KissWiki Miscellaneous Kisspeptin and gpr-54 are also found in non-reproductive tissues
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The kisspeptin/gpr-54 system has also been shown to have effects in other regions of the brain and periphery not connected with reproduction. In the brain, KiSS-1 and gpr-54 mRNA is located in the hippocampal denate gyrus, where kisspeptin-10 can upregulate the excitory post-synaptic current (EPSC) of the denate granule cells by increasing the amplitude but not frequency of the current.
This increase in synaptic transmission is via a MAPK pathway, which may be regulated via camodulin-dependant kinase (CaMK) and tyrosine kinases mechanisms (Arai et al., 2005). KiSS-1 is up regulated in kainite induced seizures in the hippocampus of rats via an α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) dependant mechanism. Kisspeptin can also increase BDNF levels in the hippocampus, a factor that is critical for hippocampus function and correlates with the severity of seizures in this region (Arai and Orwig, 2008).
In the peripheral systems, kisspeptin has a role as a vasoconstrictor in aortic smooth muscle, where KiSS-1 and gpr-54 mRNA has been localised to the vascular endothelial cells and atherosclerotic plaques of the coronary artery. However, further work is need to discover the relevance of this vasoconstriction and if this system is active in vivo (Mead et al., 2006). In the adrenal gland, gpr-54 mRNA has been localised to the neocortex of human adrenals, with a 50% increase in foetal compared to adult adrenal glands. In this gland, kisspeptin-54 can stimulate secretion of aldosterone into the kidney to regulate fluid levels and blood pressure (Nakamura et al., 2007). In the pancreas, KiSS-1 and gpr-54 mRNA has been found in human and mouse islet cells of the endocrine pancreas, where kisspeptin can stimulate release of glucose-induced insulin, when in a high glucose environment (20mmol/l) in humans and rats. This increase in insulin acts via receptors in the periphery as iv but not icv injection stimulates this increase and this has again been shown to be via ERK1/2 pathway (Bowe et al., 2009; Hauge-Evans et al., 2006). This shows that kisspeptin regulates a wide range of effects in the body; however, reproduction appears to be the most important site of action.
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