Meeting Abstract

S6-1.6  Saturday, Jan. 5  NOVEL ASPECTS OF THE GONADOTROPIN-RELEASING HORMONE AXIS IN THREE MODEL CHORDATES. TELLO, J.S.**; ADAMS, B.A.; WU, S; SHERWOOD, N.M.; Univ. of Victoria, British Columbia jtello@uvic.ca

In humans, the neurohormone gonadotropin-releasing hormone (GnRH) facilitates reproductive cycling beginning at puberty. GnRH is produced in the hypothalamus and when released, binds to its cognate receptor, GnRHR, present on cells in the anterior pituitary. Activation of GnRHR stimulates the release of gonadotropins leading to gametogenesis and steriodogenesis in the gonads. Humans possess an additional form of GnRH (GnRH2) with no clear function. We used a comparative approach to uncover novel GnRH functions early in the chordate lineage that may be masked in the more complex mammalian system. We characterized the GnRH axis in three model organisms positioned throughout chordate evolution. We found six novel GnRH peptides encoded on two genes in the tunicate, a basal chordate without either a pituitary or the suite of enzymes required to synthesize sex steroids. We further characterized their GnRH receptor complement and found three functional receptors which utilize the cAMP intracellular signaling cascade. More recently, we identified three GnRHRs in the amphioxus genome, another non-vertebrate chordate species. Our initial studies show that both human forms of GnRH stimulate intracellular accumulation of inositol phosphates in amphioxus GnRHR-expressing COS cells, indicating a conserved structure-function relationship over the last 500 million years of evolution. In our last model, the vertebrate zebrafish, we cloned and characterized four functional GnRHRs, each having unique potencies with two endogenous forms of GnRH. The unique expression patterns of multiple receptors and discrete potencies of GnRH ligands in these model organisms suggest a higher level of complexity of the GnRH network outside the classical hypothalamic-pituitary-gonadal axis.