Circulating levels of ghrelin in human fetuses

Objective: Ghrelin is a GH secretagog isolated recently from rat stomach and involved in the stimulation of food intake and adiposity in rodents and humans. Moreover, subsequent studies showed that ghrelin is expressed in rat and human placenta, suggesting a possible influence of the peptide on fetal growth. The aim of this study was to evaluate circulating levels of ghrelin in appropriate for gestational age (AGA) or intrauterine growth-restricted (IUGR) fetuses. Subjects and methods: Ghrelin levels between 20 and 39 weeks of gestation were measured in 16 AGA and nine IUGR fetuses in whom blood was collected by cordocentesis performed for prenatal diagnosis of different diseases or during elective cesarean section. In most samples, GH, cortisol and leptin levels were also evaluated. Results are expressed as means +/- S.D. Differences were tested using the Student's t-test with Welch correction. P < 0.05 was considered significant. Results: All fetuses showed levels of ghrelin in the umbilical venous blood (100 +/- 9 9 pmol/l) that did not correlate with the gestational age or the maternal ghrelin levels. No difference was found between umbilical venous and arterial concentrations, suggesting that fetal tissues are a source of ghrelin. Ghrelin levels in IUGR fetuses were significantly higher than those found in AGA fetuses (176 +/- 125 vs 58 +/- 44 pmol/l; P < 0.005). Moreover, in samples obtained at birth, ghrelin concentrations correlated negatively with birth weight (P < 0.05). In IUGR fetuses, GH and cortisol concentrations were higher and leptin levels lower than in AGA fetuses, although no significant correlation between these parameters and ghrelin levels was found. Conclusion: The presence of ghrelin in the fetal circulation as well as its increase in IUGR fetuses suggest a role of this peptide during intrauterine development.