Maternal ghrelin plays an important role in rat fetal development during pregnancy.
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.
Nakahara
Keiko
K
Department of Veterinary Physiology, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2155, Japan.
Nakagawa
Mari
M
Baba
Yukiko
Y
Sato
Miho
M
Toshinai
Koji
K
Date
Yukari
Y
Nakazato
Masamitsu
M
Kojima
Masayasu
M
Miyazato
Mikiya
M
Kaiya
Hiroyuki
H
Hosoda
Hiroshi
H
Kangawa
Kenji
K
Murakami
Noboru
N
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
D054439:Ghrelin; D036361:Peptide Hormones; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D001973:Bromodeoxyuridine; D002118:Calcium; D003345:Corticosterone