BACKGROUND: Ghrelin, a peptide hormone produced mainly in the stomach, is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). The existence of placental ghrelin and its receptor has been confirmed in normal pregnancy. However, few reports have so far referred to placental ghrelin and its receptor in intrauterine growth restriction (IUGR). OBJECTIVES: The dynamics of ghrelin production and its receptor expression was investigated to clarify the role of placental ghrelin in an IUGR pregnancy using pregnant Dahl salt-sensitive (Dahl S) rats as a model for IUGR. METHODS: Pregnant Dahl S rats were fed a high-salt diet to develop hypertensive pregnancy with IUGR (IUGR-preg). The levels of ghrelin peptide in the placenta, stomach and plasma of the dams, together with the expression levels of mRNAs for ghrelin and its functional receptor (GHS-R1a) in the placenta, were measured in the IUGR-preg rats at 2 and 3 weeks of gestation, and compared to those in the control pregnant Dahl S rats fed standard chow (Normal-preg). RESULTS: The levels of placental ghrelin peptide at 2 weeks of gestation and placental ghrelin mRNA at each gestational week in IUGR-preg were significantly higher than those in Normal-preg. The level of GHS-R1a mRNA in the placenta of IUGR-preg, which was lower at 2 weeks of gestation in comparison to Normal-preg, significantly increased from 2 to 3 weeks of gestation. No significant difference was observed in the level of ghrelin peptide in the plasma or stomach of the dams between the two groups. CONCLUSION: The profile of placental ghrelin production and the expression of its receptor using Dhal S rats in the IUGR-preg was different from that in the control. The placental ghrelin-ghrelin receptor system thus continues to work until the term of pregnancy in the IUGR-preg in contrast to Normal-preg, which might act as a compensational mechanism for fetal growth.
Fetal Growth Retardation/metabolism , Ghrelin/metabolism , Placenta/metabolism , Receptors, Ghrelin/metabolism , Animals , Disease Models, Animal , Female , Fetal Growth Retardation/chemically induced , Gastric Mucosa/metabolism , Gene Expression Regulation, Developmental/drug effects , Ghrelin/genetics , Hypertension/chemically induced , Hypertension/metabolism , Placenta/drug effects , Pregnancy , RNA, Messenger/metabolism , Rats , Rats, Inbred Dahl , Receptors, Ghrelin/genetics , Sodium Chloride, Dietary/administration & dosage , Stomach/drug effects
