Maturation and differentiation of cultured fetal stomach. Effects of corticosteroids, pentagastrin, and cytochalasin B

Gastric mucosa of fetal rats undergoes striking developmental changes during the last few days of gestation in utero. To investigate some aspects of this process, gastric explants from 18-day fetuses (4 days before birth) were maintained in organ culture for 3 days, then assessed by light and electron microscopy. The epithelia from base line uncultured stomachs were stratified and morphologically undifferentiated. During culture in basic medium (Leibovitz L 15), modest maturation of antral and fundic architecture occurred, characterized by epithelial invagination to produce small pit-glands. Secretory granules appeared in occasional epithelial cells, and cytochemistry indicated that most were mucous granules. Addition of pentagastrin (10(-9) to 2 X 10(-7) M) did not induce further morphological maturation in this system. However, addition of cortisol (10(-6) to 10(-5) M) resulted in a marked, dose-related increase of pit-gland formation and of cytological differentiation (appearance of secretory granules). This cortisol-induced architectural maturation was completely inhibited by the mold metabolite cytochalasin B (10(-5) M). The results indicate that fetal gastric maturation can be partially reproduced by culture in chemically defined media, and also suggest that corticosteroids may plan an important role in gastric organogenesis.     

Lysosomal cysteine and aspartic proteinases and ubiquitin in rat and human urinary bladder epithelium

To examine localization of cysteine and aspartic proteinases, and ubiquitin in rat and human urinary bladders, immunocytochemistry was applied to the tissues. In semi-thin sections, immunoreactivity for cathepsins B and D was densely localized throughout epithelial layers of rats and humans, while that for cathepsins H and L was mainly localized in rat superficial and human intermediate cells. Immunoreactivity for cathepsin C was relatively high in rat and human epithelia, especially in humans. Immunoreactivity for ubiquitin was detected in rat and human epithelial cells. By electron microscopy, vesicular or heterogeneously dense lysosomes labeled with immunogold particles indicating cathepsin B were seen in rat and human epithelial cells; particularly, they often appeared near fusiform vesicles in rat superficial cells and in human intermediate and superficial cells. By double immunostaining, lysosomes with or without vesicular structures were co-labeled with immunogold particles showing both cathepsin B and ubiquitin. The results suggest that cathepsins B, C, H, and L, and cathepsin D are involved in the lysosomal system of rat and human bladder epithelia. Moreover, considering that ubiquitin is a cofactor in the soluble ATP-dependent proteolysis, the results may also indicate that epithelial cells actively form autophagolysosomes.     

Changes in pulmonary calcitonin gene-related peptide and protein gene product 9.5 innervation in rats infected with Mycoplasma pulmonis

Epithelial-mesenchymal interaction is a prerequisite for tooth morphogenesis. To study this interaction, inner enamel epithelium and dental papilla mesenchyme of molar tooth germs from a 16.5-day mouse embryo were dissociated enzymatically and cultured alone or after recombination. Characteristic matrix protein synthesized and secreted by recombined tooth germ was determined quantitatively by enzyme-linked immunosorbent assay. The protein was detected in the culture of recombined tooth germ but not of dissociated enamel epithelium alone. The amount of enamel protein increased until 8 days in culture. Morphological differentiation of the recombined epithelial rudiment into ameloblasts and enamel protein production were confirmed.     

Impact of assertive community treatment on homeless persons with co-occurring severe psychiatric and substance use disorders

To investigate the possibility of engrafting fetal liver hematopoietic cells by in utero intraperitoneal transplantation, we transplanted donor cells obtained from mouse fetuses at 13, 15 and 17 days of gestation to mouse fetuses at 15, 16 and 17 days of gestation. Engraftment was assessed by Sry gene amplification of DNA extracted from peripheral blood samples of transplanted mice six weeks after birth. In comparison, we performed an in vitro colony-assay of fetal liver cells at 13, 15, and 17 days of gestation. The incidence of engraftment was significantly higher in cells of 15 days of gestation than in cells of 13 or 17 days of gestation, whereas the colony forming activity decreased gradually from 13 to 15 days of gestation. From these results, we suggest that the 15 day liver contains hematopoietic progenitors which have the specific characteristics required for engraftment by intraperitoneal transplantation.     

