GnRH-I is a small 10 amino acid long peptide (decapeptide) from the hypothalamus,It is also known as luteinizing hormone releasing hormone (LHRH), is a key molecule in the regulation of reproduction in vertebrates. GnRH, a decapeptide, is produced by neur
GnRH III, an evolutionarily conserved member of the GnRH family, can stimulate the secretion of gonadotropins, it stimulates the secretion of both luteinizing and follicle-stimulating hormones.
NBI-42902 is a potent inhibitor of peptide radioligand binding to the human GnRH receptor (K(i) = 0.56 nm). Tritiated NBI-42902 binds with high affinity (K(d) = 0.19 nm) to a single class of binding sites and can be displaced by a range of peptide and nonpeptide GnRH receptor ligands. In vitro experiments demonstrate that NBI-42902 is a potent functional, competitive antagonist of GnRH stimulated IP accumulation, Ca(2+) flux, and ERK1 2 activation. It did not stimulate histamine release from rat peritoneal mast cells. Finally, it is effective in lowering serum LH in castrated male macaques after oral administration. Overall, these data provide a benchmark of pharmacological characteristics required for a nonpeptide GnRH antagonist to effectively suppress gonadotropins in humans and suggest that NBI-42902 may have clinical utility as an oral agent for suppression of the hypothalamic-pituitary-gonadal axis. (source: Endocrinology. 2007 Feb;148(2):857-67. Epub 2006 Nov 9.)