title: Prokineticins in central and peripheral control of human reproduction.
abstract: Prokineticin 1 (PROK1) and (PROK2), are two closely related proteins that were identified as the mammalian homologs of their two amphibian homologs, mamba intestinal toxin (MIT-1) and Bv8. PROKs activate two G-protein linked receptors (prokineticin receptor 1 and 2, PROKR1 and PROKR2). Both PROK1 and PROK2 have been found to regulate a stunning array of biological functions. In particular, PROKs stimulate gastrointestinal motility, thus accounting for their family name "prokineticins". PROK1 acts as a potent angiogenic mitogen, thus earning its other name, endocrine gland-derived vascular endothelial factor. In contrast, PROK2 signaling pathway has been shown to be a critical regulator of olfactory bulb morphogenesis and sexual maturation. During the last decade, strong evidences established the key roles of prokineticins in the control of human central and peripheral reproductive processes. PROKs act as main regulators of the physiological functions of the ovary, uterus, placenta, and testis, with marked dysfunctions in various pathological conditions such as recurrent pregnancy loss, and preeclampsia. PROKs have also been associated to the tumor development of some of these organs. In the central system, prokineticins control the migration of GnRH neurons, a key process that controls reproductive functions. Importantly, mutations in PROK2 and PROKR2 are associated to the development of Kallmann syndrome, with direct consequences on the reproductive system. This review describes the finely tuned actions of prokineticins in the control of the central and peripheral reproductive processes. Also, it discusses future research directions for the use of these cytokines as diagnostic markers for several reproductive diseases.
authors.forename: Wael
authors.initials: W
authors.lastname: Traboulsi
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouillet
authors.forename: Frederic
authors.initials: F
authors.lastname: Sergent
authors.forename: Houssine
authors.initials: H
authors.lastname: Boufettal
authors.forename: Naima
authors.initials: N
authors.lastname: Samouh
authors.forename: Touria
authors.initials: T
authors.lastname: Aboussaouira
authors.forename: Pascale
authors.initials: P
authors.lastname: Hoffmann
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Feige
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benharouga
authors.forename: Nadia
authors.initials: N
authors.lastname: Alfaidy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005091:Exons; D005260:Female; D005768:Gastrointestinal Hormones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008954:Models, Biological; D009154:Mutation; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012098:Reproduction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C467610:PROK1 protein, human; C423608:PROK2 protein, human; C470837:PROKR1 protein, human; C470838:PROKR2 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived