The role of prokineticins in the pathogenesis of hypogonadotropic hypogonadism

Neuroendocrinology. 2010;91(4):283-90. doi: 10.1159/000308880. Epub 2010 May 21.


The prokineticin system comprises two multifunctional secreted proteins, prokineticin-1 (PROK1) and prokineticin-2 (PROK2), and their cognate G protein-coupled receptors. The prokineticins were originally identified as endogenous regulators of gastrointestinal motility. Currently, these bioactive peptides are involved in a wide spectrum of biological functions, including angiogenesis, neurogenesis, circadian rhythms, nociception, hematopoiesis and immune response. Mice homozygous for null mutations in Prokr2 or Prok2 recapitulate the human phenotype of Kallmann syndrome, exhibiting severe atrophy of the reproductive system and hypoplastic olfactory bulbs. Indeed, the evidence from several naturally inactivating mutations in the PROK2 and PROKR2 genes in patients with Kallmann syndrome and normosmic hypogonadotropic hypogonadism also indicate the essential role of PROK2 in olfactory bulb morphogenesis and GnRH secretion in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Female
  • Gastrointestinal Hormones / genetics*
  • Gastrointestinal Hormones / metabolism
  • Humans
  • Hypogonadism / genetics*
  • Hypogonadism / metabolism
  • Male
  • Mice
  • Mutation
  • Neuropeptides / genetics*
  • Neuropeptides / metabolism
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Peptide / genetics*
  • Receptors, Peptide / metabolism
  • Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / genetics*
  • Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / metabolism


  • Gastrointestinal Hormones
  • Neuropeptides
  • PROK2 protein, human
  • PROKR1 protein, human
  • PROKR2 protein, human
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide
  • Vascular Endothelial Growth Factor, Endocrine-Gland-Derived