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Thyrotropin Releasing Hormone (TRH) Overview (also known as Protirelin)
TRH, also frequently referred to as Protirelin, is a small peptide hormone produced in the hypothalamus. Its main functions are to stimulate the release of both thyroid-stimulating hormone and prolactin from the anterior pituitary. TRH is used clinically to test the function of the anterior pituitary gland in the work-up of thyroid disorders. Research shows that TRH has anti-depressant and anti-suicidal properties. It also likely plays roles in regulating the aging process, arousal, feeding behavior, autonomic regulation, and fighting free radical damage.
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Molecular Formula: C16H22N6O4
Molecular Weight: 362.39 g/mol
PubChem CID: 638678
CAS Number: 24305-27-9
Synonyms: Protirelin, Thyroliberin, Lopremone, Relefact
TRH and Depression
Thyrotropin releasing hormone has long been speculated to have anti-depressant effects. In fact, the U.S. Army awarded a research grant to the Indiana University School of Medicine in 2012 to develop a TRH-based nasal spray to prevent suicide among soldiers. The knowledge, however, that TRH can reduce suicidal ideation has been around since at least the 1970s.
In an early study, doctors administered TRH directly into the spines of patients suffering from severe depression. Five of the eight patients tested responded favorably, showing a 50% or greater reduction in the symptoms of depression as well as a significant reduction in thoughts of suicide. Though the results were dramatic, the short half-life of TRH meant that they did not last long. This study was, however, extended in a trial looking at the effects of TRH in depressed women. In this study, TRH was again effective, but appeared to be more effective in women with a specific kind of depression that had no symptoms of anxiety. Researchers speculated that the specific effects of TRH in depression may be related to a patient’s emotional state.
Of course, spinal administration of TRH is not a convenient means of treating depression and so research was done to determine if the peptide could be just as effective when administered by IV. As it turns out, the peptide does cross the blood-brain barrier and so IV administration is just as effective as intrathecal administration. Still, IV administration is impractical for most people and that is why the army is funding research to develop a version of TRH that can be administered intranasally.
Interestingly, research in bipolar patients has shown that TRH has more profound effects on depression when given at night. Researchers speculate that this may be because nocturnal administration fits better with the natural circadian cycling of TRH. In the study, size percent of those given TRH showed a 50% or greater reduction in symptoms of depression, which is in keeping with other studies. What was different, however, was that the effects lasted for up to 48 hours, far longer than the antidepressant effects of TRH in other studies. Extending the duration of action of TRH via nocturnal administration could make it practical not only to use the peptide, but to administer it via injection.
TRH Research and Motor Memory
Motor memory, also called muscle memory, refers to a form of procedural memory that develops as a result of doing a specific motor task over and over again. Examples include learning to type on a keyboard, learning to ride a bicycle, and playing a musical instrument. This type of memory differs from rote memory (the ability to learn facts) in a number of ways and is encoded primarily in the cerebellum. The cerebellum is a separate region of the hindbrain that is critical to motor control, coordination, equilibrium, and posture.
Research in mice lacking the gene for TRH has shown that they are slower to learn specific motor tasks, but that learning speed can be increased via exogenous administration of TRH. These findings confirm a long-held suspicion that TRH is active in the cerebellum and likely plays a role in facilitating motor learning.
Knockout mice treated with TRH learned much faster after four trials, with time before falling from rotating rod being nearly twice that of untreated mice. This shows improved rates of motor learning
Additional research in mice suggests that TRH supplementation may help to reduce the effects of diseases that impact the cerebellum. For instance, TRH and TRH analogues have been found to decrease ataxia in models of human cerebellar degenerative disease. They appear to do so directly, via their effect on motor learning, as well as indirectly by increasing arousal and reducing the effects of depression.
TRH Research to Help Fight Opioid Overdose
Opioids, such as heroin and Oxycontin, can be deadly in the setting of overdose because they suppress the respiratory drive (urge to breathe) in the brainstem. To date, the best available treatment for an opioid overdose is a drug called naloxone (Narcan). Narcan is highly effective, but reverses not only the respiratory effects of opioids, but their pain-controlling effects as well. This can be a serious problem in people who suffer from chronic pain.
