Gastrointestinal hormones (anorexigenic peptide YY and orexigenic ghrelin) influence neural tube development.
Gastrointestinal (GI) hormones play an important role in GI secretion, motility, and eating behaviors. It was recently suggested that GI hormones may have a trophic role in GI tract. Here we demonstrate that two principal GI hormones, anorexigenic peptide YY (PYY) and orexigenic ghrelin, affect neural tube development. Chronic administration into the pregnant mice or transgenic overexpression of PYY led to a neural tube defect (NTD) in the embryos that was blocked by ghrelin. PYY Y1 receptor antagonist prevented the occurrence of NTD induced not only by PYY but also by vitamin A, a well-known teratogen in humans and animals. Y1 receptor deficiency also engendered NTDs, indicating the need to maintain normal Y1 receptor signaling. The present study is the first linking GI hormones to the leading cause of infant mortality and provides a novel insight for neurogenesis in which materno-fetal communication through GI hormones appears to be important.
Yuzuriha
Hideki
H
Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Inui
Akio
A
Asakawa
Akihiro
A
Ueno
Naohiko
N
Kasuga
Masato
M
Meguid
Michael M
MM
Miyazaki
Jun-ichi
J
Ninomiya
Maiko
M
Herzog
Herbert
H
Fujimiya
Mineko
M
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000627:therapeutic use; D001921:Brain / Q000002:abnormalities / Q000196:embryology; D001923:Brain Chemistry; D003510:Cyclohexanes / Q000627:therapeutic use; D004435:Eating / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D005804:Genes, Lethal; D005813:Genes, Synthetic; D054439:Ghrelin; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009436:Neural Tube Defects / Q000139:chemically induced* / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D009478:Neuropeptide Y / Q000494:pharmacology; D010191:Pancreatic Polypeptide / Q000633:toxicity; D010446:Peptide Fragments / Q000494:pharmacology; D036361:Peptide Hormones / Q000097:blood / Q000502:physiology* / Q000627:therapeutic use; D019894:Peptide YY / Q000097:blood / Q000235:genetics / Q000502:physiology / Q000633:toxicity*; D011247:Pregnancy; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects; D013723:Teratogens / Q000633:toxicity; D014801:Vitamin A / Q000633:toxicity; D014966:Xanthenes / Q000627:therapeutic use
D003510:Cyclohexanes; D054439:Ghrelin; C410588:L 152804; D009478:Neuropeptide Y; D010446:Peptide Fragments; D036361:Peptide Hormones; D017476:Receptors, Neuropeptide Y; D011993:Recombinant Fusion Proteins; D013723:Teratogens; D014966:Xanthenes; C062924:neuropeptide Y (13-36); C097212:neuropeptide Y-Y1 receptor; D019894:Peptide YY; D014801:Vitamin A; D010191:Pancreatic Polypeptide; D005492:Folic Acid; D001120:Arginine; C117416:BIBO 3304; C514549:peptide YY (1-36)