Distinct sequence of gonadotropin-releasing hormone (GnRH) in dogfish brain provides insight into GnRH evolution

In vertebrates, gonadotropin-releasing hormone (GnRH) belongs to a family of decapeptides characterized by the conservation of residues 1, 2, 4, 9, and 10. In the jawed vertebrates only positions 5, 7, and 8 in the GnRH molecules vary. We have now purified two forms of GnRH from the brains of spiny dogfish (Squalus acanthias) by using reverse-phase high-performance liquid chromatography. The primary structures were established by automated Edman degradation and mass spectral analysis. The distinct structure of the first form (dogfish GnRH) is pGlu-His-Trp-Ser-His-Gly-Trp-Leu-Pro-Gly-NH2 (pGlu represents pyroglutamyl). The second peptide is identical to a form of GnRH originally isolated from chicken brains (chicken GnRH-II; pGlu-His-Trp-Ser-His-Gly-Trp-Tyr- Pro-Gly-NH2) and is widespread throughout the vertebrates. We are aware of no other species of cartilaginous fish in which the primary structures of two forms of GnRH have been determined. The presence of chicken GnRH-II in dogfish supports the idea that chicken GnRH-II is the oldest GnRH to evolve in jawed vertebrates. With the addition of the dogfish GnRH structure to the family, two main structural branches of GnRH can be delineated. The physiological effects of dogfish GnRH included the release of not only gonadotropin but also growth hormone from goldfish pituitary fragments.