gastrin-releasing-peptide and Hyperplasia

Human pulmonary neuroendocrine cells produce a variety of hormones, including mammalian bombesin (BN) or gastrin-releasing peptide (GRP). Neuroendocrine cell hyperplasia and increased release of BN-like peptides occur in several diseases of the airways, including chronic obstructive pulmonary disease (COPD) and bronchopulmonary dysplasia. Growth stimulation of human bronchial epithelial cells by BN, as measured in a colony-forming assay, has been reported previously (Willey et al.:Exp. Cell Res. 153:245-248, 1984). In a follow-up to this report, we examined the response of human bronchial epithelial (HBE) cells to BN or GRP in a similar system, using cells derived from 13 human tissue donors. A stimulatory response (increased colony-forming efficiency) was found in cultures from 8 donors, including 3 with COPD. Statistical significance was found for the data from 5 of these 8 donors. The other 5 donors, 1 normal and 4 lung cancer patients, showed inhibition of colony formation by BN or GRP. Statistical significance was found for 3 of these donors. The ability of BN analogs to modulate BN stimulation was examined in cells from a donor with COPD. [psi Leu13,Leu14] BN(1-14), a BN antagonist, blocked the stimulation induced by BN. [D-Cpa6,psi Leu13,Phe14] BN(6-14), a mixed agonist-antagonist, showed partial agonist activity in HBE cells. [D-Phe1,Leu8,9] Litorin, an agonist, also showed agonist activity in a colony-forming assay with cells from these donors. These results indicate that responsiveness to BN/GRP may vary widely in the human population. Responsiveness may be heightened in disease states involving a proliferation of neuroendocrine cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bombesin; Bronchi; Cell Division; Epithelial Cells; Epithelium; Gastrin-Releasing Peptide; Humans; Hyperplasia; Lung Diseases, Obstructive; Lung Neoplasms; Peptides

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Cell Division; Cricetinae; Diethylnitrosamine; Gastrin-Releasing Peptide; Hyperplasia; Lung; Lung Neoplasms; Neurosecretory Systems; Peptides; Serotonin

We have found vasoactive intestinal polypeptide (VIP)-, neurotensin-, substance P-, gastrin-releasing peptide-, calcitonin-, calcitonin gene related peptide (CGRP-2)-, and somatostatin-like immunoreactivities in extracts of sporadic human parathyroid adenomas (n = 18). The content of CGRP-2, substance P, and somatostatin in adenomas correlated directly with that of parathyroid hormone. In addition, concentrations of VIP versus substance P and somatostatin versus CGRP-2 in adenomas were directly correlated. Neuropeptide content of parathyroid hyperplasias differed from that of adenomas. VIP was detected in only one of seven parathyroid hyperplasias, and neurotensin was undetectable (0/7), whereas substance P was present in six of seven cases and GRP in five of seven hyperplasias. In hyperplasias, content of substance P correlated directly with that of gastrin-releasing peptide. Peroxidase immunohistochemistry localized VIP-like immunoreactivity to 20% to 50% of both chief and oxyphilic cells and rare clear cells and capillary endothelium in 11 of 12 adenomas studied. Focal staining was present in glandular epithelium of the rim of adjacent normal parathyroid tissue and in two of three normal parathyroid glands removed with thyroid goiters. This staining was both cytoplasmic and apical membrane. By contrast, in adenomas, neurotensin- and substance P-like positivities were confined to scattered (5% to 10%) oxyphilic cells. Cytoplasmic positivity for parathyroid hormone, noted in 30% to 70% of cells in serial sections, confirmed that these tissues were indeed parathyroid glands.

Topics: Adenoma; Calcitonin; Calcitonin Gene-Related Peptide; Gastrin-Releasing Peptide; Humans; Hyperplasia; Immunoenzyme Techniques; Neuropeptides; Neurotensin; Parathyroid Glands; Parathyroid Neoplasms; Peptides; Radioimmunoassay; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Gastrin-releasing peptide immunoreactivity has been seen in functioning endocrine tumours which are recognized as a major cause of secretory diarrhea. The authors describe a case of a 52-year-old woman who had secretory diarrhea (5 L/d) with markedly elevated gastrin-releasing peptide levels associated with islet cell hyperplasia. No tumour could be identified. The diarrhea was controlled by somatostatin analogue.

Topics: Diarrhea; