Metabolic Regulation of Kisspeptin - Kisspeptin Signaling in Reproductive Biology - page 366

Fig. 17.3 Schematic diagram of the potential actions of the pancreas-derived hormone, insulin,
and the gut-born hormone, ghrelin, in the metabolic control of reproduction. While insulin exerts
stimulatory/permissive effects on the reproductive axis, experimental data from different species
supports a predominant inhibitory role of ghrelin the control of puberty and reproduction. Evidence
supporting (or not) the potential link of these hormones with the hypothalamic Kiss1 system is
itemized
function as stimulatory factor for Kiss1 expression, since Kiss1 mRNA levels are
decreased in the hypothalamus of NPY KO mice, whereas NPY enhanced Kiss1
mRNA expression in the hypothalamic cell line, N6 [ 23 ]. Such stimulatory effect is
somewhat counterintuitive, given the proven increase of NPY expression following
conditions of negative energy balance, in which both Kiss1 and the gonadotropic axis
appear to be suppressed, and the documented inhibitory effects of NPY on GnRH
secretion [ 72 ]. Yet, it is also known that at certain physiological and experimental
conditions, NPY may drive a stimulatory signal to the GnRH system [ 73 ]; conditions
where Kiss1 pathways might operate as putative effector. In any event, since leptin
has been shown to suppress the expression of NPY at specifi c neuronal populations
in the ARC [ 74 ], NPY is not likely to operate as a mediator for the stimulatory effects
of leptin on Kiss1 neurons, but rather to act as independent modulator.
In addition, melanocortins, which are anorectic neuropeptide products of
proopio-melanocortin (POMC) neurons in the ARC, have been recently suggested
to stimulate hypothalamic Kiss1 gene expression at the preoptic area in the sheep
[ 75 ]. In contrast, the orexigenic neuropeptide, melanin-concentrating hormone
(MCH), which is prominently expressed in the lateral hypothalamus, suppressed
kisspeptin-induced stimulation of GnRH neurons [ 76 ]. Yet, to our knowledge, the
effects of MCH on Kiss1 expression have not been reported to date. Finally, insulin