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TRH Thyrotropin (Protirelin) (25mg)
TRH Thyrotropin (Protirelin) peptides are Synthesized and Lyophilized in the USA.
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What is the TRH Thyrotropin (Protirelin) peptide?
Thyrotropin Releasing Hormone (TRH), often called Protirelin, is a small peptide hormone synthesized in the hypothalamus. It was developed to stimulate the release of both thyroid-stimulating hormones and prolactin from the anterior pituitary. TRH is used clinically to study the function of the anterior pituitary gland during thyroid disorders. TRH appears to have anti-depressant and anti-suicidal properties and may play a role in regulating aging processes, arousal, feeding behaviors, autonomic regulation, and fighting free radical damage.
AKA: Protirelin, Thyroliberin, Lopremone, Relefact
MOLECULAR FORMULA: C16H22N6O4
MOLECULAR WEIGHT: 362.39 g/mol
CAS NUMBER: 24305-27-9
PUBCHEM: CID 638678
TRH Thyrotropin (Protirelin) Research
TRH Thyrotropin (Protirelin) and Depression
The thyrotropin-releasing hormone has long been speculated to have anti-depressant effects. In an early study, doctors administered TRH Thyrotropin (Protirelin) directly into the spines of patients suffering from severe depression. The peptide showed a 50% or more reduction in the symptoms of depression and thoughts of suicide. The scientists report that “Administration of protirelin by an intrathecal route induced a rapid improvement in mood and suicidality in these refractory depressed patients, supporting the hypothesis that thyrotropin-releasing hormone could be a positive modulator of mood.” Researchers have speculated that the specific effects of TRH Thyrotropin (Protirelin) in depression may be related to a patient’s emotional state. Spinal administration of TRH Thyrotropin (Protirelin) is not convenient for treating depression. So studies aimed to determine its efficacy through IV. As it turns out, the peptide did not appear to cross the blood-brain barrier, making IV administration apparently as effective as intrathecal administration. Still, IV administration is impractical for most people. Hence the objective is to develop a version of TRH that can be administered via the intranasal route. Researchers speculate that this may be because nocturnal administration fits better with the natural circadian cycling of TRH. In the study, the percent of those subjects given TRH exhibited a 50% or greater reduction in symptoms of depression, which is in keeping with other studies. However, the effects lasted for up to 48 hours, far longer than the anti-depressant 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 Thyrotropin (Protirelin) and Motor Memory
Motor memory, also called muscle memory, refers to a form of procedural memory that develops through doing a specific motor task repeatedly. Research in mice without the gene for TRH Thyrotropin (Protirelin) have seemed to be slower to learn specific motor tasks, but that learning speed could be increased via exogenous administration of TRH. These findings lend support a long-held theory that TRH Thyrotropin (Protirelin) is active in the cerebellum and likely plays a role in facilitating motor learning. Knockout mice treated with TRH were observed to learn faster after four trials than untreated mice. This study suggests the peptide’s apparent ability to improve rates of motor learning. TRH and TRH analogs have been found to decrease ataxia in human cerebellar degenerative disease models. They appear to do so directly via their effect on motor learning and indirectly by increasing arousal and reducing the effects of depression.
TRH Thyrotropin (Protirelin) and Opioid Overdose
Opioids, such as Heroin and Oxycontin, can be deadly in the setting of overdose because they suppress the respiratory drive (urge to breath) in the brainstem. To date, the best available treatment for an opioid overdose is a substance called naloxone (Narcan). Narcan is highly effective but reverses not only the respiratory effects of opioids but also their pain-controlling effects. This can be a serious problem in people who suffer from chronic pain. Research studies examined the effects of the peptide when delivered intravenously or sprayed directly into the lungs, and TRH Thyrotropin (Protirelin) was observed to increase breathing rates in a dose-dependent manner without affecting pain control. The peptide appeared to prevent death in all the animals it was administered to. In addition, the two treatments (TRH and Narcan) 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 Thyrotropin (Protirelin) and 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 suggest that TRH can help improve mean arterial blood pressure and respiratory rate, similar to existing treatments for acute blood loss. In the study, TRH appeared to improve blood pH and prevent a decrease in arterial oxygen saturation, making it a potential adjuvant in treating blood loss and hypovolemic shock. Because of its apparent limited side effect profile, TRH may become a mainstay of emergency shock treatment in ambulances.
