The role of neuropeptides and neurotransmitters on kisspeptin/kiss1r-signaling in female reproduction

Reproductive function is regulated by the hypothalamic-pituitary-gonads (HPG) axis. Hypothalamic neurons synthesizing kisspeptin play a fundamental role in the central regulation of the timing of puberty onset and reproduction in mammals. Kisspeptin is a regulator of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH). In female rodent, the kisspeptin (encoded by kiss1 gene), neurokinin B (Tac3) and dynorphin neurons form the basis for the “KNDy neurons” in the arcuate nucleus and play a fundamental role in the regulation of GnRH/LH release. Furthermore, various factors including neurotransmitters and neuropeptides may cooperate with kisspeptin signaling to modulate GnRH function. Many neuropeptides including proopiomelanocortin, neuropeptide Y, agouti-related protein, and other neuropeptides, as well as neurotransmitters, dopamine, norepinephrine and γ-aminobutyric acid are suggested to control feeding and HPG axis, the underlying mechanisms are not well known. Nonetheless, to date, information about the neurochemical factors of kisspeptin neurons remains incomplete in rodent. This review is intended to provide an overview of KNDy neurons; major neuropeptides and neurotransmitters interfere in kisspeptin signaling to modulate GnRH function for regulation of puberty onset and reproduction, with a focus on the female rodent.