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Three Forms of Gonadotropin-Releasing Hormone, Including a Novel Form, in a Basal Salmonid, Coregonus clupeaformis¹

^a Department of Biology, University of Victoria, Victoria, British Columbia, Canada V8W 3N5 ^b The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037

Multiple forms of GnRH within individual brains may have different functions. However, some vertebrates such as salmonids continue to reproduce even though they have lost or do not express 1 of the 3 forms of GnRH found in most other teleosts. We examined a basal salmonid, lake whitefish, to determine the mechanism by which a reduction in the number of GnRH forms occurs. We identified for the first time 3 distinct GnRHs in a salmonid. One form is novel and is designated whitefish GnRH. The primary structure is pGlu-His-Trp-Ser-Tyr-Gly-Met-Asn-Pro-Gly-NH₂. HPLC and RIA were used for purification followed by Edman degradation for sequence determination. Mass spectroscopy was used to confirm the sequence and amidation of the peptide. The other 2 forms, salmon GnRH and chicken GnRH-II, are identical to the 2 forms found in salmon, which evolved later than whitefish. Synthetic whitefish GnRH is biologically active, as it increased mRNA expression of growth hormone and the -subunit for LH and thyroid-stimulating hormone in dispersed fish pituitary cells. Our data support the hypothesis that the ancestral salmonid had a third GnRH form when the genome doubled (tetraploidization), but the third form was lost later in some salmonids due to chromosomal rearrangements. We suggest that the salmon GnRH form compensated for the loss of the third form.

First decision: 31 December 2001.

¹ This work was funded by grants from the Canadian Institutes of Health Research, the Natural Science and Engineering Research Council, NIH (grant HD 13527 and a Shared Equipment Grant 1 S10 RR15843-01), and the Foundation for Medical Research.

² Correspondence. FAX: 250 721 7120; nsherwoo{at}uvic.ca

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