Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermal growth factor (EGF), phorbol esters (PEs), and retinoic acid (RA) inhibit differentiated functions of thyrocytes. In the present study the inhibitory effects of these growth-promoting factors on hormone synthesis were studied in thyroid follicles cultured in type-I collagen gel, and morphologic alteration by these factors was examined by light and electron microscopy (EM). Porcine open thyroid follicles obtained by treatment with 0.1% collagenase were embedded in collagen gel and cultured in Ham's F12 medium supplemented with 6H (insulin, hydrocortisone, somatostatin, transferrin, glycyl-his-lys, and thyrotropin) + 0.5% fetal bovine serum (FBS). After 1 week these open follicles developed to closed follicles, and the medium was changed to one containing 6H + 0.5% FBS + 0.1 microM sodium iodide (NaI). Some media were supplemented with either EGF, phorbol 12-myristate 13-acetate (PMA), or all-trans RA. The closed follicles retained ability for hormone synthesis for 2 weeks after the medium change in the presence of 6H + FBS + NaI. The amounts of T4 and T3 secreted into the culture medium from day 9 to day 12 after the medium change were 60% and 45% of those from day 0 to day 4, respectively. EGF reduced production of T4 and T3 by 61% and 69%, respectively; PMA, by 87% and 99%; and RA, by 55% and 44%. In the medium supplemented with 6H + 0.5% FBS, the follicles exhibited intact polarity. Apical surfaces with microvilli were oriented to the follicular lumen and tight junctions were on the apical side of cell-to-cell contacts. Desmosomes were found on both the apical and basal halves of the cell contacts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of epidermal growth factor, phorbol ester, and retinoic acid on hormone synthesis and morphology in porcine thyroid follicles cultured in collagen gel. 149 78

Duodenal biopsies obtained from seven normal subjects and six ulcerous patients were cultured in vitro for 30 min at 37 degrees C under various experimental conditions. Epidermal growth factor (EGF) and somatostatin released in the culture medium were determined by radioimmunoassay. Under basal conditions, EGF and somatostatin levels were significantly higher in normal subjects (11.49 +/- 3.07 ng/mg protein and 3.06 +/- 0.8 ng/mg protein, respectively) than in ulcerous patients (6.9 +/- 1.98 ng/mg protein and 1.75 +/- 1.23 ng/mg protein, respectively). However, when antibodies to somatostatin and vasoactive intestinal polypeptide (VIP) were added together to the culture media, in ulcerous patients, EGF levels also were lower as absolute values, but were higher as a percentage of variation than controls (p less than 0.05). The fall of EGF secretion from tissue cultures of ulcerous patients could be the consequence of endocrine cellular loss or damage, rather than the cause of ulceration. Moreover, the EGF-producing cells around the lesion in ulcerous patients seems to be hyperactive, and this hyperfunction of EGF-producing cells might contribute to the in vivo repair of tissue damage.
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PMID:The role of epidermal growth factor in the pathogenesis of peptic ulcer disease. 167 87

Several studies have reported effects of gastrointestinal regulatory peptides on growth of experimentally induced pancreatic neoplasms and human cancer cell lines. The growth of human pancreatic cancer lines PANC-1 and MIA PaCa-2 was characterized in vitro, and the effects of cholecystokinin, bombesin, insulin, epidermal growth factor, secretin, vasoactive intestinal peptide, and somatostatin were determined. Fetal bovine serum was required for initiation of growth in both cell lines. Growth effects of peptides were determined by incubating cells with peptides in serum-free medium after a 72-h preincubation in 10% serum-supplemented medium alone. Epidermal growth factor (3.4 x 10(-9) M) and insulin (10(-6) M) significantly (p less than 0.001) increased growth of both cell lines as determined by increases in deoxyribonucleic acid and protein. Bombesin, secretin, vasoactive intestinal peptide, and somatostatin (all 10(-8) M) did not affect growth of either cell line. Neither cholecystokinin-8 nor [Thr4, Nle7] cholecystokinin-9 altered growth in concentrations from 10(-12)-10(-6) M. Anchorage-dependent clonogenic growth of both cell lines was also not altered by cholecystokinin-8. Cholecystokinin added to cultures was degraded by separate effects of serum and cells. Addition of cholecystokinin-8 to cultures every 8 h maintained cholecystokinin levels but did not alter cell growth. These data support roles for epidermal growth factor and insulin as growth factors for human pancreatic cancer cell lines.
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PMID:Growth effects of regulatory peptides on human pancreatic cancer lines PANC-1 and MIA PaCa-2. 218 57

