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Bile from rats of different ages (suckling 10-12 days; weanling 30-33 days, and adult 60-70 days) was collected and studied for the presence of immuno- and receptor-assayable insulin-like growth factor-II (IGF-II) concentrations. Concentrations of RIA IGF-II in bile were highest in suckling rats (230 +/- 38 ng/ml) and lowest in adults (47 +/- 7 ng/ml). These concentrations were approximately twice those of the bile IGF-I concentration in sucklings, as measured in a previous study. Selected bile samples were also assayed using a competitive binding assay with a crude preparation of adult rat liver membranes bearing the IGF-II receptor. These studies confirmed the presence of receptor- (as well as immuno-) active IGF-II in bile. Since bile flow rates increased dramatically after the suckling period, bile delivery rates of IGF-II were normalized as picograms per gram body weight per hour. When such calculations were done, bile IGF-II delivery rates to the small intestine were highest in sucklings and weanlings in comparison to adult rats. Thus non-enterically derived (milk- and bile-borne) IGF-II delivery to the suckling small intestine can be approximated at roughly 1 microg/day. Unlike IGF-I, intravenously injected IGF-II could not be detected in suckling bile, suggesting a predominantly hepatic origin. From this study we conclude that there exists a significant delivery of receptor-active IGF-II to the gastrointestinal tract of rats of all ages., (Copyright 2000 S. Karger AG, Basel)

Small amounts of lactose have been shown to be absorbed intact across the intestine and excreted unchanged in the urine of newborns and adults. We designed a study to quantitate the intestinal uptake and urinary excretion of this disaccharide in these age groups. Similar amounts of lactose were given orally to 17 term newborns (age: 24.8 +/- 3.0 h) as a standard infant formula, and to 15 adult lactose absorbers (age: 28.1 +/- 2.6 years) and 11 adult lactose malabsorbers (age: 24.7 +/- 2.9 years) as a 20% water solution. Following lactose ingestion, breath was collected every 30 or 60 min for 3 h and analyzed for hydrogen concentration. Urine was also collected, and lactose and creatinine concentrations were determined. Peak hydrogen concentration was less than 20 ppm above baseline in newborns and adult lactose absorbers and 85 +/- 14 ppm in adult lactose malabsorbers. Urinary lactose excretion, expressed as a function of body weight (mg/ml/kg b.w.), was substantially greater in newborns (4.2 +/- 0.82) than in adult lactose absorbers (0.29 +/- 0.07; p less than 0.001) and adult lactose malabsorbers (0.55 +/- 0.04; p less than 0.01). Similarly, urinary lactose excretion expressed as a ratio of urinary lactose to urinary creatinine (mg/mg) was increased (p less than 0.001) in newborns (2.05 +/- 0.26) when compared to adult lactose absorbers (0.11 +/- 0.02) and adult lactose malabsorbers (0.20 +/- 0.02). Our data demonstrate that the intestinal uptake and urinary excretion of intact lactose is significantly increased in newborns compared to adult subjects.

Four acid glycosidases have been studied in the colon from developing rats: beta-N-acetylglucosaminidase, beta-galactosidase, alpha-fucosidase, and beta-glucuronidase. These four enzymes exhibit substantial changes in specific activity during maturation from fetus to adult. Further, the location of maximal enzyme activity changes from proximal to distal colon during development. Whereas 1- to 8-day-old suckling rats exhibited higher enzyme specific activities in the proximal than in the distal colon (1.2- to 4.9-fold higher), the adult rat colonic glycosidases always were higher in specific activity in the distal than in the proximal colon (1.2- to 1.3-fold higher, except 1.9-fold higher for beta-N-acetylglucosaminidase). The gradient of enzyme activity along the colon length changed more in sucklings than in adults. Whereas the activity only varied 1.3- to 3.0-fold along the length of the adult rat colon, variation of 2.3- to 10-fold occurred in different segments of the suckling rat colon.

Suckling (12- to 14-day-old) and weanling (30-day-old) rats were sacrificed 2 h after oral administration of 3H-labeled prostaglandin F2 alpha. Although radioactivity recovered from the stomach and small intestine (including contents) was slightly higher in sucklings (28.3 +/- 3.7%; n = 10) than in weanling rats (21.3 +/- 5.3%; n = 7), the liver of sucklings contained significantly higher amounts of counts (11.0 +/- 1.1 vs. 3.3 +/- 0.5%). Combined column and thin-layer chromatography of liver extracts showed more authentic prostaglandin F2 alpha in sucklings (11.0 +/- 0.5% of the liver counts) than in weanlings (7.0 +/- 1.1%). The liver of suckling rats contained a higher percentage of more polar metabolites (43.3 +/- 1.6 vs. 34.3 +/- 3.0%). These studies demonstrate differences in processing of oral prostaglandin F2 alpha in the early postnatal period.

Administration of high doses of triiodothyronine (T3) for 4 days to lactating rats evokes an increase in T3 levels in their sera and milk, as well as in the sera of pups suckled by them. Thyroid-stimulating hormone levels in sera of mothers and sucklings are decreased. Suckling rats of T3-treated mothers exhibit a precocious increase in the activity of jejunal sucrase and maltase as well as in activity of several liver acid beta-glycosidases.