New research in rodents shows that TRH increases both blood pressure and breathing rate. When given intravenously or spraying it directly into the lungs, TRH boosted breathing rates in a dose-dependent manner without affecting pain control. The peptide prevented death in all animals it was given to. TRH could become a mainstay of the fight against opioid overdose because it provides the same benefits of naloxone with fewer side effects. In addition, it appears that the two treatments have different mechanisms of action, meaning they might be able to be used synergistically, and that one can be given if the other fails.
TRH Analogue Tested in Trauma
Taltirelin, a metabolically more stable version of TRH and one with a longer half-life, has been tested in the setting of acute hemorrhagic shock in rats. Preliminary results show that TRH can help to improve mean arterial blood pressure and respiratory rate, results that are similar to existing treatments for acute blood loss. TRH also improved the pH of blood and prevented a decrease in arterial oxygen saturation, making it a useful adjuvant in the treatment of blood loss and hypovolemic shock. Because of its limited side effect profile, TRH could become a mainstay of emergency shock treatment in ambulances.
TRH Deficiency Important in Disease Development
It has long been known that changes in TRH levels are associated with thyroid disease, but researchers and doctors have also observed that changes in TRH and other thyroid hormones also occur in a variety of non-thyroid illnesses. Research in rats has revealed that specific neurons in the brain may be responsible for this phenomenon as they lose the ability to produce TRH and respond to feedback mechanisms. There is interest in whether TRH supplementation may be able to reduce the severity of non-thyroidal illness in some instances and act as an adjuvant to more directed therapies.
TRH May Affect the Aging Process
Research in mice has shown that TRH can help to protect certain organs against oxidative damage and natural aging. It appears that TRH reduces the building up of amyloid plaque in the kidneys, a common cause of reduced kidney function as humans age. By preventing the buildup of this plaque, TRH appears to preserve kidney function despite advancing age. Similar effects are seen in the testes of aging male mice.
Of course, amyloid plaques are most clearly associated with Alzheimer’s disease (AD) and so it should come as no surprise that researchers are interested in the ability of TRH to prevent amyloid buildup in the brain the same way that it does in the kidneys. Preliminary studies in mice have yielded unclear results. Why TRH does seem to increase arousal in aging mice, it isn’t clear if it has any impact on amyloid plaque buildup.
That said, research suggests that TRH levels drop in the hippocampus of patients suffering from AD, suggesting that supplementation may be of use even if TRH has no impact on amyloid buildup in the brain. According to Luguang Luo, lead author of the paper and professor of regenerative medicine, “TRH within the hippocampus can regulate the activity of various proteins by phosphorylation/dephosphorylation that may be involved in the pathogenesis of AD.”
Protirelin exhibits minimal side effects, high oral and excellent subcutaneous bioavailability in mice. Per kg dosage in mice does not scale to humans. TRH for sale at USA Peptide Store is limited to educational and scientific research only, not for human consumption. Only buy Thyrotropin releasing hormone if you are a licensed researcher.
TRH (Thyrotropin Releasing Hormone) (Protirelin Acetate)
Anti-Aging Properties of Thyrotropin Releasing Hormone TRH By DR WALTER PIERPAOLI MD 2012 THE YEAR OF THE FOUNTAIN OF YOUTH MOLECULE – TRH – DR WALER PIERPAOLI MD – SWITZERLAND AND ITALIAN RESEARCH LABS AND CLINICS .. A4M AMERICAN ACADEMY OF ANTIAGING MEDICINE Aging-Reversing Properties of Thyrotropin Releasing Hormone (TRH) Walter Pierpaoli, MD, PhD Interbion Foundation for Basic Biomedical Research (TRH Absrtact):
Previous work from our laboratory prompted us to study the effects of short-term, acute administration of TRH or its chronic oral administration, on organs, tissues and aging-related metabolic and hormonal markers, in order to acquire more knowledge on effects, dosage and timing of administration according to its circadian cyclicity. In addition, we wanted to verify its anti-aging effects on two most fundamental functions, namely gonadal- reproductive and kidney-urinary. The results demonstrate that both a short-term, acute or a chronic, long-term oral administration of TRH to old, aging mice, results into positive changes and rapid correction to more juvenile levels of most typical aging-related hormonal and metabolic alterations.
