Structure, Synthesis, and Phylogeny of Kisspeptin and its Receptor - Kisspeptin Signaling in Reproductive Biology - page 14

To our knowledge, there has been no report on the kisspeptin neuronal systems
of nonmammalian species other than teleosts and placental mammals, and there is a
big gap between these two branches of animals. In fact, during the long history of
vertebrate phylogeny, birds are the only species that have lost both kiss1 and kiss2 ,
suggesting that the kisspeptin system may have increased genetic fi tness in each
species. Thus, the identifi cation of the general functions in vertebrates, including
the regulation on HPG axis, is yet to be concluded.
Steroid Sensitivity of Kisspeptin Neurons
Is Conserved Among Vertebrates
As discussed above, the kisspeptin system has been suggested to play important
roles in the regulation of reproduction in mammals, but not in birds, while it may
also be involved in the regulation of some reproductive functions in teleosts. From
the survey of literature on the functional aspects of kisspeptin in vertebrates, the
apparent conservative nature of the kisspeptin-Gpr54 system undoubtedly suggests
considerable contribution of kisspeptin on “evolutionary fi tness.” Interestingly, the
sex steroid sensitivity of kisspeptin-expressing neurons appears to be well con-
served among teleosts [ 36 - 39 ] and mammals [ 40 - 44 ], suggesting that this sex ste-
roid sensitive nature of kisspeptin neurons was already present before the divergence
of teleosts and tetrapods; the steroid sensitivity is likely to be a general feature of all
the kisspeptin systems throughout vertebrates. As described in the previous section,
in placental mammals, the Kiss1 neurons are strongly suggested to mediate sex
steroid feedback effects; these neurons receive sex steroid signals from the gonads
and directly and/or indirectly modulate the activity of GnRH1 neurons [ 10 - 15 ]. The
mediators of sex steroid feedback, i.e., the neurons that directly receive sex steroids
and control the release of GnRH, have long been searched for, because GnRH neu-
rons themselves lack estrogen receptor alpha (reviewed in ref. [ 45 ]), which is essen-
tial for the sex steroid control of reproduction in mammals [ 46 - 48 ]. Because Kiss1
neurons in mammals express ER alpha, and Kiss1 mRNA expression in many pla-
cental mammalian species is negatively regulated in the arcuate nucleus and posi-
tively regulated in the anteroventral periventricular nucleus (AVPV)/preoptic area
(POA) [ 20 , 40 - 44 , 49 , 50 ], the Kiss1 neurons are the most plausible candidate as the
“missing link” in the steroid feedback mechanism. From several lines of recent
experimental evidence, it is now hypothesized that the arcuate kisspeptin neurons
and the AVPV kisspeptin neurons are involved in negative and positive feedback,
respectively [ 40 , 51 ] (see Chap. 13 ).
In nonmammalian species, the sex steroid sensitivity of kisspeptin neurons has
been demonstrated experimentally only in teleosts, medaka, and goldfi sh [ 36 , 39 ].
In medaka, among several populations of kiss1 and kiss2 neurons in the brain, only
the kiss1 neurons in a hypothalamic nucleus, nucleus ventralis tuberis (NVT), show
sex steroid sensitivity; NVT kiss1 expression is positively regulated by gonadal
steroids, probably directly via sex steroid hormone receptors [ 36 , 39 ]. On the other