Review of human genetic and clinical studies directly relevant to GnRH signalling

J Neuroendocrinol. 2022 May;34(5):e13080. doi: 10.1111/jne.13080. Epub 2021 Dec 31.

Abstract

GnRH is the pivotal hormone in controlling the hypothalamic-pituitary gonadal (HPG) axis in humans and other mammalian species. GnRH function is influenced by a multitude of known and still unknown environmental and genetic factors. Molecular genetic studies on human families with hypogonadotropic hypogonadism over the past two decades have been instrumental in delineating the kisspeptin and neurokinin B signalling, which integrally modulates GnRH release from the hypothalamus. The identification of kisspeptin and neurokinin B ligand-receptor gene pair mutations in patients with absent puberty have paved the way to a greater understanding of the central regulation of the HPG cascade. In this article, we aim to review the literature on the genetic and clinical aspects of GnRH and its receptor, as well as the two ligand-receptor sets directly pertinent to the function of GnRH hormone signalling, kisspeptin/ kisspeptin receptor and NKB/NK3R.

Keywords: GnRH; hypogonadotropic hypogonadism; kisspeptin; neurokinins; puberty.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Gonadotropin-Releasing Hormone / genetics
  • Human Genetics
  • Humans
  • Kisspeptins* / genetics
  • Ligands
  • Mammals
  • Neurokinin B* / genetics

Substances

  • Kisspeptins
  • Ligands
  • Gonadotropin-Releasing Hormone
  • Neurokinin B