Structure, Synthesis, and Phylogeny of Kisspeptin and its Receptor - Kisspeptin Signaling in Reproductive Biology - page 16

compensated functionally by the closely related Kiss1 gene (for detailed discussion,
see ref. [ 38 ]). From the arguments about the sex steroid sensitivity of kisspeptin neu-
rons thus far, it is suggested that this property of kisspeptin neurons is one of the most
general and important properties among the vertebrate kisspeptin systems; it may
have been already acquired before the divergence of teleosts and tetrapods.
Axonal Projections of the Kisspeptin Neurons
and the Distribution of Kisspeptin Receptors
Projections of Kiss1 Neurons in Mammals
In mammalian species, several studies have analyzed anatomical relationships
between the Kiss1 neurons and the other components in the HPG axis, most impor-
tantly, the GnRH1 neurons. Recently, Clarkson et al. detailed the projections of Kiss1
neurons in the mouse brain [ 53 ]. It was shown that Kiss1-immunoreactive (ir) fi bers
were abundant in the ventral aspect of the lateral septum and the hypothalamus, run-
ning in periventricular and ventral retrochiasmatic pathways, except for the suprachi-
asmatic and ventromedial nuclei. Moreover, Kiss1-ir fi bers were observed in the
internal zone of the median eminence, but not in its external layer where GnRH and
other hypophysiotropic hormone-containing axons are proposed to terminate. In addi-
tion, a small number of kisspeptin fi bers were also observed outside the hypothala-
mus, in the bed nucleus of the stria terminalis, subfornical organ, medial amygdala,
paraventricular thalamus, periaqueductal grey and locus coeruleus. These fi ndings are
consistent with a study in the rat brain using different antiserum, although there were
some discrepancies in the distribution outside the hypothalamus [ 54 ]. In mammalian
species, heavy projections to some hypothalamic and preoptic nuclei now seem to be
the general consensus on the distribution of Kiss1 neurons. Moreover, Kiss1 fi bers
have been shown to project to the median eminence, and make close contacts with
GnRH1 fi bers in mammals [ 55 - 57 ]. Because GnRH1 neurons express gpr54 in mam-
mals, Kiss1 neurons are hypothesized to stimulate GnRH release from GnRH axons
at the nerve terminals in or near the median eminence.
Projections of Kiss1/Kiss2 Neurons in Teleosts
There are a limited number of neuroanatomical studies detailing the axonal projec-
tions of Kiss1 and Kiss2 neurons and the distribution of Gpr54 in nonmammalian
species, and most of the studies have been carried out in teleosts. As described
below, the projections of Kiss1 and Kiss2 neurons in nonmammalian species are
complicated; the steroid sensitive Kiss1 neurons in medaka project to POA, but only
Kiss2 neurons project to POA in zebrafi sh. On the other hand, the distribution of
receptor subtypes show rather consistent results in most teleost studies so far;