Primary structure and biological activity of a third gonadotropin-releasing hormone from lamprey brain.

Previous studies have led to the identification of two molecular forms of GnRH (GnRH-I and II) in the brain of the sea lamprey, Petromyzon marinus. From analysis of these two forms, the primary structure of GnRH-I and the amino acid composition of GnRH-II were determined. We have now isolated a third molecular form of GnRH (GnRH-III) from the brain of this species that is different from GnRH-I and -II. The primary structure of GnRH-III is pGlu-His-Trp-Ser-His-Asp-Trp-Lys- Pro-Gly-NH2. A synthetic decapeptide with this amino acid sequence was chromatographically identical to natural GnRH-III. Intraperitoneal injection of synthetic lamprey GnRH-III (0.1 microgram/g) produced a significant (P < 0.05) elevation of plasma progesterone (31% over basal values) in female lampreys that was comparable to that produced by the same dose of lamprey GnRH-I (36% over basal). The elevation in plasma estradiol produced by lamprey GnRH-III (244% over basal) was significantly (P < 0.05) less than the elevation produced by GnRH-I (322% over basal). We propose based on the biological activity of lamprey GnRH-III in these studies and the occurrence of this peptide during metamorphosis in lampreys, that both lamprey GnRH-I and -III are neurohormones involved in reproduction in lampreys.