Kisspeptin is an Arg-Phe-NH
2 (RF-amide) peptide encoded by the
KISS1 gene [
10]. The
KISS1 gene was named after Hershey’s chocolate kisses because it was initially isolated from human non-metastatic pigment tumours in Hershey (Pennsylvania, USA), and the “SS” represents “suppressor sequence” [
11]. In humans, the
KISS1 gene is located on chromosome 1q32.11 and encodes a 145-amino acid peptide that is cleaved into four shorter peptides: KP-54, KP-14, KP-13, and KP-10 of 54, 14, 13 and 10 amino acids, respectively. These forms all share a common C-terminal decapeptide (KP-10), which is required for binding with its receptor KISS1R (also known as GPR54) [
12]. In humans, kisspeptin is synthesized in two major sections of the hypothalamus: the arcuate nucleus and the anterior ventral periventricular nucleus [
13]. The binding of kisspeptin to KISS1R activates the phospholipase C pathway in hypothalamic cells, leading to changes in cellular activity [
14]. Current evidence suggests that the kisspeptin signalling pathway is essential for the onset of mammalian puberty. Loss of KISS1R function causes human hypogonadotropic hypogonadism (HH), and one manifestation of HH is the failure to establish puberty due to impaired gonadotropin secretion [
15]. The phenotype of human
KISS1R mutation is mimicked in
Kiss1r knockout mice [
16]. In addition,
Kiss1 knockout rats lack the pulsing and proliferative patterns of gonadotropin and show puberty failure [
17]. Conversely, mutations that cause hyperactive KISS1R in humans lead to central precocious puberty [
18,
19]. These results suggest that kisspeptin plays an integral role in the regulation of pubertal onset. However, emerging evidence indicates the involvement of extra-hypothalamic kisspeptin and the KISS1R system in peripheral reproductive functions.