3 GONADOTROPIN-RELEASING-HORMONE GENES IN ONE ORGANISM SUGGEST NOVEL ROLES FOR AN ANCIENT PEPTIDE

Gonadotropin-releasing hormone (GnRH) is known and named for its essen tial role in vertebrate reproduction, Release of this decapeptide from neurons in the hypothalamus controls pituitary gonadotropin levels wh ich, in turn, regulate gonadal state, The importance of GnRH is unders cored by its widespread expression and conservation across vertebrate taxa: five amino acids are invariant in all nine known forms, whereas two others show only conservative changes, In most eutherian mammals, only one form, expressed in the hypothalamus, is thought to exist, alt hough in a recent report, antibody staining in developing primates sug gests an additional form, In contrast, multiple GnRH forms and express ion loci have been reported in many nonmammalian vertebrates, However, evidence based on immunological discrimination does not always agree with analysis of gene expression, since GnRH forms encoded by differen t genes may not be reliably distinguished by antibodies, Here we repor t the expression of three distinct GnRH genes in a teleost fish brain, including the sequence encoding a novel GnRH preprohormone. Using in situ hybridization, we show that this form is found only in neurons th at project to the pituitary and exhibit changes in soma size depending on social and reproductive state, The other two GnRH genes are expres sed in other, distinct cell populations. All three genes share the mot if of encoding a polypeptide consisting of GnRH and a GnRH-associated peptide, Whereas the GnRH moiety is highly conserved, the GnRH-associa ted peptides are not, reflecting differential selective pressure on di fferent parts of the gene, GnRH forms expressed in nonhypothalamic reg ions may serve to coordinate reproductive activities of the animal.