THE FROG GONADOTROPIN-RELEASING HORMONE-I (GNRH-I) GENE HAS A MAMMALIAN-LIKE EXPRESSION PATTERN AND CONSERVED DOMAINS IN GNRH-ASSOCIATED PEPTIDE, BUT BRAIN ONSET IS DELAYED UNTIL METAMORPHOSIS

Recent evidence indicates a localized origin in the olfactory placode for the mammalian forebrain neurons that express GnRH. To identify the cellular and molecular signals that induce the GnRH phenotype, we clo ned and characterized a cDNA encoding the GnRH prohormone, the precurs or for both GnRH-I and GnRH-associated peptide in the frog, Xenopus la evis, an embryonic model accessible to experimental manipulation. The 396-base cDNA represented a single mRNA species encoding an 89-amino a cid prepro-GnRH that, unlike a recently cloned fish GnRH gene, was ide ntical to both the mammalian GnRH decapeptide as well as multiple doma ins within GnRH-associated peptide. Serial section in situ hybridizati on histochemistry and immunocytochemistry in adult frog localized a fo rebrain system comprising 250-350 cell bodies whose overall neuroanato my, including fiber projections, was very similar to that described fo r mammals. However, neither Northern nor in situ hybridization detecte d GnRH expression in mid-brain, arguing that another frog gene encodes the midbrain GnRH-II expression pattern described by many others usin g antisera directed against the fish GnRH-I or chicken GnRH-II decapep tides. In contrast to mammals and birds, in which GnRH-expressing cell s migrate into embryonic forebrain, frog GnRH cells were first detecte d after they reached their final position in the preoptic area during the late larval period. Thus, although previous studies proposed a com plex organization for the GnRH system in the frog, our findings show t hat similar to mammals, there is a single gene that can account for th e continuum of GnRH-I cells spanning frog forebrain. However, unlike m ammals, in frogs, for unknown reasons, GnRH-I gene expression is suppr essed until metamorphic climax.