Male rats were weaned normally (NW; day 30 after birth) or prematurely (PW; day 18) to a Purina Chow diet. Serum cholesterol levels and the activities of some enzymes of fatty acid and glucose metabolism were determined when the animals were 6 and 10 months old and, in the older group, also after 2 days of starvation. Blood cholesterol levels rose with age and at 10 months were higher in PW than NW rats. This difference disappeared after starvation. Hepatic pyruvate kinase (PK) activity was the same in fed NW and PW animals but was significantly higher in starved PW than NW rats. Hepatic phosphoenolpyruvate carboxykinase (PEPcK) activity was lower in NW than in PW rats, but this difference disappeared on starvation. In white fat, starvation caused a fall in PEPcK activity in both groups. In general, the effect of starvation did not accentuate the differences between the two groups. However, PEPcK activity in white fat increased with age about fourfold.

Because previous measurements of early postnatal, small intestinal fluid, proteolytic activity in man and animals have been contradictory, we characterized the development of luminal protein digestion using a sensitive assay in which iodinated bovine casein was incubated in vitro at 37 degrees C with luminal fluid flushed from the stomach and small intestine of 12-day-old suckling and 31-day-old weanling rats, followed by measurement of radioactivity in trichloroacetic acid-soluble material. Gastric proteolysis at pH 3.2 in the weanling rat was approximately 50-fold greater than that in the suckling rat. Analysis of stomach fluid acid-soluble casein degradation products of weanling rats by chromatography on G-50 Sephadex in the presence of sodium dodecyl sulfate revealed three peaks of radioactivity comprising 65, 18 and 12% of the total product in order of elution. In the jejunum at neutral pH, the proteolytic capacity of the weanling rat was approximately five times that of the suckling rat; such differences were more pronounced in the ileum, however, in which protein hydrolysis of weanling rats was 30-fold higher than that in the suckling rat. In the suckling rat, small intestine proteolytic activity was greater in the jejunum than in the ileum, but in the weanling rat greater protein hydrolysis was present in the ileum. Gel filtration analysis of reaction products in both intestinal segments and at both ages demonstrated two peaks, which constituted 60-70 and 15-23% of the acid-soluble material in order of elution.(ABSTRACT TRUNCATED AT 250 WORDS)

Jejunal and ileal segments from preterm rat fetuses were implanted under the kidney capsula of adult rats. Sucrase, lactase and acid beta-galactosidase activities were determined in the isografts at different times after implantation, and in corresponding segments developing in situ. Whereas fetal intestine contains considerable activity of acid beta-galactosidase and lactase, no sucrase activity is detectable. Similarly -- as in situ -- 4 weeks after the implantation the jejunal segment exhibited higher activity of sucrase and lactase than the ileal segment. Acid beta-galactosidase was more active in ileal than in jejunal segments -- both growing in situ as well as isografts. Experiments have thus demonstrated that the expression of the jejunoileal gradient of activity of the 3 enzymes studied does not depend on direct contact with food or gastric, pancreatic and biliary juices. This gives validity to the suggestion that the gradient may already be programmed in fetal intestinal tissue, but other factors active in situ might be responsible for its magnitude.

Although stress during the perinatal period may influence a number of enzymes in the gastrointestinal tract, the resulting effects on digestive processes are not completely understood. In suckling rats, corticosteroid administration increases levels of proteases in gastric mucosa and pancreas, but previous studies of unstimulated luminal fluid proteolytic activity suggest no effect. To re-evaluate this phenomenon, we injected suckling rats with cortisone acetate (5 mg/100 g body weight) subcutaneously daily on days 9-11 followed by sacrifice on day 12; littermates served as controls. Luminal fluid from stomach and small intestine was analyzed for proteolytic activity by a sensitive assay in which incubation in vitro with 125I-bovine casein was followed by measurement of radioactivity soluble in trichloroacetic acid. Cortisone acetate produced significant increases in luminal proteolytic activity in all gastrointestinal segments with the most dramatic effect observed in the ileum; this segment showed a more than 10-fold enhancement of proteolysis with steroid treatment. Analysis of acid-precipitable reaction products by electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate also revealed enhancement of casein degradation by luminal fluid in all segments from steroid-treated animals. We conclude that corticosteroid increases luminal proteolysis in the gastrointestinal tract of the suckling rat. This phenomenon may have implications for steroid-induced premature closure to macromolecular absorption and protein digestive capacity during the perinatal period.

Prostaglandins are present in breast milk and may protect and maintain intestinal epithelial cell integrity in developing mammals. In view of their very short half-life in other body tissues and fluids, studies were performed to determine prostaglandin stability in milk and gastric fluid. Tritiated prostaglandins E2 and F2 alpha were incubated for 30 min in whole milk, milk cells, and milk plasma obtained from mothers delivering at term and prematurely, and in preterm infant gastric fluid. Radioactivity chromatographic analysis revealed minimal degradation of PG in milk preparations and gastric fluid. Thus, milk may serve as an effective natural medium for PG delivery to the gastrointestinal tract. The cytoprotective effect of prostaglandins on the gastrointestinal tract may be related to their stability and lack of degradation in milk and gastric digestive juices.