Remarkably, 4-month oral treatment with TRH maintains testes function in aging mice. As hinted by the significant increase of testes weight, TRH taken from the drinking water produces a maintenance and/or reconstitution of testes structure and function as shown by active proliferation and formation of mature spermatogonia and intensive spermatogenesis in the follicles. 4-month oral treatment with TRH protects the kidneys from amyloid and hyalin infiltration of both tubuli and glomeruli, which is typical of aging mice. In fact, massive deposits of amyloid and hyalin material are clearly infiltrating the shrunken glomeruli of untreated mice with loss of filtration capacity, while hardly present in TRH-treated mice. Massive hyalin degeneration can also be observed in the tubular vessels of the untreated control mice.
These experiments with parenteral and oral administration of TRH show a most remarkable aging-delaying and apparently even aging-reversing effects of the neuropeptide TRH. Again, similarly to melatonin, we are confronted with an anti-aging agent with a broad spectrum of activities which must be necessarily linked to a most fundamental role in the regulation of metabolic and hormonal functions. Aging-Reversing Properties of Thyrotropin Releasing Hormone (TRH) What is TRH? TRH also know as “Thyrotropin Releasing Hormone”, carries the unfortunate and highly misleading designation of a Thyroid releasing hormone. It is a ubiquitous tiny molecule composed of three amino acids and it can be found everywhere in nature, from unicellular algae to the complex mammalian species.
In man, it is concentrated in certain areas of the anterior hypothalamus and the pineal gland in the brain, and in the insulin-producing beta cells in the pancreas. Even at very high concentration and injected by the intravenous route, no side-effects whatsoever or noxious effects have ever been observed. Since its discovery in the 50s by the Nobel Prize Roger Guillemin, hundreds of publications have documented an amazing number of positive effects. However, its short half-life has prevented its extensive clinical use, since TRH is rapidly destroyed in the stomach and in the gut.
Therefore Sub Cutaneous administration has been shown to be advantageous. What does TRH do? In the years 1989-1990, Dr. Walter Pierpaoli published his first relevant paper describing the amazing variety of effects of TRH in the reconstitution of the thymus – the master gland for the immune system which naturally declines during aging, and its anti-viral effects against a lethal virus. However, all the effects of TRH are not simply produced by an increase of thyroid hormones. Later on additional publications have illustrated TRH and it’s anti-aging effects.
Recently, Dr. Pierpaoli has demonstrated with different obesity models in mice how TRH is able to reverse and abrogate aging related adiposity and correct aging-related hormonal alterations by acting directly on the hormones regulating fat stores. He has also observed that TRH produces a rapid mobilization of triglycerides in the blood, a decrease of leptin and consequently a rapid loss of body weight.
Dr. Pierpaoli has suggested that TRH may constitute a key element in the hormone-controlled regulation of body weight and fat stores. This mechanism is fundamental for the maintenance of body weight, whose control is progressively weakened with age. At the 5th Stromboli Conference on Aging and Cancer in June 2010, Dr. Pierpaoli illustrated the amazing variety of aging-reversing activities of TRH with clear-cut evidence at various levels.
Besides observing a correction to juvenile levels of all parameters measured, Dr. Pierpaoli was able to produce a total correction of two typical aging-related degenerative processes, namely a reversal of testis atrophy with restoration of spermatozoa production and maturation, and a total recovery of kidney function with maintenance of glomerular filtration and tubular function, as shown by disappearance of hyalin and amyloid infiltration which are typical of kidney degeneration during aging.
In order to verify the aging-reversing affects of TRH, we suggest the measurement of some simple blood parameters such as glycemia and triglycerides before use. Conclusion: Dr. Poerpaoli’s research suggests that TRH is a master hormone responsible not just for helping to adjust thyroid hormones (its principle recognised role), but in helping to recorrect many imbalances throughout the body.
For example in his animal experiments TRH supplements have encouraged old animals to: Re-establish spermatogenesis, (reversing the age-related dysfunction of their testes) Correct kidney dysfunction, (a significant finding for renal issues) Correct pancreatic dysfunction, (a significant finding for diabetic issues) Act as an anti-cancer/protective agent Lose significant fat deposits and hence weight within 2 to 3 months Dr. Pierpaoli intends to release a book in 2011 describing his patients & results and exposing the published literature on this remarkable agent.
Research has shown that after one month of daily use, both blood sugar levels and Triglyceride levels were significantly lower. The loss of body fat will follow in the course of the treatment but, a few months are necessary to observe how the new metabolic and juvenile pathways will result in aging reversal and visceral fat reduction.
Molecular formula: C16H22N6O4
Molar Mass: 362.38367 g/mol
CAS number: 24305-27-9
PubChem: CID 439302
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