Kisspeptin system in female reproduction: A next-generation target in the manipulation of sex hormones.

The discovery of the neuropeptide kisspeptin, originally derived from its antimetastatic property affecting malignant melanoma cells, as well as its role in reproductive function, was a milestone in the field of reproductive biology. Conventionally, the capacity for reproductive activity in mammals involves coordinated communication between the hypothalamus, the anterior pituitary, and the gonads [the hypothalamicepituitaryegonadal (HPG) axis]. This includes hypothalamic neuropeptides [gonadotropin-releasing hormone (GnRH), synthesized in GnRH neurons scattered throughout the preoptic area, as well as the organum vasculosum laminae terminalis, and releasing into the portal circulation in a pulsatile manner], gonadotropins [luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secreted by pituitary gonadotroph cells], and sex steroid hormones (androgen secreted by theca cells, as well as estrogen secreted by granulosa cells and progesterone secreted by luteinizing theca and granulosa cells) secreted by the ovaries. However, there have been significant advances in our understanding of the hierarchical pathways that control GnRH release, where it has been particularly noted that peptides and signaling pathways regulate GnRH neuronal activity. Evidence now indicates that kisspeptins, encoded by the KISS1 gene and secreted by kisspeptin neurons, are critical regulators of sexual differentiation and maturation, as well as normal adult reproduction function in female mammals (menstrual cycles in women and estrous cycles in rodents). Kisspeptin neurons are localized in the arcuate nucleus and the rostral periventricular nucleus of the third ventricle or the preoptic area. The latter releases kisspeptin to gonadotrophs (GnRH neurons) and is mediated by kisspeptin receptors (Kiss1r) that are highly expressed in GnRH neurons and in other areas of the brain, as well as in most endocrine tissues, including the pituitary gland, ovary, and placenta. The study by Luo et al in this issue of the Journal of the Chinese Medical Association entitled, “Expression of kisspeptin/kiss1r system in developing hypothalamus of female rat and the possible effects on reproduction development and maintenance” evaluated correlations between activity and/or expression of the kisspeptin/kiss1r system in the hypothalamus of rats and development of rats from Day 7 of infancy to Day