Thyrotropin-releasing hormone receptor 1 (TRHR1)

Thyrotropin-releasing hormone receptor 1 (TRHR1) is a Class A G protein-coupled receptor that serves as the primary mediator for the actions of thyrotropin-releasing hormone (TRH). It is predominantly expressed in the anterior pituitary gland and throughout the central nervous system, including the hypothalamus, brainstem, and spinal cord. In the pituitary, TRHR1 activation stimulates the release of thyroid-stimulating hormone (TSH) and prolactin, thereby playing a central role in the hypothalamic-pituitary-thyroid axis and metabolic regulation. Beyond its endocrine functions, TRHR1 acts as a neuromodulator in the brain, influencing arousal, motor control, and thermogenesis. Clinically, TRHR1 is targeted by agonists like protirelin for diagnostic thyroid testing and by synthetic analogs such as taltirelin for the treatment of neurodegenerative disorders like spinocerebellar ataxia. The receptor is also being investigated for its potential neuroprotective roles in spinal cord injury and various psychiatric conditions.

Other names

TRH-RTRHRThyroliberin receptorTRH receptor type 1Thyrotropin-releasing hormone receptor

Agonism of the TRHR1 receptor activates the Gq/11-phospholipase C (PLC) signaling pathway, leading to the production of inositol trisphosphate (IP3) and diacylglycerol (DAG). This cascade triggers the release of intracellular calcium and activation of protein kinase C (PKC), which in the pituitary stimulates the secretion of thyroid-stimulating hormone (TSH) and prolactin. In the central nervous system, this activation modulates neurotransmitter release and provides neuroprotective effects.