More on MSH

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MSH FACT SHEET

Q: What is alpha melanocyte stimulating hormone (MSH)?

A: MSH is an anti-inflammatory, regulatory hormone made in thehypothalamus. It controls production of hormones, modulates the immunesystem and controls nerve function, too. It is made when leptin is ableto activate its receptor in the proopio-melanocortin (POMC) pathway. Ifthe receptor is damaged by peripheral immune effects, such as therelease of too many pro- inflammatory cytokines, then the receptordoesn't work right and MSH isn't made. Leptin controls storage of fattyacids as fat, so MSH and leptin are a major source of interest.

Q: Isn't this damage to the leptin receptor just like what we see in insulin resistance?

A: Actually, the mechanism is almost identical. A lot of our obesityand diabetes is inappropriately blamed on overeating when the realproblem is damage to these regulatory receptors.

Q: What does MSH do?

A: MSH sits as the central hubof a series of important effects. MSH controls hypothalamic productionof melatonin and endorphins. Without MSH, deficiency creates chronicnon-restful sleep and chronic increased perception of pain,respectively. MSH deficiency causes chronic fatigue and chronic pain.MSH also controls many protective effects in the skin, gut and mucusmembranes of the nose and lung. It also controls the peripheral releaseof cytokines; when there isn't enough MSH, the peripheral inflammatoryeffects are multiplied. MSH also controls pituitary function, with 60%of MSH deficient patients not having enough antidiuretic hormone. Thesepatients will be thirsty all the time, urinate frequently and oftenwill have unusual sensitivity to static electrical shocks. 40% of MSHdeficient patients won't regulate male hormone production and another40% won't regulate pro- per control of ACTH and cortisol.

Q: What illnesses are associated with MSH deficiency?

A:Any illness that begins with excessive production of pro- inflammatorycytokines will usually cause MSH deficiency. This is the basicmechanism that underlies damage caused by exposure to biologicallyproduced toxins neurotoxins (biotoxins) made by invertebrate organisms,including fungi (molds), dino- flagellates (ciguatera and Pfiesteria),spirochetes (Lyme disease), blue-green algae (Cylindrospermopsis inFlorida and Microcystis all over the world) and bacteria, like anthrax.Nearly 100% of the patients who have Chronic Fatigue Syndrome (CFS)will have MSH deficiency. Do we know that all CFS is due to biotoxins?No.

Q: OK, if something is going on in the body that causesinflammation, like exposure to toxins made by mold in Sick BuildingSyndrome, and the immune system is cranking out these proteins,cytokines, that are great for our health when they are released in theright amount at the right time, but harmful when too many are made atthe wrong time, why don't we just fix the cytokine response and watchMSH get going again?

A: Good question. We are looking at an incredibly small area in thehypothalamus, one in which there is a real risk of permanent damagefrom cytokines to blood flow to this pathway. And who is to say thatthe vital receptors aren't destroyed by too much attack for too long?Once MSH production is damaged too much, it is too late.

Q: So, if the toxin and cytokine illness goes undiagnosed, orsomeone says the illness doesn't exist, like what we have seen for along time with mold and in Lyme disease, there are going to be peoplewhose MSH supply just dwindles down to nothing.

A: Right. These patients are miserable. They live, but there is nolife. They are given Oxycontin or Neurontin or Elavil or Xanax, forexample, but nothing really helps. Families are destroyed, careers areruined, financial resources are poured into tests that mean nothing andtherapies that hopefully won't cause harm, because they never help.Even worse, because MSH levels are rarely measured, many doctors lookat the MSH deficient patients as if they are making up the illness,making up the pain to get drugs or looking for disability. And lots ofthem end up on disability, costing our society not just the unnecessaryexpense but also costing us the lost productivity.

Q: What is the answer for those people who are MSH deficient?Why don't we just give them MSH? It should be so simple, like givinginsulin to a diabetic who needs it, right?

A: Should be, but it isn't. The FDA is real particular about givingpotent hormones like MSH to just anybody. Just look at cortisone. Alittle bit is necessary for life, but too much will kill you. MSH can'tbe given to people until animal toxicity studies are done, showingsafety, and that costs a lot of money, even if the paper work can bedone.

Q: Why don't all the big drug companies jump on this? If whatyou are telling me is that there are a large number of people who willneed daily replacement of MSH, and by the way, it looks like our supplyof Sick Buildings that will generate MSH deficient patients won't dryup any time soon, then there should be a huge market for somebody.

A: No doubt about that. There are companies looking at MSH as we speakfor weight loss, skin pigment changes and as an antidepressant, but noone is looking at MSH in chronic, fatiguing illnesses.

Q: So, if you can raise the money to prove MSH is safe, then what?

