Contraplacental Hypogastrinemic Effect of Gastrin Infusion in Sheep

Abstract

SummaryInfusion of gastrin, G-171, at 0.4 pg/min into either the maternal or fetal venous circulation of six late gestation sheep was associated with increases in serum gastrin concentration in the infused circulation and reciprocal decreases in the serum gastrin concentration in the other circulation (contraplacental) that perfused the placenta. Pentagastrin infusion at 0.4 pg/min was associated with an increase in C-terminal specific gastrin immunoreactivity in both the infused and the contraplacental circulations. These observations suggest that biologically active fragments of gastrin, but not the intact molecule, may cross the ovine placenta. An alternative explanation for our results is that gastrin infusion into either the maternal or fetal circulation which perfuses the placenta may result in the release of an inhibitor (i.e., somatostatin) into the other circulation. Of broad importance, these observations indicate that although intact polypeptide hormones may not traverse the placenta, their concentrations in maternal and fetal sera may not be as independent as previously believed. Serum gastrin half-life values in late gestation sheep fetuses, lambs, and ewes were determined to be 13.7 +: 1.9, 16.7 f 2.6, and 15.2 2 2.8 min, respectively. These similar values indicate that the relatively high serum gastrin concentrations observed in near-term sheep fetuses are not the result of prolonged half-life in the fetus.Gastrin promotes growth of the gastrointestinal tract after birth (1 1, 15). Its role in the development of the fetal gastrointestinal tract, however, has not been clearly defined, nor has the regulation of fetal circulating gastrin concentration been elucidated. Gastrin appears in fetal gastrointestinal tissues and serum late in gestation, and its concentration in the serum increases rapidly, so that at birth there is hypergastrinemia relative to adults in several species (2, 4, 8, 12, 14, 17, 18, 2 1, 22, 26). In sheep, for example, fetal serum gastrin is first detected at about 117 d gestation. It increases linearly thereafter, surpassing the mean maternal serum gastrin concentration (20.0 f 1.5 fmol/ml) after 124 d gestation ( 14). By the end of gestation at 145-147 d, fetal serum gastrin concentration is approximately 3 times the maternal concentration. The lack of correlation between maternal and fetal serum concentrations of gastrin, the absence of an umbilical venoarterial concentration difference, and the demonstration of gastrin present in gastrointestinal tissue concomitant with its appearance in serum in the fetus support the hypothesis that circulating gastrin in the fetus arises from fetal tissues rather than by transplacental passage. Furthermore, as a general observation in most species, polypeptide hormones do not traverse the placenta.On the other hand, there is some evidence that maternal events influence fetal gastrin physiology. Infusion of gastrin into pregnant dogs I wk before term significantly stimulates fetal gastric secretion (5), an observation that suggests the trans...

Evidence for a Role of Volatile Amines in the Development of Neonatal Hypergastrinemia

“…directly related to gastric achloryhdria (4,5,13,14), reduced metabolic clearance of gastrin (11,12), or placental transport of maternal gastrin (12,(19)(20)(21). Other possible explanations, that have not been adequately tested, relate to an extragastric source of gastrin (i.e., duodenal or pancreatic; 22,23), inability of the immature G cell of the neonate to adequately store the hormone, or the presence of luminal or systemic stimulants of gastrin release during the early neonatal period to place the G cell in a hypersecretory state (24).…”