Gonadotropin-releasing hormone receptor II (GnRHR2) (GnRHR2)

The Gonadotropin-releasing hormone receptor II (GnRHR2) is a G protein-coupled receptor that selectively binds the GnRH-II isoform (His5, Trp7, Tyr8-GnRH), a decapeptide that is evolutionarily older and more conserved than GnRH-I (UniProt: Q96P88; PMID: 11443215). While GnRHR1 is the central regulator of the hypothalamic-pituitary-gonadal axis, GnRHR2 is involved in extra-pituitary functions, including the modulation of reproductive behavior and the regulation of cell proliferation in peripheral tissues (PMID: 12533512). In humans, the GNRHR2 gene is frequently classified as a pseudogene due to a frame-shift and premature stop codon, but functional transcripts and protein expression have been detected in various tissues, including the brain, placenta, and certain cancer cells (NCBI Gene ID: 114814; PMID: 15695336). Unlike the human GnRHR1, which lacks a C-terminal tail, GnRHR2 typically possesses this domain, allowing for rapid desensitization and internalization upon ligand binding (PMID: 11861507). The receptor's role in oncology is of particular interest, as GnRH-II analogs have demonstrated anti-proliferative effects in breast, ovarian, and endometrial cancer cell lines, often mediated through GnRHR2-specific pathways (PMID: 17068134). Consequently, GnRHR2 represents a potential therapeutic target for non-hormonal cancer treatments and reproductive disorders, though its status as a functional target in all humans remains a subject of scientific debate.

Other names

GnRH receptor type 2GNRHR2Type II GnRH receptorGonadotropin-releasing hormone receptor 2

Agonist binding to GnRHR2 triggers the Gq/11 signaling cascade, activating phospholipase C and increasing intracellular calcium levels, which subsequently modulates downstream effectors like MAPK/ERK to influence cell growth and behavior (PMID: 12533512).