Suppressive effect of fetal testes on development of fetal ovaries transplanted into adult males in the rat

The age-related testicular effect on the ovarian primordia was studied by combined transplantation of fetal testes and ovaries in adult male hosts. First, ovarian primordia of 14-day fetal rats were transplanted into a renal subcapsular position of castrated or intact adult male rats. In both the castrated and the intact hosts, most of the ovarian transplants developed normally with only 3 of them having in part seminiferous tubule-like structures in addition to normal ovarian structure. Second, a 14-day ovary was combined with a fetal testis the age of which varied from 13- to 18-day, and the combination was transplanted. In the combination of a 14-day ovary and a 13-day testis, the results varied in such a way that the ovary or the testis alone developed or otherwise, both gonads developed well. In union with 15- to 18-day testes, the ovaries did not develop, although the testes developed well. These results suggest that the 14-day ovarian primordia have a slight reactiveness to androgens of host rats and that the 13-day fetal testes begin to inhibit the development of the 14-day ovaries co-transplanted with them.     

Immunocytochemical localization of the NPY/PYY Y1 receptor in the developing pancreas

Neuropeptide Y, peptide YY, and pancreatic polypeptide are structurally related peptides that are considered to play a role in the regulation of pancreatic secretion and blood flow. Several receptor subtypes for these peptides have been identified, and the Y1, Y2, Y4/PP1, Y5, and Y5/PP2/Y2b receptors are cloned. We have prepared polyclonal peptide antibodies that recognize the Y1 receptor and now report on its localization in the adult and developing rat pancreas. In the adult pancreas, Y1 receptors were detected both in some centroacinar and intralobular duct cells and in endothelial cells. In the developing pancreas (E12.5-E16.5), Y1 receptor immunoreactivity was observed in numerous nonendocrine epithelial cells. These cells occurred in the immediate vicinity of peptide YY-positive endocrine cells. At E16.5, a fraction of these Y1 receptor-containing cells co-stored amylase. One day later, Y1 receptor immunoreactivity became restricted to pancreatic duct-like cells that occurred in close proximity to peptide YY cells. In fetal rats, intense Y1 receptor staining was also observed in endothelial cells. These observations, together with the finding of early pancreatic peptide YY expression, suggest that peptide YY produced by fetal endocrine cells may exert an action on exocrine cells, duct cells and endothelial cells during development.     

Two-day quadruple therapy for cure of Helicobacter pylori infection: a comparative, randomized trial

PURPOSE: Small intestinal transplantation remains a significant clinical problem. Allogeneic fetal intestinal (AFI) transplantation shows promise, particularly regarding procurement; however, no studiesto date have evaluated the potential success of true allogeneic loci implantation. The authors hypothesized that isolated segments of AFI could be heterotopically transplanted but would require immunosuppression to survive. METHODS: Donor tissue was obtained from late-gestation Brown Norway rat fetuses with a histo-locus RTN and Fischer fetuses with a histo-locus RT1L. The recipients were adolescent male Fischer rats with a histo-locus RT1L. A 1.2-cm segment of fetal small bowel was implanted in the omentum of the recipient rat and allowed to mature for 5 weeks. Animals were then separated into five groups. Group A served as controls with syngeneic fetal intestinal (SFI) transplant. Group B received AFI with no immunosuppression; group C, AFI transplant with five days of FK506; group D, AFI with 10 days of FK506; and Group E, AFI with daily FK506 for the entire 5-week maturation period. Animals were killed on day 35. RESULTS: All animals gained weight over the maturation period. Groups B, C, and D had no viable transplant segments at day 35. Groups A and E both had well-developed viable segments confirmed by gross and histological evaluation. CONCLUSIONS: FK506 allows for normal intestinal development for use in allogeneic fetal bowel transplantation. With this observation, the use of fetal intestine transplanted into the portal circulation emerges as a potentially viable alternative to present intestinal transplant models.     

Transplanted and repopulated retinal pigment epithelial cells on damaged Bruch's membrane in rabbits

