Thyrotropin-Releasing Hormone (TRH), Analogs and Related Peptides

Introduction

Thyrotropin-releasing hormone (TRH), also known as thyroid liberating hormone, is the first recognized hypothalamic release factor, but the peculiar N-(pyroGlu) and C-terminal (amide) residues delayed solving its TRH structure. TRH has been shown to be a broad biological response. In addition to regulating the central role of the pituitary-thyroid axis by mimicking the release of thyroid stimulating hormone, TRH has a considerable influence on the activity of many neurobiological systems. The development of selective and metabolically stable TRH analogues is an interesting area due to the potential of TRH to treat several central nervous system diseases. By modifying three amino acid residues, TRH analogs were synthesized, which improved their stability, potency, and showed different pharmacological effects from the parent peptide. Peptides with the structure pGlu-X-ProNH2, where X can be any amino acid residue, are collectively called TRH-like peptides.

Mechanism of action

The pharmacological effects of TRH can be roughly divided into endocrine effects and central nervous system (CNS) stimulation. TRH plays a key role in the regulation of HPT axis feedback to maintain thyroid homeostasis. TRH is a neuromodulator of several different neurotransmitters, including the most prominent dopamine, serotonin, acetylcholine, and opioids, which regulate the effects of many drugs that affect these neurotransmitters and other neurotransmitters. TRH is also likely to act as a neurotransmitter through a specific receptor that is widely distributed in the central nervous system and is rapidly cleared by specific catabolic pathways. Pharmacological studies have shown that TRH and its analogs can inhibit seizures induced by rat igniting and PTZ or glutamate.

Application of TRH and its analogs

The potential therapeutic application of TRH is not its endocrine effect, but rather its extensive stimulatory effects in the central nervous system. TRH and its analogs can counteract the inhibitory effects of drugs such as pentobarbital on the central nervous system. TRH and some of its analogs have been evaluated for beneficial effects in various shock states, cerebrovascular diseases, and spinal cord injuries. Recent studies, including the role of TRH in regulating the "steady state" of the nervous system, have also provided new avenues for the discovery of potent selective central nervous system activity TRH analogs. Clinically, TRH is effective in the treatment of intractable epilepsy such as infantile spasm, Lennox-Gaston syndrome, myoclonic seizures, and other extensive refractory partial epilepsy.

References

1. Monga, V., Meena, C. L., Kaur, N., & Jain, R. (2008). Chemistry and biology of thyrotropin-releasing hormone (TRH) and its analogs. Current medicinal chemistry, 15(26), 2718-2733.
2. Fr?hlich, E., & Wahl, R. (2018). The forgotten effects of thyrotropin-releasing hormone: metabolic functions and medical applications. Frontiers in neuroendocrinology.