Thyrotropin 25mg


Size: 25mg
Contents: Thyrotropin (25mg)
Form: Lyophilized powder
Purity: >99%
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Thyrotropin – the Neuromodulator Peptide Hormone

Thyroid hormones that are produced naturally in the body are well known for regulating several bodily functions including growth and metabolism. In order to maintain the synchrony of these regulating mechanisms and hemostasis in the body, hormones are released by the hypothalamus called Thyrotropin releasing hormone (TRH)(1).

The main function of Thyrotropin releasing hormone (TRH) is to maintain the levels of thyroid hormones. If the levels of these hormones decrease, the body would naturally secrete more TRH to stimulate the thyroid gland and secrete more thyroid hormones. If the levels of thyroid hormone are significantly high, the body will secrete less TRH to reduce the production of these thyroid hormones (2).

While TRH is an endogenous compound, there is a pharmaceutical peptide form available, which simulates TRH characteristics, known as Protirelin (3).

What is Protirelin?

Protirelin is the synthetic analogue of the endogenous peptide hormone Thyrotropin releasing hormone (3).

Analogous to TRH, Protirelin is a tripeptide composed of three amino acid residues connected in a sequential form (3).

As with most of the peptides, Protirelin is a highly stable and biocompatible compound with minimal side effects and high stability in the body.

Discovery Timelines

Touted as one of the landmark discoveries of the 20th century, TRH discook place in 1969 by two of the well-known scientists who later shared a Nobel Prize for the same (4).

Isolated from the pig or sheep hypothalamus, Thyrotropin was the smallest known molecule amongst the peptides (5). Various research and synthetic analogues of the peptide have since been developed and explored, one of them being Protirelin.

How Does Protirelin Function?

Protirelin primarily functions via binding to the thyrotropin releasing hormone (TRH) receptors TRH-1 and TRH-2 (6).

On binding with these receptors, which are mediated by G proteins, a cascade of signals is generated. First, a hydrolase enzyme is activated, which in turns causes a breakdown of an existing compound and produces inositol. Inositol then binds with another receptor, which is a calcium channel, resulting in increased cellular levels of calcium.

This increased level of calcium thereby activates protein kinase C leads to elevated phosphorylation of secondary messenger enzymes.

All these signals collectively modify the gene expression in the nucleus of the cell, which then transduces this TRH binding signal into a body message and stimulates the thyroid gland to increase or decrease thyroid hormone production, depending on the levels of thyroid hormones in the body.

What Are the Health Benefits of Thyrotropin?

The main advantage of Thyrotropin, aka Protirelin, is that it is used as a diagnostic tool to determine the functioning levels of the anterior pituitary and hypothalamus gland. This not only helps diagnose any underlying body conditions but also helps to determine if any adjustments need to be made to any thyroid hormone dose being administered.

The other use of Thyrotropin is that it can be used to treat depression and suicidal thoughts, mostly when administered via intrathecal route of administration.

Studies are ongoing to determine the potential use of the peptide in managing various disorders of the central nervous system. Thyrotropin is also believed to play a fundamental role in managing the metabolic and hormonal functions in the body.

Research and Clinical Studies

Adjunct Therapeutic Role to Treat ALS

Amyotrophic Lateral Sclerosis (ALS) is an extremely rare neurological disorder that impacts the functioning of voluntary muscle movements, including chewing, talking, and walking, by adversely impacting the nerve cells (7).

ALS is a progressive ailment where the symptoms worsen over time. Currently, there is no cure or effective treatment for this ailment (7).

Researchers are still trying to figure out the effectiveness of Thyrotropin in ALS treatment. Thyrotropin is believed to act as a neuromodulator during the hyperactivity of the hypothalamic nervous system, and this is why it is suggested to be used as an adjunct therapeutic compound in treating ALS (8). While there is convincing data that suggests the potential effectiveness of Thyrotropin in ALS, this area is yet to be fully examined.

Role in Depression Treatment

Initial clinical studies conducted to assess the therapeutic effects of the peptide were hindered because the peptide is unable to cross the blood brain barrier in humans (9). The blood brain barrier is one of the most difficult membranes to cross as it is composed of closely spaced cells in order to prevent toxic substances from crossing over and reaching the brain (10).

Consequently, in this study (9), the peptide was administered via the intrathecal route i.e., administration into the spinal theca (or cerebrospinal fluid).

Eight patients suffering from depression, who were not on any medications, were administered with 500 microg of peptide via intrathecal route followed by a sham injection administration after one week, in a double-blind clinical trial study.

Upon analysis, it was noted that five out of the eight patients showed a 50% or more reduction in depressive and suicidal thoughts. These responses were quick, though short lived. These results indicated that Thyrotropin might potentially be used as a therapeutic agent to treat depression.

Role as a Therapeutic Diagnostic Tool

In this study (11), 44 consecutive patients of a psychiatric hospital were subjected to the Protirelin test. All these patients were referred to the psychiatric hospital for the treatment of depression and lack of energy.

Out of the 44 patients, 19 showed a blunted response to the test, indicating hypothyroidism, whereas 6 showed significantly higher response to the test. Five of these patients with a high augmented response had naturally produced antithyroid antibodies in their body.

These results suggest that the peptide is a promising candidate to be used to diagnose improper functioning of thyroid gland as well as determine if the patient is suffering from depression.

Effect of Diagnostic Doses of Thyrotropin

While conducting diagnostic tests on volunteers, it was noticed that the peptide caused an elevation in the blood pressure rate.

In this study (12), eight patients were examined one day before, the day after, and four weeks after their heart surgery. All these patients were administered with 500 micrograms of Thyrotropin.

