Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord.
Expressions of the growth hormone secretagogue receptor (GHS-R) mRNA and its protein were confirmed in rat fetal spinal cord tissues by RT-PCR and immunohistochemistry. In vitro, over 3 nM ghrelin and des-acyl ghrelin induced significant proliferation of primary cultured cells from the fetal spinal cord. The proliferating cells were then double-stained using antibodies against the neuronal precursor marker, nestin, and the cell proliferation marker, 5-bromo-2'-deoxyuridine (BrdU), and the nestin-positive cells were also found to be co-stained with antibody against GHS-R. Furthermore, binding studies using [125I]des-acyl ghrelin indicated the presence of a specific binding site for des-acyl ghrelin, and confirmed that the binding was displaced with unlabeled des-acyl ghrelin or ghrelin. These results indicate that ghrelin and des-acyl ghrelin induce proliferation of neuronal precursor cells that is both dependent and independent of GHS-R, suggesting that both ghrelin and des-acyl ghrelin are involved in neurogenesis of the fetal spinal cord.
Sato
Miho
M
Department of Veterinary Physiology, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2155, Japan.
Nakahara
Keiko
K
Goto
Shintaro
S
Kaiya
Hiroyuki
H
Miyazato
Mikiya
M
Date
Yukari
Y
Nakazato
Masamitsu
M
Kangawa
Kenji
K
Murakami
Noboru
N
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D054439:Ghrelin; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D036361:Peptide Hormones / Q000008:administration & dosage*; D051381:Rats; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*
D054439:Ghrelin; D036361:Peptide Hormones; C422650:ghrelin, des-n-octanoyl