[6] Kisspeptin-GPR54 signaling has an important role in initiating secretion of gonadotropin-releasing hormone (GnRH) at puberty, the extent of which is an area of ongoing research.

Kisspeptin was found to play a role in hypogonadotropic hypogonadism in 2003, which was supported by several independent lab groups.

[11] Several other phenotypes related to this mutation included a smaller sex steroid and gonadotropin concentration in the circulating blood and even sterility.

[13] Kisspeptin is most notably expressed in the hypothalamus, but is also found in other areas of the brain including the hippocampal dentate gyrus.

[14] The neuropeptide kisspeptin plays an important role in reproduction, but also stimulates aldosterone secretion from the adrenal cortex.

The exact nature of the expression of kisspeptins in human adrenal glands unfortunately has not been fully clarified yet and remains a large topic of research among many scientists.

[17] Different types made up of 14 and 13 amino acids have been isolated and they each share a common C-terminal sequence.

Among these conserved amino acids are arginine and phenylalanine residues, which are paired in this family of peptides.

When the adenosine is absent, a downstream stop codon is used, and the encoded protein extends for an additional seven amino acid residues.

Each of these fragments has a similar conserved region at the C-terminal sequence consisting of ten amino acids.

The sequence on the carboxy terminal side of the conserved region is a well-known site for cleavage in neuropeptides.

[11] It is composed of 398 amino acids that form seven transmembrane domains, like most G-protein coupled receptors.

Variation appears in the around the amino and C-terminal domains, which accounts for the different types of Kisspeptin receptors seen in various species.

Evidence for this involves the persistence of a neural response to kisspeptin levels even in the presence of TTX, a neurotoxin that blocks nerve signals.

The onset of puberty is marked by an increase in gonadotropin secretion, which leads to sexual maturity and the ability to reproduce.

[17] Several studies have confirmed that addition of kisspeptin to biological systems including rat, mouse, and sheep are able to bring about the release of LH and FSH.

In rat hypothalamus, it was found that over three-fourths of GnRH neurons coexpress the receptor for kisspeptin, GPR54, in their RNA.

This suggests that there is greater expression of KISS1 and potentially even GPR54 at the onset of puberty leading to an increase in kisspeptin/GPR54 signaling that results in the activation of the gonadotropin pathway.

[16] Kisspeptin-54 has undergone early clinical trials as a potential medication for the treatment of low libido, with a single intravenous infusion of kisspeptin-54 being well tolerated and showing some evidence for efficacy in both men and women diagnosed with hypoactive sexual desire disorder.

[21][22] Kisspeptin and its receptor was found in various sites in the kidney, including in the collecting duct, vascular smooth muscle, and in the renal tubule cells.

[23] Much of the impact on the kidney deals with the increased production of aldosterone in the adrenals glands stimulated by kisspeptin.

[24] Aldosterone that comes from the neighboring adrenal glands causes reabsorption of filtrate in order to retain water, leading to an increased blood pressure.

However, for kisspeptin to be involved in the regulation of GnRH release, it must also be sensitive to circulating sex steroid levels, as it is established that steroids produced by the gonads exert regulatory effects on FSH and LH levels through GnRH mediation.