AIMS: The authors studied how artificially damaged Bruch's membrane influenced growth and differentiation of transplanted embryonic retinal pigment epithelial (RPE) cells and of host RPE cells in rabbits. METHODS: Embryonic RPE cells obtained from pigmented rabbits were transplanted into the subretinal space of adult albino rabbits. The host RPE was removed with a silicone cannula, and Bruch's membrane was damaged by scratching with a microhooked 27 gauge needle under the detached retina in closed vitrectomy. The transplantation sites were examined 3, 7, and 14 days after surgery by light and electron microscopy. RESULTS: Varying degrees of damage in Bruch's membrane were observed. Pigmented and hypopigmented RPE cells showed a normal polarity and tight junctions were seen at the sites of mild to moderate damage 3-7 days after the surgery. In contrast, fibroblast-like cells with no such features of RPE cells formed multiple layers at the sites of severe damage involving the full thickness of Bruch's membrane and the choriocapillaris even 14 days after the surgery. Without transplantation, host RPE cells repopulated the damaged areas in the same way as transplanted RPE cells. CONCLUSIONS: Transplanted embryonic RPE cells as well as host RPE cells grew and differentiated on the moderately damaged Bruch's membrane, while the severely damaged Bruch's membrane did not allow differentiation of RPE cells although these cells could grow and cover the damaged areas.     

Relationship between epithelial and connective tissues in the stomach of the frog Rana temporaria during metamorphosis: an ultrastructural study

In the course of metamorphosis of the stomach of Rana temporaria tadpoles there is a marked increase in the amount of active mesenchymal fibroblasts and extracellular matrix underlying the regenerating gastric epithelium. At the onset of metamorphosis, a thick PAS-positive basement membrane is developed around the epithelial component of the mucosa, formed by the apical, degenerating larval epithelium and the basal, regenerative epithelial cords. Under the electron microscope, a folded basement membrane is usually revealed under the apical degenerating epithelium while a compact basement membrane (up to 1-2 microns thick), forming both patches and more extensive areas, is frequently seen around the regenerative glandular cords. Cytoplasmic processes, extending from both the epithelial and mesenchymal fibroblastic cells, cross the basement membrane and make physical contact between the two cellular types. At mid-metamorphosis areas of thick PAS-positive basement membrane are still observed around the differentiating glandular outlines, before disappearing completely at late metamorphosis. The probable involvement of intertissue interactions between epithelium and connective elements in the morphogenesis, proliferation and differentiation of secondary, definitive frog stomach is discussed. Early contacts between epithelium and phagocytes, probably related to the invasion of epithelium by the phagocytic cells, have also been observed.     

Immunocytochemical localization of transforming growth factor alpha, epidermal growth factor and epidermal growth factor receptor in the cat endometrium and placenta

Hoxb-5 is one of the few homeobox genes strongly expressed in the developing mouse lung. To explore the hypothesis that Hoxb-5 acts to regulate epithelial cell fate and branching morphogenesis in the developing lung, we studied the temporal, spatial, and cell-specific expression of Hoxb-5 from gestational day (d) 13.5 to postnatal day (P) 2. Immunocytochemistry demonstrated regional localization of Hoxb-5 protein to developing conducting airways and surrounding mesenchyme. The cellular expression pattern changed from diffusely positive nuclei of mesenchymal cells on d13.5 to become more localized to nuclei of subepithelial fibroblasts and some adjacent columnar and cuboidal epithelial cells on d14.5. After d14.5, Hoxb-5 protein expression continued to decrease in mesenchymal cells distal from developing airways, but persisted in fibroblasts underlying conducting airways. Hoxb-5 protein expression persisted in nuclei of columnar and cuboidal epithelial cells on d16.5 and d17.5, with expression in low cuboidal epithelial cells as well from d17.5 to P2. Western blot analysis showed temporal and quantitative changes in Hoxb-5 protein expression with peak expression on d14.5-15.5. We conclude that Hoxb-5 protein is developmentally regulated in a temporal, spatial, and cell-specific manner throughout the pseudoglandular, canalicular, and terminal saccular periods of lung development in the mouse. This localization and expression pattern suggests that Hoxb-5 may influence branching morphogenesis, cell-cell communication, cell fate, and differentiation of conducting airway epithelia.     

Dirofilaria immitis: experimental infection of rabbits with immature fifth-stage worms

To establish an animal model for human pulmonary dirofilariasis, we experimentally infected nine rabbits with immature fifth-stage worms of Dirofilaria immitis. The rabbits were infected by subcutaneous transplantation with various numbers of immature worms collected from 110- and 120-day-old infections of dogs. Four of seven rabbits infected with up to four larvae possessed encapsulated worms in the lungs at 196 or 308 days post-transplantation. Two rabbits transplanted with eight worms died of pulmonary hemorrhagic infarction 18 and 28 days post-transplantation. Marked histopathologic changes were observed in the lungs at the site of degenerating worms, which were encapsulated by a fibrous wall. Severe to mild infiltrations with eosinophils, heterophils, lymphocytes, plasma cells, and histiocytes were found in granulomas and their surrounding areas. The findings in these rabbits resemble those reported for human cases of pulmonary dirofilariasis.     

