Kisspeptin is a brain peptide that tells the reproductive hormone system when to release GnRH, which then triggers the release of sex hormones. It works through two brain areas: one that creates the regular pulses of GnRH and another that creates the big surge needed for ovulation. In mammals, it’s crucial for starting puberty, keeping fertility, and may affect reproductive aging, so scientists think it could become a drug target for fertility problems.

The discovery of Kisspeptin (Kiss) has opened a new direction in research on neuroendocrine control of reproduction in vertebrates. Belonging to the RF amide family of peptides, Kiss and its cognate receptor Gpr54 (Kissr) have a long and complex evolutionary history. Multiple forms of Kiss and Kissr are identified in non-mammalian vertebrates, with the exception of birds, and monotreme mammals. However, only a single form of the ligand (KISS1/Kiss1) and receptor (KISS1R/Kiss1r) is retained in higher mammals. Kiss1 is distributed in the hypothalamus-pituitary-gonadal (HPG) axis and its primary function is to stimulate gonadotropin-releasing hormone (GnRH) secretion. Kiss1 neurons are distributed in the rostral periventricular area of the third ventricle (RP3V) and arcuate/infundibular nucleus (ARN/IFN). The ARN/IFN is considered the GnRH pulse generator controlled by steroid negative feedback, and the RP3V neurons is concerned with GnRH surge induced by steroid positive feedback in females. The Kiss1-Kiss1r signaling is important in all aspects of reproduction: puberty onset, maintenance of adult gonadal functions and reproductive aging, and hence assumes therapeutic potentials in the treatment of reproductive dysfunctions and induction of artificial reproduction. This chapter reviews involvement of Kiss1 in the control of the HPG axis functions in female mammals.