The regulation of gastrin gene transcription was studied in GH4 pituitary cells transfected with constructs comprised of the first exon of the human gastrin gene and various lengths of 5' regulatory sequences ligated upstream of the reporter gene chloramphenicol acetyltransferase. Gastrin reporter gene activity in GH4 cells was equal to the activity of a reporter gene transcribed from the endogenously expressed growth hormone promoter. The effect of a variety of peptides on gastrin gene transcription including epidermal growth factor (normally present in the gastric lumen), gastrin-releasing peptide, vasoactive intestinal peptide, and somatostatin (present in gastric nerves) was assessed. Epidermal growth factor increased the rate of gastrin transcription almost 3-fold, whereas thyrotropin-releasing hormone and vasoactive intestinal peptide increased gastrin transcription 2- and 1.5-fold, respectively. Gastrin-releasing peptide, a peptide that strongly stimulates gastrin release, weakly increased gastrin transcription (1.3-fold). Somatostatin inhibited the increase in gastrin transcription induced by epidermal growth factor, thyrotropin-releasing hormone, and vasoactive intestinal peptide. Constructs containing various lengths of 5' regulatory sequences defined a response element -40 to -82 base pairs (bp) 5' to the transcription initiation site. This 40-bp sequence contains Sp1 and AP2 binding sites, which suggests that epidermal growth factor and thyrotropin-releasing hormone stimulate gastrin gene transcription through transcription factors that bind to Sp1 and/or AP2 motifs.
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PMID:Regulation of the gastrin promoter by epidermal growth factor and neuropeptides. 256 64

Epidermal growth factor (EGF) is localised in man to salivary and Brunner's glands. It is present in large concentrations in saliva and duodenal contents but the mechanisms of its release have been little studied. This study carried out on four groups of healthy subjects was designed to determine the distribution and the release of immunoreactive EGF (IR-EGF) in salivary, gastric, duodenal, and pancreatic secretions. Under basal conditions, the concentrations of IR-EGF in salivary, gastric, duodenal and pancreatic secretions were; 2.7 (0.4), 0.42 (0.12), 21 (5) and 8.5 (1.2) ng/ml, respectively. Chewing of Parafilm* significantly increased salivary but not gastric or duodenal EGF output while atropinisation led to the reduction in basal salivary and duodenal EGF output without affecting the increment in EGF release induced by chewing. Cigarette smoking caused a marked reduction in basal salivary and duodenal EGF output. Infusion of pentagastrin increased salivary and duodenal EGF output and this was blocked by the addition of somatostatin. Injection of secretin lead to an increase in pancreatic output of EGF. We conclude that in man the major sources of EGF are salivary glands, duodenum, and pancreas and that the release of EGF remains under neurohormonal control.
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PMID:Distribution and release of epidermal growth factor in man. 280 86