A:Researchers at the NIH, like Dr. Star, would likely be willingto help with the experiments in humans. I'm sure there are otheracademic researchers who would come forward, but the problem is thatthe experience of physicians with MSH is so limited. Certainresearchers like Dr. Lipton of Zengen and Dr. Star, who know MSH,know what a huge area of medicine is involved with MSH. But the averageendocrinologist, for example, just doesn't deal with MSH deficiency. Wewill use my database of nearly 2000 patients with illnesses associatedwith MSH deficiency to develop a double blind, placebo controlled,crossover clinical trial after we have done a titration study to provehow much MSH is needed, given in what route, for how long, with whatside effects and with what adverse reactions over time. When our workdemonstrates what I feel it will, then suddenly, there is hope for alarge number of chronically suffering people of all ages.

For more information:

Look on Google for the many aMSH patents in process, chat groups, and new research

Look up MSH in Pubmed and see the thousands of articles on this topic.

Go to www.moldwarriors.com, which is the source of this article from Dr. R. Shoemaker.DR. SCHALLER NEITHER SUPPORTS NOR OPPOSES THE INFORMATION LISTED ABOVE. PLEASE DISCUSS WITH YOUR LICENSED MEDICAL PROFESSIONAL.

MSH or Melanocyte-Stimulating Hormone Basics

MSH is an explosively new hormone that is deficient in many peopledue to inflammation, infections and possible toxin exposures of variouskinds. Some feel it can even be permanently destroyed, but this isunfortunately usually due to very narrow and limited treatmentabilities — fetish medical interests. According to the brilliant leaderin MSH research, who has the two major textbooks on the topic, Dr.Cone, MSH has vast roles in the body — perhaps one reason it is beingmade all over the world with eagerness for many years.

He includes in his The Melanocortin System, from a paper by Hruby,Cai, et. al. (2002) that MSH has some of these sample effects:

Heart Function Benefits

Stress Coping Help

Better Attention and Memory

Cancer and UV Protection, e.g., skin cancer

Addiction Treatment

Neuron Repair

Pain Control

Anti-inflammatory Effects

Weight Control or a Restoration of Normal Eating

Normal Urination

Fever Control

Erection BenefitsAmusingly, some authors act like they have discovered MSH, wheneverything they say about MSH is well-known throughout thepharmaceutical and research world community. One just needs to read thebasics in basic books and articles. Some feel they have discovered alink between Leptin and obesity and MSH. And while these things arerelated, there is no simplistic path, since as the article by Shimizuand others below shows Leptin and MSH are independent in a great manyways.

* * * * *

Nat Neurosci. 2005 May;8(5):571-8.

Anatomy and regulation of the central melanocortin system.

Cone RD.

The central melanocortin system [which makes MSH] is perhaps thebest-characterized neuronal pathway involved in the regulation ofenergy homeostasis. This collection of circuits is unique in having thecapability of sensing signals from a staggering array of hormones, nutrients and afferent neural inputs.It is likely to be involved in integrating long-term adipostaticsignals from leptin and insulin, primarily received by thehypothalamus, with acute signals regulating hunger and satiety,primarily received by the brainstem. The system is also unique from aregulatory point of view in that it is composed of fibers expressingboth agonists and antagonists of melanocortin receptors. Given that thecentral melanocortin system is an active target for development of drugs for the treatment of obesity, diabetes and cachexia, it is important to understand the system in its full complexity, including the likelihood that the system also regulates the cardiovascular and reproductive systems.

J Endocrinol. 2007 Apr;193(1):1-9.

The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure.

Shimizu H, Inoue K, Mori M.

The brain hypothalamus coordinates extra-hypothalamic regions tomaintain energy homeostasis through the regulation of food intake andenergy expenditure. A number of anorexigenic and orexigenic moleculesin the hypothalamic nuclei participate in the control of energyhomeostasis. Leptin and pro-opiomelanocortin (POMC)-derivedalpha-melanocyte-stimulating hormone are key anorectic molecules, andthe leptin receptor and POMC gene are both expressed in thehypothalamic arcuate nucleus. Although it has been considered thatmelanocortin signaling is localized downstream to leptin signaling,data have accumulated to support the concept of a leptin-independentmelanocortin signaling system. We focus on and review the melanocortinsignaling system that functions dependently or independently of leptinsignaling in the regulation of energy homeostasis.

1: Gastroenterology. 2008 Jan;134(1):166-78. Epub 2007 Oct 17.

Related Articles, Links

PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation.

Dalmasso G, Charrier-Hisamuddin L, Thu Nguyen HT, Yan Y, Sitaraman S, Merlin D.

Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.

