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Fig. 17.2
Schematic diagram of the potential actions of leptin in the metabolic gating of puberty
and reproduction, and its potential link with the hypothalamic
Kiss1
system. Evidences for a regu-
latory role of energy balance and leptin on hypothalamic
Kiss1
/kisspeptin expression are summa-
rized in
blue
. Recent data suggesting indirect effects of leptin on
Kiss1
neurons, and
Kiss1
-independent pathways for leptin effects on the reproductive axis, are highlighted in
red
several metabolic studies), but not insulin, to male rats with uncontrolled diabetes,
caused by administration of streptozotocin, has been shown to normalize hypotha-
lamic
Kiss1
gene expression in this model of profound metabolic distress, which is
characterized, among other alterations, by a state of hypogonadotropic hypogonad-
ism, linked to marked hypoleptinemia and hypoinsulinemia [
24
]. Key reproductive
parameters, including LH and testosterone secretion, were ameliorated in diabetic
male rats by central leptin treatment [
24
]. In good agreement with those observa-
tions, leptin was able to increase
Kiss1
gene expression in the murine hypothalamic
cell line, N6 [
23
], as well as in primary cultures of human fetal GnRH-secreting
neuroblasts [
47
]. In the same vein, leptin has been recently reported to induce the
depolarization of
Kiss1
neurons at the ARC via activation of TRPC channels in the
guinea pig [
48
]; a species where ARC
Kiss1
neurons seem to express functional
leptin receptors [
48
]. Additionally, studies in the sheep have documented the
expression of the leptin receptor gene in both ARC and POA
Kiss1
neurons, and
leptin has been shown to increase
Kiss1
mRNA expression in those hypothalamic
nuclei [
30
]. As a whole, these fi ndings support the existence of a leptin-kisspeptin-
GnRH pathway, whereby leptin actions could be signaled onto GnRH neurons via
modulation of kisspeptin afferents, thereby allowing proper maturation and function
of the HPG axis in conditions of energy/leptin abundance.
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