About this Research Topic
In 1996 a novel cDNA called Kiss1 (KI in reference to the place of discovery-Hershey Pennsylvania, home of the famous Hershey Chocolate Kiss- and SS as suppressor sequence) was identified in non-metastatic melanoma cell lines. Its 54 amino-acid product, Kisspeptin-54 (Kp-54), was originally called metastin for its ability to inhibit cancer metastasis through the activation of a G coupled receptor, previously known as GPR54 and currently renamed kisspeptin receptor (KISS1R).
Kp-54 is the longest cleavage product of the kisspeptin precursor protein, but there are shorter active peptides [i.e. Kp-14, Kp-13 and Kp-10] that have been isolated from the human placenta. All these peptides have the ability to bind KISS1R, share the common amidated C-terminal 10 amino-acids and belong to the family of RF-amide peptides.
Since the distribution of KISS1R in biological tissues, and especially in the brain of mammalian and non-mammalian vertebrates, kisspeptins were thus conceived not only as metastasis suppressors, but as a new family of evolutionarily conserved biological modulators.
In both rodents and humans, genetic ablation or inactivating mutations of the Kiss1/Kiss1R genes cause lack of sexual maturation and hypogonadotropic hypogonadism, with impairment of gametogenesis and altered development of the reproductive organs. Conversely, functionally activating mutations of Kiss1/Kiss1R genes cause precocious puberty.
As a consequence of these findings, most studies have focused on the involvement of kisspeptin activity in the central control of reproduction, through the regulation of hypothalamic Gonadotropin Releasing Hormone (GnRH) neurons which in turn sustain the discharge of gonadotropins and the synthesis of sex steroids. Thus, kisspeptin activity has been extensively characterized in the hypothalamus of mammals revealing three main functions for kisspeptin-releasing neurons: 1) they are the main gatekeeper of the reproductive axis at puberty onset; 2) they switch on/off sex steroid-dependent feedbacks; 3) they are capable of integrating information about the hormonal milieu, environmental factors, stress signals, metabolism and energy balance and conveying this information to GnRH secreting neurons. Consequently, the focus on the central role of the kisspeptins has led to neglecting their possible activities in peripheral tissues. Increasing data reveals that kisspeptins, and KISS1R, have a wider expression and possibly a broader spectrum of action in several peripheral tissues such as the gonads, adipose tissue, and liver with direct consequences on gamete quality and fertility rate, pregnancy, energy homeostasis and body weight control.
All these data clearly encourage us to devote attention to the peripheral activity of kisspeptins since these may represent promising therapeutic approaches for the treatment of cancer and other human diseases, infertility in both sexes and metabolic disorders.
This Research Topic aims at collecting a series of reviews and original research articles to provide a comprehensive picture of the recognized and the emerging knowledge about kisspeptin activity. Such a volume is highly timely, at present missing, and it will be highly attractive to a wide community of researchers in the field and for the community at large.
Keywords: Kisspeptin, HPG axis, puberty onset, metabolism, cancer
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