While peptide administration did not cause any significant changes in the levels of heart rate and thyroid hormones, the blood pressure rates increased on all three days. These results indicate that Thyrotropin administration leads to increased blood pressure rates, and hence it is important for the clinical practitioner to be aware of the patient’s pre-existing heart conditions when it comes to peptide administration.

Side Effects Caused by Thyrotropin

The known side effects associated with the intravenous administration of the peptide include nausea, vomiting, flushing, and an urgency to urinate (13). Moreover, reports have shown that intravenous administration of thyrotropin may also cause some significant changes to the blood pressure rate (13).

When administered via intrathecal route, the peptide has been shown to cause shivering, sweating, restlessness, and increased blood pressure.

Peptide Drug Profile – Pharmacokinetics & Pharmacodynamics

16 volunteers with healthy functioning of thyroid gland were subjected to different doses of Thyrotropin in this study (14), including 200 microg via intravenous route, 2 mg via nasal, and 40 mg via oral administration.

The peak levels of Thyrotropin releasing hormones were achieved within 2 minutes after intravenous administration, 10 minutes after nasal and 150 minutes post oral administration. This suggested that the half-life of the TRH was approximately 7 minutes, 22 minutes, and 31 minutes for the respective three routes of administration.

In terms of pharmacodynamics, the highest levels of Thyrotropin stimulating hormone (TSH) occurred 30 min post peak TRH concentration for all three routes of administration. This result indicated that the secretion of TSH is dependent on the TRH concentrations in blood.

Dose Response Studies

Patients suffering from major depression show reduced TSH response toward Thyrotropin releasing hormone treatment. It is believed that this is because, during depression, the pituitary TRH receptors are downregulated.

In this study (15), 13 depression patients (7 female, 6 male) were subjected to increasing doses of 25, 100, 500, and 800 microg of Protirelin for 3 to 7 days. The TSH responses were monitored throughout the study.

Upon examination, it was noticed that the male patients showed consistently reduced levels of TSH, as well as prolactin, upon this treatment for all four doses. While in women, the levels of TSH reduced significantly, with no impact to the levels of prolactin.

While the results in women remain unclear, the outcomes in men validate the hypothesis that the TRH receptors are downregulated in depression.


Thyrotropin is an endogenous tripeptide compound secreted by the hypothalamus gland. The synthetic analogue of Thyrotropin is called Protirelin, sold under the brand name of Thyrel TRH.

Thyrotropin mainly helps in regulating the levels of thyroid hormones (T3 and T4) in the body. It plays the role of the neuromodulator via binding with the Thyrotropin releasing hormone receptors and inducing a cascade of signals in the nervous system.

Research has shown promising results of the peptide in the treatment of depression and suicidal thoughts. Additional studies are going on to date to fully explore this peptide to ensure we use this compound to its fullest potential in treating various biological diseases.


1. Shahid MA, Ashraf MA, Sharma S. Physiology, Thyroid Hormone. [Updated 2021 May 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021.

2. Michigan Medicine, University of Michigan Health. March 31, 2020.

3. National Center for Biotechnology Information. “PubChem Compound Summary for CID 638678, Protirelin” PubChem,

4. Boler J, Enzmann F, Folkers K, Bowers CY, Schally AV. The identity of chemical and hormonal properties of the thyrotropin releasing hormone and pyroglutamyl-histidyl-proline amide. Biochem Biophys Res Commun. 1969 Nov 6;37(4):705-10.

5. Kobayashi, Naotake et al. “Discovery of the Orally Effective Thyrotropin-Releasing Hormone Mimetic: 1-{N-[(4S,5S)-(5-Methyl-2-oxooxazolidine-4-yl)carbonyl]-3-(thiazol-4-yl)-l-alanyl}-(2R)-2-methylpyrrolidine Trihydrate (Rovatirelin Hydrate).” ACS omega vol. 3,10 (2018): 13647-13666.

6. A. Eugene Pekary, Protirelin should be used with care in patients with ischemic heart disease, obstructive airway disease, or severe hypopituitarism (Parfitt, 1999).

7. Amyotrophic Lateral Sclerosis (ALS) Fact Sheet. National Institute of Neurological Disorders and Stroke.

8. Miller SC, Warnick JE. Protirelin (thyrotropin-releasing hormone) in amyotrophic lateral sclerosis. The role of androgens. Arch Neurol. 1989 Mar;46(3):330-5.

9. 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.

10. Blood-brain barrier.

11. Sternbach HA, Gold MS, Pottash AC, Extein I. Thyroid failure and protirelin(thyrotropin-releasing hormone) test abnormalities in depressed outpatients. JAMA. 1983 Mar 25.

12. Zaloga GP, Chernow B, Zajtchuk R, Chin R, Rainey TG, Lake CR. Diagnostic dosages of protirelin (TRH) elevate BP by noncatecholamine mechanisms. Arch Intern.

13. Borowski GD, Garofano CD, Rose LI, Levy RA. Blood pressure response to thyrotropin-releasing hormone in euthyroid subjects. J Clin Endocrinol Metab. 1984 Jan;58(1):197-200.

14. Duntas L, Keck FS, Loos U, Pfeiffer EF. Pharmakokinetik und Pharmakodynamik von Protirelin (TRH) beim Menschen [Pharmacokinetics and pharmacodynamics of protirelin (TRH) in man]. Dtsch Med Wochenschr. 1988 Sep 2;113(35):1354-7. German.

15. Garbutt JC, Mayo JP, Little KY, Gillette GM, Mason GA, Dew B, Prange AJ Jr. Dose-response studies with protirelin. Arch Gen Psychiatry. 1994 Nov;51(11):875-83.


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