title: Maternal ghrelin plays an important role in rat fetal development during pregnancy.
abstract: Ghrelin, an acylated peptide serving as an endogenous ligand for GH secretagogue receptor (GHS-R), was originally isolated from rat and human stomach. In this study, we report the critical role of maternal ghrelin in fetal development. High levels of ghrelin receptor (GHS-R) mRNA were detected in various peripheral fetal tissues beginning at embryonic d 14 and lasting until birth. Fetal GHS-R expression was also confirmed in fetal tissues by immunohistochemistry. Autoradiography revealed that both des-acyl ghrelin and acyl ghrelin bind to fetal tissues. Chronic treatment of mothers with ghrelin resulted in a significant increase in birth weight in comparison to newborns from saline-treated mothers. Even when maternal food intake after ghrelin treatment was restricted through paired feeding, significant stimulation of fetal development still occurred. Conversely, active immunization of mothers against ghrelin decreased fetal body weight during pregnancy. A single ghrelin injection into the mother increased circulating ghrelin levels in the fetus within 5 min of injection, suggesting that maternal ghrelin transits easily to the fetal circulation. High levels of des-acyl ghrelin were detected in fetal blood and amniotic fluid. Both acylated and des-acyl ghrelin increased [3H]thymidine and 5-bromo-2'-deoxyuridine incorporation of cultured fetal skin cells in a dose-dependent manner, and calcium-imaging analysis revealed that acyl and des-acyl ghrelin increased the Ca2+ influx in discrete cultured fetal skin cells, respectively. These results indicate that maternal ghrelin regulates fetal development during the late stages of pregnancy.
authors.affiliation: Department of Veterinary Physiology, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2155, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakahara
authors.forename: Mari
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Baba
authors.forename: Miho
authors.initials: M
authors.lastname: Sato
authors.forename: Koji
authors.initials: K
authors.lastname: Toshinai
authors.forename: Yukari
authors.initials: Y
authors.lastname: Date
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
authors.forename: Masayasu
authors.initials: M
authors.lastname: Kojima
authors.forename: Mikiya
authors.initials: M
authors.lastname: Miyazato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kaiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoda
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Noboru
authors.initials: N
authors.lastname: Murakami
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism; D047108:Embryonic Development; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018507:Gene Expression Regulation, Developmental; D054439:Ghrelin; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D036361:Peptide Hormones / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D011270:Pregnancy, Animal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D054439:Ghrelin; D036361:Peptide Hormones; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D001973:Bromodeoxyuridine; D002118:Calcium; D003345:Corticosterone