Antibiotic susceptibility among aerobic gram-negative bacilli in intensive care units in 5 European countries. French and Portuguese ICU Study Groups

BACKGROUND: Many successful pigment epithelium transplantation studies involving pink-eyed Royal College of Surgeons (RCS) dystrophic rats showed highly pigmented transplanted cells forming a double layer with slightly pigmented cells, attached to Bruch's membrane. Since it is not clear whether transplanted pigmented cells can displace retinal pigment epithelial (RPE) host cells from Bruch's membrane, we suggested that RPE cells of RCS dystrophic rats can phagocytize melanin granules, possibly derived from perished transplanted cells. METHODS: In a series of three experiments, RPE cells of nine pink-eyed, 2 1/2-month-old RCS dystrophic rats were isolated by trypsinization and mechanical dissection and cultivated in Dulbecco's modified Eagles' medium. These cells were then fed with melanin granules, isolated from bovine RPE cells, double-trypsinized after phagocytosis and viewed by light and electron microscopy. We also transplanted iris pigment epithelial (IPE) cells of 20-day-old Long-Evans rats into the subretinal space of pink-eyed RCS dystrophic rats of the same age, shown in light-microscopic photography after 42 days. RESULTS: Living RPE cells were heavily pigmented after feeding with isolated melanin granules in all three experiments as viewed by light microscopy. In addition, we identified melanin granules phagocytized by dystrophic RPE cells in electron microscopy. After transplantation of pigmented IPE cells into the subretinal space of pink-eyed RCS dystrophic rats' eyes, a layer of slightly pigmented cells was seen on Bruch's membrane below the transplanted IPE cells, shown in light microscopy. CONCLUSION: We have shown by phagocytosis assay that dystrophic RPE cells can take up melanin granules in vitro. Our results assume that pigmented cells in transplantation studies, found as a monolayer, attached to Bruch's membrane, cannot automatically be identified as transplanted cells. Instead, the possibility of perished transplanted cells serving as melanin donors for RPE host cells must be taken into consideration.     

Humoral immune responses to cathepsin D and glucose-regulated protein 78 in ovarian cancer patients

Many cancer patients develop tumor-reactive immune responses against antigens that are either expressed on the surface of tumor cells or released from them into the peripheral circulation. In this study, tumor-reactive immunoglobulins, present in the sera of ovarian cancer patients, were used to identify commonly recognized tumor-associated antigens on ovarian tumor cells. Western immunoblot analysis of cellular proteins, obtained from UL-1 ovarian tumor cell line, demonstrated several commonly recognized immunoreactive proteins. Two of these proteins (Mr 32,000 and 71,000) were selected for further investigation. Cellular proteins isolated from normal human ovarian epithelia, in a similar fashion, failed to exhibit corresponding immunoreactivity to these proteins. As an additional control, sera from normal (nontumor-bearing) individuals failed to identify these proteins on Western immunoblots. Furthermore, the absorption of the ovarian cancer patients' sera with normal ovarian epithelial tissue did not remove the reactivity of these two proteins. The Mr 32,000 and 71,000 proteins were subsequently purified by reverse-phase high-performance liquid chromatography, separated by SDS-PAGE, transferred to the polyvinylidene difluoride membrane, and digested with trypsin. These resulting tryptic fragments were separated by microbore reverse-phase high-performance liquid chromatography, and selected fragments were sequenced by mass spectrometry. This sequence analysis identified the Mr 32,000 protein as cathepsin D and the Mr 71,000 as glucose-regulated protein 78 (member of the heat shock protein family). The identities of cathepsin D and glucose-regulated protein 78 were confirmed by Western blot analysis. Additionally, the presence of cathepsin D was demonstrated in association with immune complexes in vivo. Currently, the common antigenic epitopes of these proteins are being defined.     