Epidermal growth factor (EGF) stimulates the growth of many tissues and inhibits stimulated gastric acid secretion. Its primary tissue of origin in man is still unknown. We used polyclonal anti-human EGF sera in the peroxidase-antiperoxidase immunocytochemical staining technique to identify immunoreactive human EGF (ihEGF) in tissue sections from 29 subjects ranging from fetuses to 63 years in age. In addition to acinar cells in the submandibular salivary glands and cells of Brunner's duodenal glands, previously reported to contain ihEGF, we found ihEGF in most anterior pituitary glycopeptide hormone-secreting cells, in gastric and pyloric gland cells of the stomach, and in bone marrow cells that resembled mononuclear phagocytes in subjects of all ages. The eccrine sweat glands in the skin of adults also contained ihEGF. Cells containing ihEGF were found singly or in clusters in the trachea of the fetus only. No fetal pancreatic islet cells stained, but occasional cells in neonates and a majority of islet cells in older subjects contained ihEGF; there was no constant association with insulin, glucagon, or somatostatin. Only the lactating breast contained ihEGF. In adults, outer adrenomedullary cells contained ihEGF. Intense immunostaining was observed in the renal medulla, apparently limited to the extracellular area between the renal tubules, and increased with age; the cortex was devoid of ihEGF. No ihEGF was detected in posterior pituitary gland, thyroid gland, heart, lung, or liver at any age. An adult prostate contained ihEGF only in an area of local injury, and some primordial follicles from the ovary of a newborn appeared to contain ihEGF. Thus, many tissues appear to synthesize hEGF, which may exert exocrine, endocrine, or paracrine functions in different tissues and at different ages.
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PMID:Immunocytochemical localization of human epidermal growth factor/urogastrone in several human tissues. 388 5

A non-transformed small-intestinal cell line from the rat (IEC-6) and a human colon cancer cell line (HT 29) were examined for their trophic response to sensory neuropeptides. Substance P, neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and peptide YY (PYY) were tested. Epidermal growth factor (EGF), insulin, and somatostatin-14 were also used. Interaction studies were performed on IEC-6 cells by combining EGF or insulin with somatostatin-14. The sensory neuropeptides had no effect either on IEC-6 cell growth and DNA synthesis or on HT29 cell growth. EGF and insulin stimulated cell growth and DNA synthesis in IEC-6 cells and cell growth in HT 29 cells in a dose-dependent fashion. Somatostatin-14 had no effect either alone or in combination with EGF or insulin on IEC-6 cell growth and DNA synthesis. HT 29 cell growth was inhibited by somatostatin-14 only in the presence of serum with a maximal and significant response at 10(-7) M. Our observations suggest that the sensory neuropeptides do not exert a direct growth-regulatory effect either on IEC-6 cells or on HT 29 cells. Somatostatin, however, inhibits serum-induced HT 29 cell growth but does not interfere directly with the proliferative effect of serum, EGF, or insulin on IEC-6 cells in this model.
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PMID:Growth-regulatory effects of sensory neuropeptides, epidermal growth factor, insulin, and somatostatin on the non-transformed intestinal epithelial cell line IEC-6 and the colon cancer cell line HT 29. 750 79

There is now clear-cut evidence that polypeptide growth factors control the proliferation of the normal gastrointestinal mucosa. Epidermal growth factor (EGF) stimulates normal growth throughout the gastrointestinal tract, and accelerates the healing of ulcerated epithelium. While the effects of gastrin were at first thought to be similarly widespread, the gastrin target now appears to be restricted to the enterochromaffin-like cells in the stomach. Isolated reports suggest that several other hormones, including fibroblast growth factor and the insulin-like growth factors, have similar proliferative effects. In contrast, indirect evidence suggests that somatostatin and transforming growth factor-beta inhibit the growth of the gastrointestinal mucosa. The same growth factors profoundly affect the growth of some gastrointestinal carcinomas. Prolonged hypergastrinaemia increases the risk of development of gastric endocrine tumours, but has no effect on the incidence of gastric adenocarcinoma. Gastrin also stimulates the in vivo growth of 50% of gastric and colorectal carcinoma xenografts, but has no consistent effect on the growth of carcinoma cell lines in vitro. EGF, on the other hand, significantly stimulates proliferation of many gastrointestinal cell lines in culture. Interest has recently focused on autocrine stimulation of gastrointestinal carcinoma growth. Elevated levels of EGF receptor, and of EGF or related mRNAs, have been demonstrated in gastric carcinomas, and the growth of some gastrointestinal cell lines is inhibited by antibodies against EGF, and by antisense oligonucleotides based on EGF mRNA. Similarly gastrin/cholecystokinin antagonists inhibit the growth of several colon carcinoma cell lines, although the spectrum of antagonist potencies suggests that classical gastrin and cholecystokinin receptors are not necessarily involved. Continued research on antagonists may therefore lead to novel therapies for gastrointestinal cancers.
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PMID:Gut hormones, growth and malignancy. 790 61

