Description

Kisspeptin is a peptide product of the KiSS-1 gene and mediates its action via the G-protein coupled receptor, GPR54. Both KiSS-1 mRNA and GPR54 receptors are highly expressed in a number of tissues including the hypothalamus and placenta.

It is now known that kisspeptin plays a central role in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis. Indeed, loss of function mutations of the GPR54 receptors result in hypogonadotropic hypogonadism.

Several studies have identified kisspeptin as a potent stimulator of LH and FSH release in animals and humans. LH release is a 100 times more sensitive to stimulation by kisspeptin than FSH. Further, kisspeptin is thought to play a role in the pre-ovulatory LH surge and is considered to be an important trigger for the biochemical changes associated with the onset of puberty.

There is KiSS-1 expression in both the arcuate (ARC) and anteroventeral para ventricular (AVPV) nuclei of the hypothalamus. Expression in the ARC is enhanced in post-gonadectomy and this enhancement is suppressed by exogenous sex steroids. The opposite effect occurs in the AVPV. This suggests that kisspeptin is sensitive to circulating steroid levels, and is important in the feedback mechanisms of the HPG axis.
In conclusion, kisspeptin is a central regulator of the HPG axis. Human studies have shown that exogenous kisspeptin is a potent stimulator of LH and has a good safety profile. It may therefore be possible to use kisspeptin as a novel therapeutic modulator of the HPG axis.