CHARACTERIZATION OF 2 NEW PREPROGNRH MESSENGER-RNAS IN THE TREE SHREW- FIRST DIRECT EVIDENCE FOR MESENCEPHALIC GNRH GENE-EXPRESSION IN A PLACENTAL MAMMAL

Reproductive maturation and regulation is centrally orchestrated by go nadotropin-releasing hormone (GnRH). GnRH produced in the vertebrate h ypothalamus acts on the pituitary to regulate gonadotropins. In nonpla cental mammalian species, it has recently been shown that a second GnR H gene is expressed in mesencephalic cells. Here, we report the cDNA s equences and expression patterns for two distinct genes encoding the h ypothalamic and mesencephalic GnRH forms in the brain of a placental m ammal, the tree shrew (Tupaia glis belangeri). The novel mammalian GnR H form, designated here as [His(5)Trp(7)Tyr(8)]GnRH (often sailed chic ken GnRH II), is expressed in neurons of the mesencephalon and is the first nonhypothalamic form to be isolated from a mammal. Its peptide s equence is identical to the form previously reported in fish, amphibia ns, reptiles, and birds, revealing that it has remained unchanged for 500 million years. In contrast, the sequences of the hypothalamic GnRH decapeptides vary by as much as 50% across vertebrate species. The re markable sequence conservation of mesencephalic GnRH suggests that it has been highly constrained throughout evolution, perhaps indicating a n important, consented nongonadotropic role. The discovery and localiz ation of two mRNAs encoding distinct GnRH forms in an advanced mammal suggest that other mammals, including primates, may also have a second GnRH gene with expression localized in the midbrain. (C) 1996 Academi c Press, Inc.