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Alpha-MSH protein, a potential biomarker for CFS - Japan

Discussion in 'Latest ME/CFS Research' started by DysautonomiaXMRV, Jan 11, 2010.

  1. Source: Daily Yomiuri Online (Japan)
    Date: January 11, 2010
    URL: http://www.yomiuri.co.jp/dy/national/20100111TDY03103.htm


    Breakthrough made in diagnosing chronic fatigue syndrome

    Researchers have discovered a protein in blood that can be used to diagnose chronic fatigue syndrome, a breakthrough that could help detect the ailment during physical checkups.

    There are diagnostic criteria for chronic fatigue syndrome - a disorder involving extreme fatigue of unknown cause that continues for at least six months--that rely primarily on subjective symptoms, but there have been no objective markers such as blood tests. The research team led by Hiroshi Kiyama, a professor of anatomy at Osaka City University, examined the intermediate lobes of the pituitary glands of rats in which they induced extreme fatigue by making them exercise for five consecutive days. They found that the lobes excreted extraordinarily high amounts of a protein called alpha-MSH and that alpha-MSH levels in the animals' blood also increased. The neurotransmitter dopamine inhibits the secretion of alpha-MSH, but the rats' ability to produce dopamine declined as their fatigue grew.

    The group also tested the levels of alpha-MSH in the blood of 57 people diagnosed with chronic fatigue syndrome and the blood of 30 healthy people. The average level among the 37 people who had been diagnosed with chronic fatigue syndrome less than five years before was about 50 percent higher than the healthy people.
    =============================================================================

    Source: Journal of Neurochemistry
    Vol. 109, #5, pp 1389-1399
    Date: March 23, 2009
    URL:
    http://www3.interscience.wiley.com/journal/122270951/abstract?CRETRY=1&SRETRY=0
    Ref: All Hiroshi Kiyama papers,
    http://www.ncbi.nlm.nih.gov/pubmed?term="Kiyama H"[Author]
    All Hiroshi Kiyama papers on alpha-MSH,

    http://www.ncbi.nlm.nih.gov/pubmed?term="Kiyama H"[Author] alpha-MSH
    Rem: Please note that this might not be the research reported in
    todays press release.

    Chronic stress elicits prolonged activation of alpha-MSH secretion and subsequent degeneration of melanotroph.
    ------------------------------------------------------------------
    Ogawa(*,**), Nobue Shishioh-Ikejima(*,**), Hiroyuki Konishi(*,**),
    Tetsuya Makino(*,**), Hiroyoshi Sei(***), Sumiko Kiryu-Seo*,**),
    Masaaki Tanaka(**,****), Yasuyoshi Watanabe(**,****), and Hiroshi
    Kiyama(*,**,+)
    * Department of Anatomy & Neurobiology, Graduate School of Medicine,
    Osaka City University, Osaka, Japan
    ** The 21st Century COE Program 'Base to Overcome Fatigue', Graduate
    School of Medicine, Osaka City University, Osaka, Japan
    *** Department of Integrative Physiology, Institute of Health
    Biosciences, The University of Tokushima Graduate School, Tokushima,
    Japan
    **** Department of Physiology, Graduate School of Medicine, Osaka
    City University, Osaka, Japan
    + Address correspondence and reprint requests to Hiroshi Kiyama,
    Department of Anatomy and Neurobiology, Graduate School of Medicine,
    Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585
    Japan. E-mail: kiyama@...


    Abstract

    Prolonged stress affects homeostasis in various organs and induces stress-associated disorders. We examined the cellular changes of pituitary gland under the continuous stress condition using a rat model in which rats were kept in a cage filled with water to a height of 1.5 cm for up to 5 days. Among the pituitary hormone mRNAs, proopiomelanocortin mRNA was up-regulated specifically in the intermediate lobe (IL) of this rat model. Additionally, the peripheral blood levels of alpha-melanocyte stimulating hormone (alpha-MSH), a major product of proopiomelanocortin in IL were increased. The alpha-MSH secreting cells, melanotrophs, showed a markedly developed endoplasmic reticulum and Golgi apparatus in the early phase of the experiment. Subsequent continuous stress caused remarkable dilation of the endoplasmic reticulum, disruption of the Golgi structure, and the degeneration of some melanotrophs. In addition the dopaminergic nerve fibers from hypothalamus were markedly decreased in IL. A dopamine antagonist elicited the similar morphologic changes of melanotroph in normal rat. These findings suggest that prolonged stress suppressed hypothalamus-derived dopamine release in IL, which elicited over-secretion of alpha-MSH from the melanotrophs. The present study also suggests that prolonged hyperactivation of endocrine cells could lead to disorder of secretion mechanisms and eventual degeneration.
  2. maryb

    maryb Senior Member

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    VERY interesting - hope other scientists around the world will think so too.
  3. Katie

    Katie Guest


    I'm no scientist but this is my take.

