Kisspeptin is a 54-amino acid peptide which is encoded by the KiSS-1 gene and activates the G protein-coupled
receptor GPR54. Evidence suggests that this system is a key regulator of mammalian and human reproduction. Animal
studies have shown that GPR54-deficient mice have abnormal sexual development. Central and peripheral administration
of kisspeptin stimulates the hypothalamic-pituitary-gonadal (HPG) axis whilst pre-administration of a gonadotrophin releasing
hormone (GnRH) antagonist abolishes this effect.
In humans, inactivating GPR54 mutations cause normosmic hypogonadotrophic hypogonadism whilst activation of
GPR54 signalling is associated with premature puberty. In healthy human volunteers, the acute intravenous administration
of kisspeptin potently increases plasma luteinising hormone (LH) levels and significantly increases plasma follicle stimulating
hormone (FSH) and testosterone without side effects in both males and in females particularly in the preovulatatory
phase of the menstrual cycle. In infertility due to hypothalamic amenorrhoea acute administration of kisspeptin
results in stimulation of reproductive hormones.
The kisspeptin/GPR54 system therefore appears to play an important role in the regulation of reproduction in humans.
Hence kisspeptin has potential as a novel tool for the manipulation of the HPG axis and treatment of infertility in humans.
This review discusses the evidence highlighting kisspeptin’s key role in human reproduction.
Keywords: Kisspeptin, reproduction, infertility, LH, FSH, testosterone, GnRH, menstrual, puberty, Hypothalamo-pituitary-gonadal
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