Gonadotropin-releasing hormone type II receptor (GnRHR2)

The **Gonadotropin-releasing hormone type II receptor** (GnRHR2) is a member of the rhodopsin-like family of class A G protein-coupled receptors (GPCRs) that specifically binds the evolutionarily conserved neuropeptide GnRH II, found from fish to humans[5]. The receptor typically consists of seven transmembrane domains with a prominent cytoplasmic C-terminal tail, which contrasts with the tailless type I GnRH receptor[3][5]. GnRHR2 is primarily involved in regulating reproductive functions, encompassing steroid hormone synthesis and neuromodulatory actions that may include regulation of sexual behavior and gonadotropin secretion[3][5]. **Key issue:** In humans, the GNRHR2 gene (encoding the type II receptor) contains disabling mutations, and evidence strongly suggests that a functional protein is not produced[4][6][7]. Studies have detected only a non-functional pseudogene in humans, unlike in many other mammals or non-mammalian vertebrates where the receptor is functional[4][6][7]. Thus, while GnRHR2 acts as a bona fide therapeutic target in some species, its relevance as a target in humans is questionable, and currently, it is not considered a therapeutically actionable target in humans[6][7]. In summary, while **GnRHR2 is a GPCR important in reproductive regulation in many animals**, it is most likely nonfunctional in humans due to an inactivating gene mutation and is *not* a validated drug target in clinical medicine[4][6][7]. Drugs targeting GnRH II receptors (such as peptide agonists) have shown biological activity in non-human systems, but not in humans.

Other names

GnRH type II receptorGonadotropin-releasing hormone receptor 2GNRHR2GnRH-II receptor

Activation of Gαq/11 dependent signaling pathways; Activation of protein kinases (e.g., ERK1/2, p38 MAP kinase)