    Firstly, this study seems to focus on short term stress as the rats in the study were placed in a five-day discomfort/stress situation. Unless you theorise that we remain in a constant 'stress' state which would suggest a psychological factor as the stress factor on the rats was external, not an internal virus/neurological issue etc. Although outside stress situations can and do cause internal issues, this study seems to posit that it is our reaction to outside stressors that create the upregulation. They do talk about continued stress but I would find this study more relevant to those suffering from PTSD than myself. I know I'm writing like I know what I'm talking about, but this is my first true bash at critiquing a study so I'm totally open to someone telling me that I should reinstate my tagline of Bovine Scatology Phd. :)

    While I am open to stress studies, I've certainly seen variable deterioration in my health under stress but my emotional stress is not necessarily separate from pushing too hard and running on adrenaline which I can do for an impressively long time before spectacularly crashing like a forklift driver in a vodka storage facility ;) I'm concerned that this study supports a neuropsychiatric basis rather than a purely neurological one. Anyone want to correct me on that? What it could mean is that some cases of ME/Cfs are triggered by high stress situations which leads to hyperactivation of endocrine cells. I have in my time seen at least two cases of ME which turned out to have a psychological basis. I do not think of them any differently from anyone else with ME as they experienced the same symptoms as I did, but for different reasons. It makes not a jot of difference to me personally, but the more we organise the wastebasket the better for future studies and cohorts.
  4. fresh_eyes

    fresh_eyes happy to be here

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    mountains of north carolina
    Interesting take, Katie. I read it as saying that the fatigue of CFS sufferers is chemically the same as fatigue caused by extreme exertion, and can be tested for.

    But you may be right - I do get a red flag from "stress-associated disorders".
  5. acer2000

    acer2000 Senior Member

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    The curious thing about this study is that it seems to be reporting the opposite of what Dr. Shoemaker claims. Although things may change over time with the illness... ie high MSH to begin with and then over time it falls. Interesting though...
  6. lostinthedesert

    lostinthedesert Killer, Clown, Priestess

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    When I crashed hard almost 20 years after I first got sick, I had very low MSH. Don't know where I am now...waiting for results. I have heard of some people who had low MSH who were still sick after it came back up. I also know of some mold patients who said they have tried MSH analogs like melanotan2 with no improvement.

    Peace,
    S
  7. Nina

    Nina Senior Member

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    I'm pretty sure that whatever they measured there is not what we are experiencing.

    Haven't you all had the situation where you needed to explain what your exhaustion and weakness feels like?

    My reply to that is often that it's very much like wanting to explain the colour yellow to someone who has been blind since birth. There has been nothing in my life before this disease that felt even remotely close to what I am feeling now. Not even runnning a marathon after not having slept for 3 nights... it's just not like anything a healthy person would ever feel like.

    Just my 2 cents.
  8. Nina

    Nina Senior Member

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    Sorry, double post!
  9. Tammie

    Tammie Senior Member

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    Woodridge, IL
    I'm not quite sure of my understanding overall of the study bc it does seem to contradict other findings, and bc it does seem focused on short term exertion (and only how that impacts fatigue levels, and as we know CFS is much more than just fatigue)....however, just considering the above quote, if your take is correct, it immediately brings to mind my own experiences (pre-CFS) with running 26.2 mile marathons. I would say those qualify as extreme exertion, and I can honestly say that I felt substantially better in the minutes, hours, and days following running marathons than I do on a regular basis after a full night's (admittedly very fitful) sleep with CFS. So, even if the body's response appears similar, there is still something significantly different between the two things they are measuring.
  10. Tammie

    Tammie Senior Member

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    Woodridge, IL
    Interesting - I had not read this response when I posted my first response to this thread (I mentioned marathons in it)

    anyway, just wanted to comment that the comparison to explaining the color yellow is a great way to put it

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