Simplified models depicting the roles of gonadotropin-release hormone (Gnrh) and the kisspeptins (Kiss) in the control of vertebrate reproduction. (A) In rodent model species, the Gnrh neuronal system is typically viewed as the key integrator of multiple stimulatory and inhibitory inputs that control Gnrh pulsatility, Lh synthesis and the Lh surge in females. Gnrh neurons project to and release the Gnrh peptide into the median eminence (ME). The hypothalamo-hypophysial portal blood transports Gnrh (and other neuropeptides and neurotransmitters) to the anterior pituitary where gonadotrophs are randomly distributed. Specific populations of Kiss-expressing neurons control specific populations of Gnrh neurons. The Kiss-Gnrh pathway is shown as a functional unit framed with a box. In this context, the Kiss and Gnrh systems are in series. Numerous other neuropeptides and neurotransmitters (Nx; for simplicity, depicted as a single input) are important for the control of Gnrh, kisspeptin and, ultimately Lh release and gonadal function. Gonadal steroids such as estradiol-17β (E2) exert both positive and negative feedback at the levels of hypothalamus and pituitary. Elimination of either Gnrh or Kiss blocks reproduction in a mammal. Experimental data have delineated this essentiality of Gnrh and Kiss in the control of Lh release in mammalian species. (B) In teleost fish, the ME has been lost to varying degrees during the course of evolution, and alternatively there is extensive direct innervation of gonadotrophs in the highly regionalized pars distalis of the anterior pituitary. The hypophysiotropic Gnrh neuronal system in teleosts is considered as a key element in the multifactorial direct control of Lh synthesis and release. The role of Kiss is less clear. There is little anatomical evidence supporting the existence of Kiss projections to Gnrh neuronal cell bodies, and Gnrh neurons in teleosts do not express Gpr54. On the other hand, Kiss fibers and Gnrh fibers share a close relationship in the pars distalis. In this context, the Kiss and Gnrh systems (and many others) are in parallel. Gonadal steroids such as E2 exert both positive and negative feedback at the levels of telencephalic preoptic area-hypothalamus and pituitary. Knockout of either Gnrh or Kiss does not block reproduction in a fish. Experimental data have delineated that Gnrh and Kiss are therefore dispensible for reproductive control in zebrafish. Numerous other neurons producing neuropeptides and neurotransmitters (Nx; depicted as multiple inputs. See also Table 1) are important for the control of Gnrh, Kiss and additionally, project to the anterior pituitary for the direct control of Lh and, in turn, gonadal function.