What is TRH Thyrotropin (Protirelin)?
Thyrotropin Releasing Hormone (TRH), often called Protirelin, is a small peptide hormone synthesized in the hypothalamus. Its primary functions are 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 has anti-depressant and anti-suicidal properties and plays a role in regulating the aging process, arousal, feeding behavior, 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 and Depression
The thyrotropin-releasing hormone has long been speculated to have anti-depressant effects. In an early study, doctors administered 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. Researchers have speculated that the specific effects of Protirelin in depression may be related to a patient’s emotional state.
Spinal administration of Protirelin is not convenient for treating depression. So studies aimed to determine its efficacy through IV. As it turns out, the peptide does cross the blood-brain barrier, and IV administration is just 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 size percent of those given TRH showed 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 Research 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 Protirelin has shown to be 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 Protirelin 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 than untreated mice. This shows improved 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 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 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.
When given intravenously or sprayed directly into the lungs, Protirelin boosted breathing rates in a dose-dependent manner without affecting pain control. The peptide prevented death in all 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 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 improve mean arterial blood pressure and respiratory rate, similar to existing treatments for acute blood loss. TRH also improved blood pH and prevented a decrease in arterial oxygen saturation, making it a useful adjuvant in treating 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
Changes in TRH levels are associated with thyroid disease. Still, researchers and doctors have also observed that changes in TRH and other thyroid hormones also occur in various 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 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 May Affect the Aging Process
Research in mice has shown that TRH protects certain organs against oxidative damage and natural aging. Protirelin 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). 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. 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.
Protirelin exhibits minimal side effects and high oral and excellent subcutaneous bioavailability in mice. The dosage used in mice ( per kg) does not scale to humans.