Biology Reference
In-Depth Information
Introduction
A clear understanding of the anatomy of the kisspeptin system is a necessary foundation
for current and future work on the physiology and pathology of kisspeptin. Indeed,
the early recognition of two distinct subpopulations of kisspeptin cell bodies in
rodents was critical to the development of current models for the role of kisspeptin in
mediating the feedback actions of steroids [
1
]. As the physiological functions of kiss-
peptin expand, knowledge of the phenotype, and of the afferent and efferent connec-
tions, of different kisspeptin cell populations becomes even more critical. Thus, the
primary purpose of this chapter is to review our current understanding of this neural
circuitry. The neuroanatomy of this system has been reviewed in the last few years
[
2
-
4
] so this material should be considered an update of these reviews, with an
emphasis on comparative aspects of kisspeptin neuroanatomy in mammals. It is
important to recognize that there is also considerable information on this subject in
nonmammalian species, particularly in fi sh, but this is beyond the scope of our chap-
ter. Interested readers are referred to recent reviews of this topic [
5
,
6
] and Chap.
2
.
This review will focus on distribution of kisspeptin cell bodies, fi bers, and kisspeptin
receptors, with some discussion of the overlap of the latter two. We will also consider
co-localization of neuropeptides, steroid receptors, and other neurotransmitters in differ-
ent kisspeptin subpopulations and evidence on where these subpopulations project.
Finally, we think it is important to consider developmental neuroanatomy and sexual
dimorphism of the kisspeptin system. Although this will be somewhat redundant with
other chapters in this topic, this information is required for a full understanding of the
current neuroanatomical literature on kisspeptin expression in mammals.
Distribution of Kisspeptin and
Kiss1
in the Adult Brain
Since the discovery of its central role in reproduction in 2003, there have been a
number of studies documenting the localization of kisspeptin in the brain using
either immunocytochemistry (ICC) for cell bodies and fi bers or in situ hybridization
(ISH) for cell bodies. The original studies using ICC to identify kisspeptin-positive
cells and fi bers were confounded by cross-reactivity of the antibodies with related
peptide members of the RFamide family [
7
], but more recently, a number of antibod-
ies have been generated which have been shown by the use of careful positive and
negative controls to be specifi c to kisspeptin [
8
-
10
]. Using these specifi c antibodies,
and cDNA and RNA probes against kisspeptin sequences, the distribution of kiss-
peptin cells and fi bers has now been mapped out in a variety of mammalian species.
Not surprisingly, much of this work has been done in mice [
8
,
11
-
17
] and rats [
14
,
18
-
25
], but some data is also available in other rodents (hamster [
26
-
29
] and guinea
pig [
30
]). Ruminants, particularly sheep [
9
,
10
,
31
-
35
] and goats [
36
-
38
], have also
been studied extensively, while there is less information on expression in monkeys
[
39
-
43
] and humans [
41
,
44
] (Tables
3.1
and
3.2
).
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