The Role of Kisspeptin in the Control of the Hypothalamic-Pituitary-Gonadal Axis and Reproduction

Abstract

The discovery of kisspeptin as a critical central regulatory factor of GnRH release has given people a novel understanding of the neuroendocrine regulation in human reproduction. Kisspeptin activates the signaling pathway by binding to its receptor kisspeptin receptor (KISS1R) to promote GnRH secretion, thereby regulating the hypothalamic-pituitary-gonadal axis (HPG) axis. Recent studies have shown that kisspeptin neurons located in arcuate nucleus (ARC) co-express neurokinin B (NKB) and dynorphin (Dyn). Such neurons are called KNDy neurons. KNDy neurons participate in the positive and negative feedback of estrogen to GnRH secretion. In addition, kisspeptin is a key factor in the initiation of puberty, and also regulates the processes of female follicle development, oocyte maturation, and ovulation through the HPG axis. In male reproduction, kisspeptin also plays an important role, getting involved in the regulation of Leydig cells, spermatogenesis, sperm functions and reproductive behaviors. Mutations in the KISS1 gene or disorders of the kisspeptin/KISS1R system may lead to clinical symptoms such as idiopathic hypogonadotropic hypogonadism (iHH), central precocious puberty (CPP) and female infertility. Understanding the influence of kisspeptin on the reproductive axis and related mechanisms will help the future application of kisspeptin in disease diagnosis and treatment. In this review, we critically appraise the role of kisspeptin in the HPG axis, including its signaling pathways, negative and positive feedback mechanisms, and its control on female and male reproduction.

Functional evaluation of a novel kisspeptin analogue on the reproduction of female goldfish

“…Expression of the kiss1 and kiss1ra genes has also been reported in brain neurons 41 as well as in organs such as the testes, ovaries, pituitary, and pancreas 42 . Kisspeptin increases the secretion of gonadotropins, but for this purpose, it must first stimulate GnRH-producing neurons in the hypothalamus, which must increase Kiss1 receptors on their cell membrane to be stimulated 43 , 44 . Therefore, the action of kisspeptin requires the expression and presence of kiss1ra in GnRH-producing neurons 41 .…”

Genetic variants of G‐protein coupled receptors associated with pubertal disorders

“…KISS1R is expressed in various brain tissues including the hypothalamus and pituitary. 36 The kisspeptin‐KISS1R system is believed to act directly on GnRH neurons in the preoptic area and infundibular nucleus to produce pulsatile GnRH secretion. 23 , 36 Animal studies confirmed that most GnRH neurons express KISS1R (Figure 1 ).…”

Treatment of congenital hypogonadotropic hypogonadism in male patients

“…GnRH is a peptide consisting of 10 amino acids and is encoded by a gene located on chromosome 8. 7) In the fetus, at 14 weeks of gestation, neurons containing GnRH exist in the hypothalamus, As the hypothalamus-pituitary portal system develops, GnRH in the hypothalamus reaches the gonadotroph in the pituitary gland. At 20 weeks of pregnancy, LH and FSH are secreted by the pituitary gland.…”