EstablishedHuman trials

Thyroid Releasing Hormone

Thyrotropin-Releasing Hormone (TRH)

Overview

Thyrotropin-Releasing Hormone (TRH) is a tripeptide (pyroglutamyl-histidyl-proline amide) produced by the hypothalamus that stimulates the pituitary to release thyroid-stimulating hormone (TSH) which in turn stimulates thyroid hormone production. Beyond its role in the hypothalamic-pituitary-thyroid axis TRH has demonstrated potent central nervous system effects including antidepressant activity stimulant effects and neuroprotective properties. It is used diagnostically to test pituitary and thyroid function and is being investigated for depression amyotrophic lateral sclerosis and spinal cord injury.

Mechanism of Action

TRH acts through TRH receptors (TRH-R1 and TRH-R2) coupled to Gq proteins expressed in the pituitary thyroid and throughout the brain. Pituitary TRH receptor activation stimulates both TSH and prolactin release. In the brain TRH receptors are found in limbic regions brainstem and spinal cord where TRH acts as a neuromodulator independent of its endocrine functions. Central TRH signaling has antidepressant effects — it activates monoaminergic systems increasing dopamine serotonin and norepinephrine activity. TRH also has direct neurotropic effects promoting motor neuron survival and has shown benefit in clinical trials for ALS. It antagonizes barbiturate and ethanol-induced CNS depression explaining early research interest in its analeptic (arousal-promoting) properties. The combination of thyroid axis activation and direct CNS effects makes TRH a pleiotropic neurohormone with multiple therapeutic angles.

Where does Thyroid Releasing Hormone sit?

See how this peptide compares across all 85 peptides in our database.

Dosage Information

Typical Dose

0.5-1 mg (diagnostic use), various research doses

Frequency

Single dose for diagnostic testing

Administration

Intravenous (diagnostic), intranasal (research)

Notes

Intranasal TRH is being investigated for depression and neuroprotection as a route that avoids rapid systemic metabolism. Very short half-life (5-6 minutes IV) necessitates intranasal or sustained-release formulations for therapeutic use.

Potential Side Effects

Nausea (common with IV administration)Flushing (common)Urge to urinate (common, transient)Mild blood pressure changes (uncommon)Metallic taste (uncommon)

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Quick Facts

Administration
Intravenous (diagnostic), intranasal (research)
Typical Dose
0.5-1 mg (diagnostic use), various research doses
Frequency
Single dose for diagnostic testing
References
0 curated + 45 from PubMed
Clinical Trials
22 registered
Evidence Score
62.0 / 100