TRH Thyrotropin (Protirelin) and Disease Development
Changes in TRH levels are associated with thyroid disease. Still, researchers and doctors have observed that changes in TRH and other thyroid hormones also occur in various non-thyroid illnesses. Research in rats has suggested that specific neurons in the brain may be responsible for this phenomenon, as they lose the ability to produce TRH Thyrotropin (Protirelin) and respond to feedback mechanisms. There is interest in whether TRH supplementation may reduce the severity of non-thyroidal illness in some instances and act as an adjuvant to more directed therapies.
TRH Thyrotropin (Protirelin) and Aging
Research in mice has suggested that TRH protects certain organs against oxidative damage and natural aging. TRH Thyrotropin (Protirelin) appears to reduce 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), so researchers are interested in the ability of TRH to prevent amyloid buildup in the brain the same way that it may in the kidneys. Preliminary studies in mice have yielded unclear results. Researchers are unsure why TRH appears to increase arousal in aging mice, it isn’t clear if it has any impact on amyloid plaque buildup. The scientists reported that “This study suggests that high-dose TRH can be safely administered to AD patients and is neurobehaviorally active.” Research suggests that TRH levels drop in the hippocampus of patients suffering from AD, suggesting supplementation could help even if TRH has no impact on amyloid buildup in the brain. Experimental studies in TRH Thyrotropin (Protirelin) report that the peptide appears to exhibit minimal side effects and high oral and excellent subcutaneous bioavailability in mice. The dosage used in mice ( per kg) does not scale to humans.
- Marangell LB, George MS, Callahan AM, Ketter TA, Pazzaglia PJ, L’Herrou TA, Leverich GS, Post RM. Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients. Arch Gen Psychiatry. 1997 Mar;54(3):214-22. doi: 10.1001/archpsyc.1997.01830150034007. PMID: 9075462.
- Bunevicius R, Matulevicius V. Short-lasting behavioural effects of thyrotropin-releasing hormone in depressed women: results of placebo-controlled study. Psychoneuroendocrinology. 1993;18(5-6):445-9. doi: 10.1016/0306-4530(93)90019-h. PMID: 8416053.
- Callahan AM, Frye MA, Marangell LB, George MS, Ketter TA, L’Herrou T, Post RM. Comparative antidepressant effects of intravenous and intrathecal thyrotropin-releasing hormone: confounding effects of tolerance and implications for therapeutics. Biol Psychiatry. 1997 Feb 1;41(3):264-72. doi: 10.1016/s0006-3223(97)00372-7. PMID: 9024949.
- Watanave M, Matsuzaki Y, Nakajima Y, Ozawa A, Yamada M, Hirai H. Contribution of Thyrotropin-Releasing Hormone to Cerebellar Long-Term Depression and Motor Learning. Front Cell Neurosci. 2018 Dec 12;12:490. doi: 10.3389/fncel.2018.00490. PMID: 30618637; PMCID: PMC6299015.
- Boghosian JD, Luethy A, Cotten JF. Intravenous and Intratracheal Thyrotropin Releasing Hormone and Its Analog Taltirelin Reverse Opioid-Induced Respiratory Depression in Isoflurane Anesthetized Rats. J Pharmacol Exp Ther. 2018 Jul;366(1):105-112. doi: 10.1124/jpet.118.248377. Epub 2018 Apr 19. PMID: 29674333; PMCID: PMC5987997.
- Asai H, Watanabe Y, Yamauchi-Kohno R, Doi O. Reversal of hemorrhagic shock in rats using the metabolically stable thyrotropin-releasing hormone analog taltirelin hydrate. J Recept Signal Transduct Res. 2011 Dec;31(6):416-22. doi: 10.3109/10799893.2011.625427. Epub 2011 Nov 1. PMID: 22044177.
- Fliers E, Guldenaar SE, Wiersinga WM, Swaab DF. Decreased hypothalamic thyrotropin-releasing hormone gene expression in patients with nonthyroidal illness. J Clin Endocrinol Metab. 1997 Dec;82(12):4032-6. doi: 10.1210/jcem.82.12.4404. PMID: 9398708.
- Mellow AM, Sunderland T, Cohen RM, Lawlor BA, Hill JL, Newhouse PA, Cohen MR, Murphy DL. Acute effects of high-dose thyrotropin releasing hormone infusions in Alzheimer’s disease. Psychopharmacology (Berl). 1989;98(3):403-7. doi: 10.1007/BF00451695. PMID: 2501817.
Dr. Usman (BSc, MBBS, MaRCP) completed his studies in medicine at the Royal College of Physicians, London. He is an avid researcher with more than 30 publications in internationally recognized peer-reviewed journals. Dr. Usman has worked as a researcher and a medical consultant for reputable pharmaceutical companies such as Johnson & Johnson and Sanofi.
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