BACKGROUND & AIMS: KPV is a tripeptide (Lys-Pro-Val), which possessesanti-inflammatory properties; however, its mechanisms of action stillremain unknown. PepT1 is a di/tripeptide transporter normally expressedin the small intestine and induced in colon during inflammatory boweldisease (IBD). The aim of this study was to 1) investigate whether theKPV anti-inflammatory effect is PepT1-mediated in intestinal epithelianand immune cells, and 2) examine the anti-inflammatory effects in twomodels of mice colitis. METHODS: Human intestinal epithelial cellsCaco2-BBE, HT29-Cl.19A, and human T cells (Jurkat) were stimulated withpro-inflammatory cytokines in the present or absence of KPV. KPVanti-inflammatory effect was assessed using a NF-kappaB luciferase genereporter, Western blot, real-time RT-PCR and ELISA. Uptake experimentswere performed using cold KPV as a competitor for PepT1 radiolabelledsubstrate or using [(3)H]KPV to determine kinetic characteristics ofKPV uptake. Anti-inflammatory effect of KPV was also investigated inDSS- and TNBS-induced colitis in mice. KPV was added to drinking waterand inflammation was assessed at the histologic level and byproinflammatory cytokine mRNA expression. RESULTS: Nanomolarconcentrations of KPV inhibit the activation of NF-kappaB and MAPkinase inflammatory signaling pathways, and reduce pro-inflammatorycytokine secretion. We found that KPV acts via PepT1 expressed inimmune and intestinal epithelial cells. Furthermore, oraladministration of KPV reduces the incidence of DSS- and TNBS-inducedcolitis indicated by a decrease in pro-inflammatory cytokineexpression. CONCLUSIONS: This study indicates tht KPV is transportedinto cells by PepT1 and might be a new therapeutic agent for IBD.

Publication Types:

Research Support, N.I.H., Extramural

PMID: 18061177 [PubMed - indexed for MEDLINE]2: Basic Clin Pharmacol Toxicol. 2007 Dec;101(6):416-20.

Related Articles, Links

Functional evaluation of THIQ, a melanocortin 4 receptor agonist, in models of food intake and inflammation.

Muceniece R, Zvejniece L, Vilskersts R, Liepinsh E, Baumane L, Kalvinsh I, Wikberg JE, Dambrova M.

Faculty of Medicine, University of Latvia, Riga, Latvia.

Thecentral melanocortinergic system plays an important role in regulatingdifferent aspects of energy homeostasis and the immunomodulatoryresponse. In the present study, we evaluated the in vivo activities offood intake suppression and anti-inflammatory activity of THIQ, whichhas been proposed to possess high and selective melanocortin-4 receptoragonistic activity in vitro. The results showed that THIQ (0.1, 0.3 and1 nmol/rat, intracerebroventricularly) is less effective in reducingfood intake and body weights of rats than the non-selectivemelanocortin receptor agonist melanotan II. Electron paramagneticresonance measurements in mice brain tissue showed that THIQ at dosesof 0.001 and 0.01 nmol/mouse (intracisternally) increased theconcentration of nitric oxide, which is not typical for melanocortinreceptor agonists. In an experimental brain inflammation model, THIQonly weakly antagonized lipopolysaccharide-induced nitric oxideoverproduction in brain tissue at a dose of 0.01 nmol/mouse. Ourfindings provide new insight into the in vivo pharmacological profileof the in vitro selective melanocortin-4 receptor agonist THIQ and givegrounds for caution when interpreting and predicting melanocortinreceptor selective agonist activity in vivo.

Publication Types:

Comparative Study

Research Support, Non-U.S. Gov't

PMID: 18028105 [PubMed - indexed for MEDLINE]3: J Sex Med. 2007 Nov;4 Suppl 4:269-79.

Related Articles, Links

Bremelanotide: an overview of preclinical CNS effects on female sexual function.

Pfaus J, Giuliano F, Gelez H.

Concordia University-Psychology, Montreal, Canada. Jim.Pfaus@...

INTRODUCTION:Bremelanotide is an analogue of the naturally occurring peptidealpha-melanocyte-stimulating hormone (alpha-MSH). It stimulateserection in men and male rats, and is currently in clinical trials forthe treatment of erectile dysfunction. AIM: To review the effects ofbremelanotide, an analogue of the naturally occurring peptidealpha-MSH, on the preclinical indices of sexual desire in female rats,and where in the brain these actions may occur. MAIN OUTCOME MEASURES:Appetitive sexual behaviors, such as solicitations, hops and darts, andpacing, were assessed along with consummatory behaviors such aslordosis. The involvement of brain regions was assessed followingdirect administration to the region, by the stimulation of molecularmarkers of neural activation, and using microdialysis to examineextracellular fluid for different neurotransmitters. METHODS: Using amodel that allows ovariectomized, hormone-primed female rats to controlthe timing of sexual encounters with males, we tested the ability ofbremelanotide to increase appetitive (proceptive) and/or consummatorysexual behaviors. RESULTS: Bremelanotide dramatically and selectivelyincreased measures of solicitation in female rats, without alteringpacing or lordosis, following both peripheral (subcutaneous)administration or infusions directly into the lateral ventricles ormedial preoptic area (mPOA), but not the ventromedial hypothalamus. ThemPOA is critical for the display of appetitive sexual behaviors infemales and males of a variety of species. Peripheral administration ofbremelanotide activates the mPOA and other hypothalamic and limbicregions of the brain involved in sexual behavior, and may work byactivating dopamine terminals in the mPOA. CONCLUSIONS: To the extentthat solicitations indicate the desire of female rats to engage insexual activity, bremelanotide appears to possess the behavioral,pharmacological, and neuroanatomical specificity required of a drug inthe treatment of hypoactive sexual desire disorders.

PMID: 17958619 [PubMed - indexed for MEDLINE]

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