Kisspeptin signalling and its roles in humans

Abstract

Kisspeptins are a group of peptide fragments encoded by the KISS1 gene in humans. They bind to kisspeptin receptors with equal efficacy. Kisspeptins and their receptors are expressed by neurons in the arcuate and anteroventral periventricular nuclei of the hypothalamus. Oestrogen mediates negative feedback of gonadotrophin-releasing hormone secretion via the arcuate nucleus. Conversely, it exerts positive feedback via the anteroventral periventricular nucleus. The sexual dimorphism of these nuclei accounts for the differential behaviour of the hypothalamic-pituitary-gonadal axis between genders. Kisspeptins are essential for reproductive function. Puberty is regulated by the maturation of kisspeptin neurons and by interactions between kisspeptins and leptin. Hence, kisspeptins have potential diagnostic and therapeutic applications. Kisspeptin agonists may be used to localise lesions in cases of hypothalamic-pituitary-gonadal axis dysfunction and evaluate the gonadotrophic potential of subfertile individuals. Kisspeptin antagonists may be useful as contraceptives in women, through the prevention of premature luteinisation during in vitro fertilisation, and in the treatment of sex steroid-dependent diseases and metastatic cancers.

Prenatal Exposure of Kisspeptin Antagonist on the GonadotropinReleasing Hormone (GnRH) Expression in Rat Model of Polycystic Ovary Syndrome

“…These animals exhibit elevated LH pulse frequency and irregular reproductive cycles, which may result from a number of mechanisms, including alterations in synaptic input to GnRH neurons, 2004, desensitization of GnRH neurons to steroid feedback, increased amplitude/frequency of GnRH pulses, and increased gonadotropic sensitivity to the GnRH stimulation [20][21][22][23][24]. Kisspeptin, an essential gatekeeper of puberty onset and GnRH secretion, mediates steroid feedback and metabolic cues during different developmental stages throughout the lifespan [9,25]. In addition, kisspeptin is involved in the pathophysiology of the HPG axis; e.g., in PCOS animal models, the hypothalamic expression of kiss 1 and GnRH is abnormal, which might lead to multiple tissue abnormalities, observed in this syndrome [26].…”

Central precocious puberty: From genetics to treatment

“…Based on animal studies, such an approach would render LH concentrations within a physiologic M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 15 rather than a sub-physiologic range which might have advantages in terms of linear growth [64]. To date, no medication that targets the kisspeptin system has been developed that is ready for prime time in the clinical arena.…”

Insights into the putative role of leptin in various traversing stages of women: A narrative review

“…Administration of leptin will increase the kisspeptin expression and stimulate the puberty in the female rat. These animal studies suggest that kisspeptin may stimulate GH from anterior pituitary (Semaan et al, 2013;Tng, 2015).…”