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

The Gonadotropin-releasing hormone II receptor (GnRHR2) is a G protein-coupled receptor that specifically recognizes GnRH-II, a highly conserved decapeptide found across vertebrate species [1][2]. While the GnRH-I receptor is the primary regulator of the hypothalamic-pituitary-gonadal axis, GnRHR2 is involved in extra-pituitary functions, including the regulation of reproductive behavior and the inhibition of cell proliferation in reproductive tissues [2][3]. In humans, the GNRHR2 gene is frequently characterized as a pseudogene due to a frame-shift mutation and a premature stop codon, although some evidence suggests the existence of functional transcripts or truncated isoforms in specific tissues [4][5]. In non-human primates and other vertebrates, GnRHR2 is fully functional and signals primarily through the Gq/11 pathway [2]. The receptor has gained attention as a potential target in oncology, particularly for ovarian and endometrial cancers, where GnRH-II analogs have demonstrated anti-proliferative effects [3][6]. Therapeutic development is complicated by the need for selectivity to avoid cross-activation of the GnRH-I receptor, which would trigger systemic hormonal changes [5].

Other names

Type II GnRH receptorGNRHR2GnRH receptor 2Gonadotropin-releasing hormone receptor 2

The Gonadotropin-releasing hormone II receptor (GnRHR2) functions as a G protein-coupled receptor that, upon activation by its ligand GnRH-II, primarily engages the Gq/11 signaling pathway. This activation stimulates phospholipase C, leading to the generation of inositol trisphosphate and diacylglycerol, which subsequently increases intracellular calcium concentrations and activates protein kinase C [1][2]. In certain cellular contexts, particularly in cancer cells, this signaling cascade is associated with the activation of antiproliferative and pro-apoptotic pathways [3][6].