Epidermal growth factor influences cell proliferation, glycoproteins, and lipase activity in human fetal stomach.

BACKGROUND & AIMS: The role of epidermal growth factor (EGF) in the functional development of human stomach is unknown. The aim of this study was to establish the distribution and cellular localization of EGF receptors in developing gastric mucosa and to determine the effects of EGF on epithelial cell proliferation and differentiation. METHODS: Quantitative radioautography with 125I-EGF and indirect immunofluorescence using an antibody for human EGF receptor were performed using fetal gastric tissues (12-20 weeks of gestation). The effects of EGF (1, 10, and 100 ng/mL) on DNA synthesis, glycoprotein synthesis, and lipase and pepsin activities in fetal gastric explants maintained in serum-free organ culture were determined. RESULTS: EGF receptors were present as early as 12 weeks of gestation and localized on basolateral membranes of all gastric epithelial cells. DNA and glycoprotein synthesis were significantly increased after 24 hours of culture in the presence of EGF. Unlike pepsin activity, lipase activity was modulated by EGF, and a significant diminution of the tissue lipolytic activity was noted after 5 days of culture. CONCLUSIONS: This study clearly indicates the influence of EGF on the proliferation and differentiation of gastric epithelium, suggesting an important role for EGF in fetal development of the human gastric mucosa.

Ontogeny of human gastric lipase and pepsin activities.

BACKGROUND/AIMS: The developmental profile of human gastric lipase activity as well as the secretory capacity of the immature gastric mucosa are still unknown. The aims of this study were to establish tissue activity levels for lipase and pepsin in the various anatomical regions of the developing stomach and to assess whether lipase is secreted by the fetal gastric mucosa. METHODS: Lipase and pepsin activities were assayed in 49 specimens of different gestational ages. Gastric explants were cultured in chemically defined medium for up to 5 days, and enzymic activities were measured in tissues and in the culture media. RESULTS: Lipolytic activity was present in gastric tissues at 10-13 weeks and steadily increased for up to 20 weeks, whereas pepsin activity did not vary significantly over the periods of study. There was a clear decreasing gradient of lipase activity; the highest activity was in the fundic area, and the lowest activity was in the antrum. Quantitative pepsin activity did not vary over the gastric regions. During culture, total lipolytic and pepsin activity increased 3.8-fold, and both enzymes were secreted into the culture medium. CONCLUSIONS: Gastric lipase appears as early as 10-13 weeks. Adult distribution of the enzyme became established by 16 weeks' gestation. The secretion of lipase into the organ culture suggests that the gastric mucosa is the main source of lipolytic activity in gastric aspirates of premature infants.

Maturation of human fetal stomach in organ culture.

BACKGROUND: This investigation was undertaken to establish a serum-free organ culture technique allowing for the morphological and physiological maintenance of human fetal stomach in vitro. METHODS: Explants from gastric corpuses (12-17 weeks of gestation) were cultured in serum-free medium for periods of up to 15 days. RESULTS: After 15 days of culture, surface mucous cells were more mature, gastric glands were numerous and well developed, and all epithelial cell types were morphologically very well preserved. Morphometric measurements of the glands revealed an accelerated development in culture compared with that found in utero. Even though the incorporation of [3H]thymidine into total DNA decreased, the labeling indices determined by radioautography confirmed that epithelial cell proliferation was maintained especially in the pit/neck portion and at the base of the glandular compartments. A significant increase in total glycoprotein synthesis, as evaluated by the incorporation of [3H]glucosamine, was observed and correlated with the differentiation of the mucous cells. CONCLUSIONS: This investigation establishes for the first time that human gastric mucosa can be maintained up to 15 days in organ culture and that maturation of the gastric mucosa can be reproduced in chemically defined media.