Protirelin
Synthetic thyrotropin-releasing hormone: a three-amino-acid diagnostic once used to test the pituitary, and a long line of experiments beyond it
Protirelin is synthetic thyrotropin-releasing hormone (TRH), the tripeptide pGlu-His-Pro-NH2 with which the hypothalamus tells the pituitary to release thyroid-stimulating hormone and prolactin. Given intravenously, it was used to test that axis; FDA approved Thypinone in 1976 and Thyrel TRH in 1978, and both are now listed as discontinued. Researchers also tried it in depression, ALS and preterm lung disease, with mixed results.
What is it?
Thyrotropin-releasing hormone (TRH) is one of the smallest hormones: three amino acids, with a ring at one end and an amide at the other. The hypothalamus releases it to tell the pituitary to make thyroid-stimulating hormone (TSH) and prolactin. Synthetic TRH is called protirelin.
Its main medical use was diagnostic. An intravenous dose raises TSH, and the size of the rise separates problems in the thyroid from problems in the pituitary or hypothalamus. FDA approved Thypinone in 1976 and Thyrel TRH in 1978; both are now listed as discontinued, and sensitive TSH blood tests have replaced most uses of the stimulation test. It is still used in research and some clinics: a 2024 Korean study tested 952 people with subclinical hypothyroidism and found an exaggerated TSH response in 66%, more often as baseline TSH rose. A diagnostic 500 µg dose briefly raises blood pressure, by about 15 mm Hg in patients around heart surgery.
Because TRH also acts in the brain, it was tried as a treatment. Depressed patients show a blunted TSH response to it, and in a small crossover study five of eight people with refractory depression responded to an injection into the spinal fluid, with suicidality falling. In ALS, clinical studies were divided. None of these uses became an approved treatment.
The largest test was in pregnancy. Early trials suggested that adding TRH to steroids given before a preterm birth might mature the baby's lungs further, and a 1994 trial of 378 mothers reported fewer cases of respiratory distress. The Australian ACTOBAT trial then randomised 1,234 women and found the opposite: respiratory distress and need for ventilation were more common in TRH-exposed infants, and mothers had more nausea, vomiting, light-headedness and high blood pressure. A 2013 Cochrane review of 15 trials and over 4,600 women concluded that TRH added to steroids does not improve infant outcomes and causes maternal side effects; it increased the need for respiratory support and low Apgar scores.
Protirelin is not a supplement or a wellness product. Where it is still available, it is a diagnostic injection given under medical supervision.
Mechanism of Action
Protirelin is a copy of the hypothalamus's own signal to the pituitary, so what it does depends on how well the rest of the axis responds.
TRH receptor on the pituitary
It acts on pituitary cells that make TSH and prolactin, raising both; the size of the TSH rise is what the diagnostic test reads.
Thyroid axis
The TSH it releases stimulates the thyroid; a normal pituitary with a failing thyroid gives an exaggerated response, and pituitary disease gives a blunted one.
Brain effects
TRH also acts in the brain and spinal cord, which is why it was tried in depression and ALS; a diagnostic dose also briefly raises blood pressure, by mechanisms a 1984 study found did not involve catecholamines.
Crossing the placenta
Given to pregnant women, it transiently suppressed the infant's pituitary-thyroid axis, showing it reaches the fetus; the hope that this would mature the lungs was not borne out in large trials.
Published Research
These are studies of protirelin, read from their PubMed abstracts: its endocrine responses, the experimental treatments and its effect on blood pressure.
Dose-response in depression
Infused at 25, 100, 500 and 800 µg in 13 depressed patients and 12 controls, protirelin raised TSH and prolactin; depressed men had reduced TSH and prolactin responses at every dose, depressed women reduced TSH responses only.
Into the spinal fluid in refractory depression
In a double-blind crossover study, five of eight medication-free inpatients responded to 500 µg of intrathecal protirelin, with rapid reductions in depression scores and in suicidality.
Antenatal TRH with betamethasone
In 378 mothers expected to deliver at 24 to 32 weeks, adding TRH to betamethasone reduced respiratory distress syndrome from 52% to 31% among infants born 1 to 10 days after entry, and deaths from 14 to one.
Antenatal TRH: the meta-analysis
Across randomised trials, adding TRH to glucocorticoids did not reduce respiratory distress syndrome where surfactant was used; it transiently suppressed the infant's pituitary-thyroid axis and caused nausea, flushing, light-headedness and raised blood pressure in mothers.
Blood pressure after a diagnostic dose
In eight patients around heart surgery, 500 µg of intravenous protirelin transiently raised mean arterial pressure, from 88 to 103 mm Hg before surgery, by mechanisms not involving catecholamines.
