Discontinued Growth Hormone Axis

Protirelin

also known as: TRH, thyrotropin-releasing hormone, Thypinone, Relefact TRH, Thyrel TRH

Synthetic TRH (thyrotropin-releasing hormone) — historically FDA-approved in the US as Thypinone, Relefact TRH, and Thyrel TRH for TSH stimulation testing; US commercial supply has lapsed and TRH testing is now rarely performed with the widespread availability of sensitive third-generation TSH assays.

Synthetic thyrotropin-releasing hormone (TRH) — a pyroglutamyl-histidyl-prolinamide tripeptide that binds the TRH receptor on pituitary thyrotrophs and lactotrophs, stimulating TSH and prolactin release. Historically used as a diagnostic agent for TSH stimulation testing (assessment of secondary hypothyroidism, pituitary reserve, and atypical hyperthyroidism) and, much more rarely, for prolactin reserve testing. US commercial supply of protirelin (Thypinone / Relefact TRH / Thyrel TRH) has lapsed, and TRH testing has largely been replaced by sensitive third-generation TSH immunoassays. Remains available in some other markets. Included for reference as a canonical hypothalamic releasing peptide.

Mechanism of action

Binds TRH receptor (TRHR) — a Gq-coupled receptor — on pituitary thyrotrophs to stimulate TSH release, and on lactotrophs to stimulate prolactin release. Effects are prompt (peak TSH at 20–30 minutes) and dose-dependent. In central (secondary) hypothyroidism, TSH response to TRH is blunted; in primary hypothyroidism, response is exaggerated.

Primary uses

Historical: TSH stimulation testing for secondary hypothyroidism and pituitary reserve
Historical: prolactin reserve testing

Typical dosing

200–500 mcg single diagnostic dose (intravenous bolus)

Historical adult diagnostic dose 500 mcg IV; serial TSH and prolactin sampling at 15, 30, and 60 minutes post-dose.

Regulatory status

Historical FDA approvals (Thypinone, Relefact TRH, Thyrel TRH) for TSH stimulation testing. US commercial supply not currently available; the agent was withdrawn commercially rather than for safety reasons. Available in some non-US markets.

References

[fda-pi] Thyrel TRH / Relefact TRH (protirelin) historical Prescribing Information. (US commercial supply not currently available.)
[review] Spencer CA, et al. "Clinical utility of sensitive TSH assays in thyroid disease diagnosis and management." Thyroid, 1990;1:21-38 (historical context for TRH test obsolescence).

Related peptides

Corticorelin

Ferring Pharmaceuticals' synthetic ovine CRH (Acthrel) — FDA-approved diagnostic peptide used to distinguish pituitary Cushing disease from ectopic ACTH secretion via inferior petrosal sinus sampling or peripheral ACTH/cortisol response testing.

Gonadorelin

The native GnRH decapeptide — the hypothalamic signal that drives LH/FSH release and downstream testosterone/estradiol production. Historically FDA-approved (Factrel, Lutrepulse), now widely used in TRT-adjacent fertility protocols as a testicular-preservation alternative to HCG.

Sermorelin

The N-terminal 29 amino acids of native GHRH — a former FDA-approved diagnostic and pediatric GH-deficiency therapy, now widely compounded for adult anti-aging protocols.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.