In ambulant nursing home and hostel residents, residents who fall have lower serum 25-hydroxyvitamin D and higher serum parathyroid hormone levels than other residents. The association between falling and serum PTH persists after adjustment for other variables.
Heavier weight is associated with both the prevalence and severity of secondary hyperparathyroidism and consistent with animal models of secondary hyperparathyroidism, phosphate may relate to serum PTH independently of 1,25-(OH)2D or calcium.
In the sheep fetus, plasma levels of gastrin are raised above adult levels from 2 weeks before birth. This observation initiated the present study on the maternal and fetal secretion rate, metabolism and placental transfer of gastrin. The experiments were performed on conscious pregnant ewes with chronically cannulated fetuses and on newborn lambs. Metabolic clearance rate (MCR), production rate (PR) and placental transfer of gastrin were measured by alternate steady-state infusion of gastrin into the mother and fetus. Plasma levels of gastrin were measured by radioimmunoassay. Metabolic clearance rate was similar in the pregnant and non-pregnant ewe (8.4 +/- 1.1 (S.E.M.) and 9.0 +/- 1.4 ml/min per kg) respectively. However, fetal MCR was significantly increased. Term was 145 days. Metabolic clearance rate was 15.5 +/- 1.7 at 110-125 days of gestation, 25.6 +/- 2.9 at 126-135 days, 29.7 +/- 4.9 at 136-145 days and remained raised in the first 2 weeks post partum. Gastrin did not cross the placenta in either direction. Placental destruction of gastrin was not responsible for the increased fetal MCR as umbilical artery and umbilical vein levels were not significantly different during fetal gastrin infusion. Furthermore, MCR remained raised in the newborn lambs. Gastrin PR was significantly increased at all ages. The results showed that the previously reported fetal hypergastrinaemia is from fetal sources and is not a result of immaturity of clearance mechanisms. In fact, fetal MCR was significantly increased. The increased fetal plasma gastrin levels are due to an increased rate of production from the fetus.
Although gastrin is found in adult gastric juice, rapid enzymatic destruction by pepsin in the acid environment makes a physiological role in the adult unlikely. Gastric pH in the fetal sheep is neutral so that gastric juice gastrin could be present, and if present, have a physiological function. The aim of this study was to determine the presence, molecular forms and metabolism of gastrin in gastric juice. Gastrin was present in fetal gastric juice at significantly higher concentrations than in fetal plasma. The majority of gastric juice gastrin was present as the biologically active gastrin-17. Gastrin was stable in normal fetal gastric juice, but was rapidly metabolized to smaller C-terminal fragments when the gastric juice was acidified. With the known growth promoting effect of gastrin on gastrointestinal mucosa, gastrin in fetal juice could have a unique role in the in utero development of the gastrointestinal tract.
In the term human and ovine fetus, plasma gastrin is elevated, but gastric acid secretion is below adult levels, suggesting a developmentally related immaturity in gastrin and gastric acid regulation. This study investigated a number of elements of the gastric acid regulatory system: gastrin and its glycine-extended precursor, somatostatin, and the H+/K(+)-ATPase. Measurements were made in blood, antrum, and fundus of the ovine fetus during the last half of gestation, of 15-day-old lambs, and of adult sheep at the level of mRNA synthesis, tissue storage, and secretion. Plasma amidated gastrin (gastrin-amide) was elevated at or above adult values from 125 days (term is 145 days) and steadily increased with development, peaking in the lamb. Similar changes occurred with plasma glycine-extended gastrin (gastrin-gly). The peak concentration of antral gastrin-amide was present in the lamb, while the maximum antral gastrin-gly level occurred 1 week before birth. Gastrin mRNA paralleled the changes in antral gastrin-gly. The proportion of higher mol wt species of gastrin decreased during gestation in both plasma and antrum. Low amounts of mRNA for the H+/K(+)-ATPase was present from at least 120 days of gestation and antedated gastric acid secretion. However, there was a 3-fold increase in H+/K(+)-ATPase mRNA from the 140-day-old fetus to the lamb, the period when the greatest reduction in gastric pH occurred (pH 5 to 2). Antral and fundic somatostatin increased rapidly in the fetus at 120 days gestation and were above adult values at term and in the lamb. Somatostatin mRNA changed in parallel to somatostatin peptide. Somatostatin-14 was the major species in antrum and fundus throughout development. The increase in circulating and antral gastrin-amide after birth may be the result of increased amidation of gastrin-gly as well as increased expression of gastrin mRNA. Amidation of gastrin may be a regulatory step in the production of biologically active gastrin during development. The major increase in gastrin and the H+/K(+)-ATPase that occurs in the week before and after gestation correlated with the onset of increased gastric acidity.
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