ALS
Protirelin was suggested as an adjunct in ALS, but clinical studies were divided despite supportive experimental findings; the review points to sex differences in response.
ACTOBAT: antenatal TRH in 1,234 women
With glucocorticoids, 200 µg TRH every 12 hours (up to four doses) versus placebo increased infant respiratory distress (RR 1.17) and need for ventilation (RR 1.15), and raised maternal nausea, vomiting, light-headedness and blood pressure of 140/90 or higher; the authors concluded it cannot be recommended.
Cochrane review: 15 trials, over 4,600 women
Adding prenatal TRH to corticosteroids did not reduce death before discharge, respiratory distress (RR 1.05) or chronic lung disease (RR 1.01); it increased the need for respiratory support (RR 1.16) and low five-minute Apgar scores (RR 1.48), and maternal side effects.
The stimulation test in 952 people with subclinical hypothyroidism
An exaggerated TSH response (a rise of more than 25 mIU/L) occurred in 66%, more often at higher baseline TSH; positive thyroid antibodies were highly specific for an exaggerated response.
Dosing Data
Protirelin has no therapeutic dose. It was approved as a single intravenous diagnostic injection, and trials used other doses and routes for research.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the studies above.
Contraindications & Cautions
US products are discontinued. These cautions follow from the evidence.
Legal Status
Protirelin was once an approved US diagnostic.
Frequently Asked Questions
?What is protirelin used for?
It was used as a diagnostic: injected to see how the pituitary releases thyroid-stimulating hormone. Both US products are now discontinued.
?Is protirelin the same as TRH?
Yes. Protirelin is synthetic thyrotropin-releasing hormone, the tripeptide pGlu-His-Pro-NH2.
?Does TRH treat depression?
It has only been tested experimentally; five of eight patients responded to an injection into the spinal fluid in one small study. It is not an approved treatment.
?Does TRH help premature babies' lungs?
No. Large trials and a 2013 Cochrane review found no benefit when added to antenatal steroids, and more need for respiratory support in exposed infants.
?Is the TRH test still used?
Rarely in routine care, because sensitive TSH tests answer most questions, but it is still used in research and some clinics, for example in subclinical hypothyroidism.
References
- [fda] FDA. Drugs@FDA (openFDA): Thypinone NDA 017638 (November 5, 1976) and Thyrel TRH NDA 018087 (July 18, 1978), both discontinued. Read September 30, 2026.
- [other] European Medicines Agency. Medicines register: no entry for protirelin. Read September 30, 2026.
- [pubmed] Garbutt JC, et al. "Dose-response studies with protirelin." Arch Gen Psychiatry, 1994;51(11):875-83. PMID: 7944876.
- [pubmed] Marangell LB, et al. "Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients." Arch Gen Psychiatry, 1997;54(3):214-22. PMID: 9075462.
- [pubmed] Knight DB, et al. "A randomized, controlled trial of antepartum thyrotropin-releasing hormone and betamethasone in the prevention of respiratory disease in preterm infants." Am J Obstet Gynecol, 1994;171(1):11-6. PMID: 8030684.
- [pubmed] Gross I, et al. "Is there a role for antenatal TRH therapy for the prevention of neonatal lung disease?." Semin Perinatol, 2001;25(6):406-16. PMID: 11778911.
- [pubmed] Zaloga GP, et al. "Diagnostic dosages of protirelin (TRH) elevate BP by noncatecholamine mechanisms." Arch Intern Med, 1984;144(6):1149-52. PMID: 6428340.
- [pubmed] Miller SC, et al. "Protirelin (thyrotropin-releasing hormone) in amyotrophic lateral sclerosis. The role of androgens." Arch Neurol, 1989;46(3):330-5. PMID: 2563937.
- [pubmed] "Australian collaborative trial of antenatal thyrotropin-releasing hormone (ACTOBAT) for prevention of neonatal respiratory disease." Lancet, 1995;345(8954):877-82. PMID: 7707809.
- [pubmed] Crowther CA, et al. "Thyrotropin-releasing hormone added to corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease." Cochrane Database Syst Rev, 2013;2013(11):CD000019. PMID: 24265169.
- [pubmed] Yoo MH, et al. "Role of Thyrotropin-Releasing Hormone Stimulation Test and Autoantibody in 952 Subjects with Subclinical Hypothyroidism." J Endocr Soc, 2024;9(1):bvae212. PMID: 39749109.
Sources & Citations
Every study on this page was read from its PubMed record. Regulatory status comes from FDA's Drugs@FDA database and EMA's register, read September 30, 2026. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.