I’m hoping that a drug comes to market that helps remyelination on nerves.

  8. PTM says:

    Christopher, you may or may not know that there is a difference between natural bio identical hormones and synthetics. Big Pharma wants to mass produce for the cheapest cost possible without regard for what’s best for the patient. Synthetics have different reactions than bio identical. Example, my Dad has ALS. I have researched low B12 and found it causes ALS like symptoms from long term low levels. They have 4 types of B12. The best most natural being methylcobalomin. Only purchased at a compound pharmacy and better absorbed via injection into the muscle. The other, more widely used commercially, is Cyanocobalamin. Guess what, this kind has trace amounts of cyanide. When your body is already fighting do you want to add cyanide? No! Hormones play a huge part in how our bodies act. I won’t go into the long details of my husbands experience but we saved his life spending some time researching and understanding. You’d be amazed at what is approved by the FDA as safe. In the meantime, I am going to suggest bio identical testosterone injections for my Dad along with his methylcobalomin injections to strengthen his muscles. Everyone should read the book Could It Be Low B12. It’s so eye opening for good health.

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