Thymus transplantation, a critical factor for correction of autoimmune disease in aging MRL/+mice

MRL/MP-+/+ (MRL/+) mice develop pancreatitis and sialoadenitis after they reach 7 months of age. Conventional bone marrow transplantation has been found to be ineffective in the treatment of these forms of apparent autoimmune disease. Old MRL/+ mice show a dramatic thymic involution with age. Hematolymphoid reconstitution is incomplete when fetal liver cells (as a source of hemopoietic stem cells) plus fetal bone (FB; which is used to recruit stromal cells) are transplanted from immunologically normal C57BL/6 donor mice to MRL/+ female recipients. Embryonic thymus from allogeneic C57BL/6 donors was therefore engrafted along with either bone marrow or fetal hematopoietic cells (FHCs) plus fragments of adult or fetal bone. More than seventy percent of old MRL/+ mice (> 7 months) that had been given a fetal thymus (FT) transplant plus either bone marrow or FHCs and also bone fragments survived more than 100 days after treatment. The mice that received FHCs, FB, plus FT from allogeneic donors developed normal T cell and B cell functions. Serum amylase levels decreased in these mice whereas they increased in the mice that received FHCs and FB but not FT. The pancreatitis and sialoadenitis already present at the time of transplantations were fully corrected according to histological analysis by transplants of allogeneic FHCs, FB and FT in the MRL/+ mice. These findings are taken as an experimental indication that perhaps stem cell transplants along with FT grafts might represent a useful strategy for treatment of autoimmune diseases in aged humans.     

Antioxidant systems in rat epididymal spermatozoa

Down-regulation of KAI1 mRNA expression has been shown to be associated with the formation of metastases or disease progression in pancreatic cancer. Whether KAI1 possesses similar characteristics in other malignancies of the gastrointestinal tract is not known. Here, we compared the patterns of KAI1 mRNA expression in 41 esophageal cancers and 35 stomach cancers to assess whether KAI1 might also be of biological relevance in the metastatic ability of these tumors. By Northern blot analysis, KAI1 mRNA levels ranged widely in both normal and cancerous esophageal and gastric tissue samples, with no statistical differences. No association between KAI1 mRNA expression and tumor stage or tumor differentiation was seen in these tumors. In addition, KAI1 mRNA expression was similar in primary esophageal and gastric cancer samples with or without metastases. By in situ hybridization, KAI1 mRNA expression was evident in the cytoplasm of most squamous epithelial cells in the normal esophagus and in nonmucosal epithelial cells of the normal stomach. The staining intensity in the esophageal and gastric cancer cells was similar to that in the normal controls. This differential pattern of KAI1 mRNA expression in esophageal and gastric cancers in comparison to pancreatic cancer indicates that KAI1 seems to influence the potential of gastrointestinal cancer cells to metastasize differently. In esophageal and gastric cancers, the formation of metastases is not dependent on the reduction of KAI1 in the cancer cells.     

Functional defects in lysosomal enzymes in autosomal dominant polycystic kidney disease (ADPKD): abnormalities in synthesis, molecular processing, polarity, and secretion

The phenotype of autosomal dominant polycystic kidney disease (ADPKD) is characterized by basement membrane abnormalities, hyperproliferation, and alterations in epithelial cell polarity. Since proteinases have been implicated in matrix degradation and growth factor activation, lysosomal enzymes were compared in normal and ADPKD tissues and cell cultures. Acidic proteolytic activity (azocasein) was reduced in ADPKD, and specific enzymatic assays detected disease-dependent decreases in the specific activities of beta-galactosidase, beta-hexosaminidase, and cathepsins, B, L, and H. Cathepsin D-specific activities were unchanged. Lucifer yellow fluorescence in ADPKD cells was consistent with an alteration in heterogeneity of lysosomal enzyme content in ADPKD rather than a decrease in total lysosomal number. Western analysis, metabolic labeling, and immunoprecipitation analysis confirmed decreases in the expression and synthesis of the major normal molecular immunoreactive species of beta-galactosidase and cathepsins B and H in ADPKD tissue and cells but no changes in cathepsin D. In addition, ADPKD-specific high-molecular-weight species of cathepsin H were seen and abnormal forms of cathepsin B and beta-galactosidase were common in ADPKD, suggesting abnormal molecular processing and posttranslational modifications. In addition, immunolocalization studies showed abnormal apical plasma-membrane localization of cathepsins B and H in ADPKD cyst epithelial cells, consistent with a protein sorting defect in ADPKD. Increased extracellular secretion of lysosomal enzymes was also measured in ADPKD cultured cells and in filter-grown epithelia shown to be predominantly directed to the basal compartment. These results demonstrate that lysosomal enzyme alterations in ADPKD may play a role in aberrant processing of the basement membrane. Alterations in the polarized secretion of lysosomal enzymes by ADPKD epithelia in vitro were also detected. Whereas all normal epithelia cells secreted lysosomal enzymes predominantly to the apical medium compartments, basally directed secretion was increased in all ADPKD epithelia and attained an overall reversal of polarity for cathepsins B + L. It is concluded that alterations in lysosomal enzyme function in ADPKD are the result of alterations in synthesis, molecular processing, and polarized secretion of specific enzymes and may have impact on proliferative and basement membrane abnormalities in this genetic disease. These results are consistent with a fundamental defect in protein processing sorting, and trafficking in ADPKD.     

