Primary structure of gonadotropin-releasing hormone from lamprey brain.

The primary structure of gonadotropin-releasing hormone (GnRH) isolated from whole brains of lamprey is pGlu-His-Tyr-Ser-Leu-Glu-Trp-Lys-Pro-Gly-NH2. This unique decapeptide was isolated and purified from brain extracts by reverse-phase high performance liquid chromatography. The structure of the peptide was established from chymotryptic fragments that were identified by protein sequence analysis and fast atom bombardment mass spectrometry. The peptide reacts with an antiserum raised against mammalian GnRH and is structurally identified as a member of the GnRH family by the amino and carboxyl termini of pGlu1-His2 and Pro9-Gly10NH2, the conservation of Ser4 in the internal segment of the molecule and its length of 10 amino acids. For the first time, amino acid substitutions are found in positions 3 and 6, critical for biological potency and conformation, respectively. Additionally, a second form of GnRH (lamprey II GnRH), representing about 10% of the total GnRH immunoreactive material in the brain, was isolated; its amino acid composition differs by 3 residues from lamprey I GnRH. Synthetic lamprey I GnRH elevates plasma estradiol in adult female lampreys.