Interactions between growth factor receptor systems may be important in the regulation of cell growth. The proliferation of pancreatic tumor AR42J cells has been shown to be stimulated by Epidermal growth factor (EGF) and gastrin and inhibited by somatostatin. To analyze the interaction between these different peptides, we explored the influence of EGF and gastrin on the somatostatin receptors. Treatment of AR42J cells with 10 nM EGF or gastrin for 24 hr increased specific binding of [125I] Tyr3SMS to 131 and 147% of that in control cells, respectively. The effect of peptides on [125I]Tyr3SMS binding was time- and dose-dependent, with half-maximal effect at 0.2 +/- 0.03 nM EGF and 0.3 +/- 0.15 nM gastrin. Scatchard plots revealed an increase in somatostatin receptor number of 27 and 80% after 48 hr of treatment with EGF and gastrin, respectively, without any change in receptor affinity. The increase in somatostatin receptor density was accompanied by the enhancement of biological responses to somatostatin. In cells pretreated with EGF or gastrin, the potency of somatostatin for inhibiting vasoactive intestinal peptide-stimulated cAMP content was increased 2-fold as that of somatostatin analog, SMS, for inhibiting cell proliferation. Furthermore, the efficiency of SMS as antiproliferative agent was greatly increased. Vasoactive intestinal peptide or forskolin did not modify [125I]Tyr3SMS binding of control or treated cells. The phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) did not affect [125I]Tyr3SMS binding. On the other hand, cycloheximide completely blocked the increase in [125I]Tyr3SMS binding induced by EGF and gastrin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Up-regulation of somatostatin receptors by epidermal growth factor and gastrin in pancreatic cancer cells. 805 63

We reported previously that somatostatin inhibits the expression of the immediate early gene c-fos. Accordingly, we characterized the molecular mechanisms by which somatostatin inhibits c-fos gene expression. Because growth factors activate c-fos through a region of its promoter known as the serum response element [SRE; base pairs (bp) -357 to -276] we transfected rat pituitary adenoma cells (GH3) with plasmids containing the SRE or the SRE core fragment (bp -320 to -298) upstream of the luciferase reporter gene. Epidermal growth factor (EGF) stimulated SRE-luciferase activity, and this effect was inhibited by somatostatin and by the analog MK-678. Identical results were obtained with the SRE core plasmid, demonstrating that the sequence between bp -320 and -298 of the c-fos promoter is a somatostatin response element. Because the extracellular signal-regulated protein kinases (ERKs) induce the SRE via phosphorylation of transcription factors such as Elk-1, we examined the effect of somatostatin on ERK phosphorylation and activation. EGF stimulated tyrosine phosphorylation of ERK2, and MK-678 attenuated this effect. In experiments using in-gel kinase assays, MK-678 also inhibited EGF-stimulated ERK activity via a pertussis toxin sensitive pathway, and this effect resulted in inhibition of Elk-1 transcriptional activity. Our data suggest that one mechanism of somatostatin action involves inhibition of ERK activity, Elk-1 phosphorylation and transcriptional activation, and ultimately c-fos gene transcription.
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PMID:Molecular mechanisms for somatostatin inhibition of c-fos gene expression. 914 1


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