A 2ND GENE FOR GONADOTROPIN-RELEASING-HORMONE - CDNA AND EXPRESSION PATTERN IN THE BRAIN

In vertebrates, the gonadotropin-releasing hormone (GnRH) decapeptide is secreted from hypothalamic nerve terminals to regulate reproduction via control of synthesis and release of pituitary gonadotropins. Only one GnRH peptide has been found in mammals, with one exception, altho ugh numerous other vertebrate species express more than one of the eig ht known decapeptide forms as shown by immunocytochemical labeling of distinct cell groups in the brain. However, neither the functional nor the evolutionary relationships among these GnRH forms are clear, beca use only one preprohormone gene sequence from any species has been rep orted. The most ubiquitous alternative form of GnRH is [His(5),Trp(7), Tyr(8)]GnRH (also referred to as chicken-II), which differs from the m ammalian sequence at amino acids 5, 7, and 8. This peptide has been sh own to have the most potent releasing-hormone activity, although immun ocytochemical staining has suggested it is synthesized only in the mes encephalon. Here we report the cloning and expression pattern of the g ene for the precursor of this form from the teleost fish Haplochromis burtoni. This is the second GnRH-encoding gene to be characterized in this species. The newly discovered preprohormone gene differs from tha t previously reported in two ways. First, whereas the original gene pr edicts only a single associated peptide, this one predicts two associa ted peptides, both of which appear to be unique. Second, the gene for [His(5),Trp(7),Tyr(8)]GnRH is expressed in only one cell group in the mesencephalon. In contrast, the previously reported gene is expressed only in the terminal nerve. The striking differences between the prepr ohormone structure and localization suggest that the genes coding for the two known GnRH forms in H. burtoni did not arise from a recent dup lication event. Interestingly, neither of the two genes found to date in this-species is expressed in cells which project from the hypothala mus to the pituitary, suggesting that yet a third gene coding for GnRH may exist.