Epidermal growth factor (EGF) is known to induce fetal lung maturation and its receptor is present in the lungs of several species. Recently, EGF has been immunolocalized in type II pneumocytes in rat lung. We postulated that EGF is synthesized in type II pneumocytes and that, because of its position-restricted distribution within the alveolus, EGF might act as an autocrine regulator of type II pneumocyte function. Herein, we have tested the hypothesis using adult rat type II pneumocytes in primary culture. In situ hybridization, using an oligonucleotide probe corresponding to amino acid residues 1070 to 1081 of mouse EGF precursor, demonstrated the presence of EGF precursor mRNA. Upon S-200 Sephacryl gel chromatography of type II pneumocyte extracts, EGF-reactive protein eluted as a high-molecular-weight form (greater than 100 kD). EGF immunoreactivity was localized within type II pneumocytes in the periphery of groups of 10 to 15 cells in culture. The type II pneumocytes bound [125I]EGF in a specific manner, indicating the presence of EGF receptors. Scatchard plots gave an apparent affinity constant (Ka) of 1 x 10(9) liters/mol, and the number of receptors was estimated to be 4.8 x 10(11) mg protein (50 per cell). EGF receptor binding specificity was confirmed by the absence of an autoradiographic signal for cells incubated in the presence of a 100-fold excess concentration of transforming growth factor-alpha. Binding of [125I]EGF could also be downregulated 95% by incubation with 0.2 nM transforming growth factor-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

[MJ.] trols, To study possible alterations in EGF binding, 12sI-EGF was injected i.v. in newborn rats. 12sI-EGF bound in all the organs investigated. The binding is listed in decreasing order: liver, gut, skin, kidney, and lungs. In the pups from EGF-immunized rats, the lungs and the skin bound a significantly higher amount than the controls. This could represent an upregulation of the EGF receptor in response to the lack of EGF. Postnatally, the pups from EGF-immunized mothers grew faster and were on par with controls within 1 wk. We found no differences concerning tooth eruption, ear opening, and eye opening. In extension of present knowledge concerning the tissue localization of EGF and its receptor and concerning the pharmacologic effects of EGF, our study demonstrates an effect of EGF deficiency. This supports a role for EGF in the epigenetic regulation of the development of the lungs, the skin, and the liver. (Pediatr Res 37: 175-181, 1995) Abbreviations EGF, epidermal growth factor SP-A, surfactant protein A TGF-a, transforming growth factor-aWe have used rats with epidermal growth factor (EGF) autoantibodies to study the role of EGF deficiency during perinatal development. The study was focused on organs known to contain EGF or its receptor. Compared with controls, the offspring of autoimmune rats had a higher perinatal mortality and a lower birth weight. The weight of the lungs was particularly low in the offspring of EGF-immunized rats, and morphologically the lungs from the surviving pups seemed atelectatic and had alveolar duct dilatation, which indicates mild respiratory distress syndrome. Judged from immunohistochemical studies, the amount of surfactant protein-A was decreased, suggesting a delayed lung maturation. The offspring of EGF-immunized rats had dry and wrinkled skin. The skin was thin and the hair follicles were immature. This suggests a role for EGF in the growth and development of the skin. The liver/body weight ratio was lower in pups from EGF-immunized rats. This difference was, however, not significant (p = 0.07), but flow cytometric analyses showed a significantly lower proportion of the liver cells from newborn EGF-deficient pups to be in S-phase and indicated that these cells were larger than liver cells from conThe epigenetic regulation of fetal and neonatal development is assumed to take place within a milieu of growth factors. This hypothesis is mainly deduced from the localization of growth factors and growth factor receptors and from studies of their pharmacologic effects. Limited information is available about the effects of growth factor deficiency. Based on studies in which EGF has been injected into the mother, the fetus, or the neonate, EGF is believed to be involved in the development of the integument (1, 2), the lungs (3, 4), the liver (5), and the digestive tract (6). At present it has not been established whether these effects reflect a physiologic or a pharmacologic role of the peptide. One of the difficulties faced is that EGF is produced in multiple organs...

The tissue localisation and time of first appearance of Epidermal Growth Factor (EGF) in the developing rat were investigated by means of immunohistochemistry, radioimmunoassay and radioreceptor assay. In this study we were able to show, that EGF appears prenatally in the lung and the kidney from gestational day 19. Postnatally EGF was found also in the gastrointestinal tract, first in Brunner's glands of the duodenum (at birth), next in the Paneth cells (day 7), and finally in the submandibular glands (day 25). The immunohistochemical and radioreceptor results are consistent, whereas the radioimmunoassay detects EGF later and in smaller quantities, than does the radioreceptor assay. These differences will be discussed.

Pancreatic spasmolytic polypeptide (PSP) is a peptide that is isolated from the porcine pancreas and that affects intestinal motility and growth of intestinal tumour cells in vitro. The peptide was recently demonstrated to be present in large amounts in pancreatic juice. The cellular origin of the peptide, however, is largely unclarified and the localization was therefore studied of PSP in pigs using immunohistochemistry. Positive immunoreactions were seen in the pancreas, the stomach, the duodenum, the jejunum and the ileum. In the pancreas, the PSP immunoreaction was seen in all acinar cells; no immunoreaction was seen in the endocrine islets. In the stomach, it was localized to the mucous cells of the glands in the cardiac gland region, the corpus and the pylorus. In the duodenum a strong immunoreaction was present in Brunner's glands and in the cells of their excretory ducts. In the jejunum and ileum, PSP immunoreactivity was seen in some of the cells in the epithelium of the crypts of Lieberkühn. A peptide chromatographically identical to highly purified PSP was identified in pancreas and stomach extracts. Thus epithelial cells in all parts of the stomach and small intestine contribute to the supply of PSP to the gut lumen.