ABSTRACT
The pairing of the kisspeptins (KP) with the KISS1 (GPR54) receptor has received growing attention since the description of the receptor as a molecular switch for puberty. The role of KP and its receptor, GPR54, in puberty is the most exciting finding made in the field of reproductive biology since the discovery of Gonadotropin Releasing Hormone (GnRH) in 1970s. A significant body of evidence across several species now suggests that KISS1 (GPR54) activation is a critical point in the commencement of puberty, although further investigation is required to characterize the interaction between KP and GnRH cascade. Given such pivotal roles of kisspeptins and GPR54 as gatekeepers of reproductive function, and the proven ability of sex steroids to physiologically regulate this system, it is plausible that environmental compounds with ability to interfere oestrogen and/or androgen signaling (agonists or antagonists) may target the hypothalamic kiss-1/GPR54 system, thereby inducing functional alterations of the hypothalamic-pituitary-gonadal axis. Synthetic agonists targeting KISS1 (GPR54) may represent novel therapeutic agents for the treatment of hypogonadotrophic hypogonadism in some affected individuals. The diverse multifunctional nature of the KP is beginning to unravel. The unexpected role of these peptides in puberty has raised a number of important questions that remain to be answered.