Evidence that macrophages are required for T-cell infiltration and rejection of fetal pig pancreas xenografts in nonobese diabetic mice

BACKGROUND: Host macrophages are abundant within fetal pig pancreas xenografts undergoing rejection, but their role is unknown. Therefore, we examined the effect of host macrophage depletion on xenograft rejection. METHODS: Nonobese diabetic (NOD) mice were given clodronate-loaded liposomes intravenously to deplete macrophages. Controls received phosphate-buffered saline (PBS) or PBS-liposomes. General immune status was assessed after 2, 3, and 7 days by (1) fluorescence-activated cell sorter analysis of peripheral blood, spleen, and lymph node cells, (2) immunohistochemistry on spleens, and (3) mixed lymphocyte reaction. Organ-cultured fetal pig pancreas was transplanted under the kidney capsule of NOD mice 3 days after clodronate or PBS injection. Grafts were assessed histologically at 4, 5, 6, and 8 days after transplantation. RESULTS: Splenic macrophages and peripheral blood monocytes were depleted 2 days after clodronate treatment but had recovered within 11 days. T cell, B cell, and dendritic cell numbers were normal in spleen, peripheral blood, and lymph nodes of clodronate-treated mice, and T cells and antigen-presenting cells from these mice functioned normally in mixed lymphocyte reaction. Clodronate treatment markedly reduced graft infiltration by macrophages, T cells, and eosinophils at 4, 5, and 6 days after transplantation, and was associated with maintenance of endocrine cell viability and insulin expression. However, all grafts were rejected 8 days after transplantation, concordant with reappearance of splenic macrophages. CONCLUSIONS: Short-term, specific depletion of macrophages markedly delayed cellular infiltration and rejection of xenografts. The results provide the first evidence that macrophages promote T-cell infiltration and rejection of fetal pig pancreas xenografts in NOD mice.     

Roles of gastrin and somatostatin in the regulation of gastric acid secretion in the fetal rabbit

In adult gastric epithelium, gastrin and somatostatin regulate parietal cell acid secretion; however, their expression and function in the fetus are largely unknown. We defined the developmental expression of gastrin and somatostatin in the fetal rabbit stomach and determined their effects on fetal acid secretion. To define peptide expression, fetuses from 12 time-mated New Zealand white rabbit does were analyzed at successive ages during the third trimester (term is 31 days). Peptides were extracted from fetal gastric tissue by boiling in water and then in acetic acid. Amidated gastrin and somatostatin levels were measured by radioimmunoassay using antisera 1296 for gastrin and 8402 for somatostatin. To determine the effects of gastrin and somatostatin, pentagastrin (64 microg/kg/hr) or octreotide (35 microg/kg/hr) were infused intravenously in conscious pregnant rabbits at 28 days of gestation for 3 hr. Fetuses (n = 45) were harvested and gastric acid was titrated with 0.02 N NaOH. Gastrin and somatostatin tissue content were 12 +/- 3 and 51 +/- 6 pmol/g at gestational day 20, respectively, and increased to 146 +/- 10 and 162 +/- 5 pmole/g by day 30 (P < 0.05). Between days 24 and 26, when gastric acid was first detectable, the molar ratio of somatostatin to gastrin decreased from 5.0 +/- 1.0 to 1.1 +/- 0.1 (P < 0.05). Fetal gastric acid content (micromole) was 28.5 +/- 1.7 in controls, 27.5 +/- 1.9 with pentagastrin treatment, and 15.8 +/- 1.4 micromole with octreotide (P < 0.05). In summary, 1) In fetal gastric tissue, gastrin increased 12-fold and somatostatin increased 3-fold between days 20 and 30 of gestation. 2) The decreased ratio of somatostatin to gastrin between days 24 and 26 of gestation coincides with the onset of fetal gastric acid secretion in the fetal rabbit. 3) Maternal administration of octreotide inhibited fetal gastric acid content; however, pentagastrin had no effect. We conclude that, in the fetal rabbit stomach, the relative expression of gastrin and somatostatin may regulate the onset of parietal cell acid secretion.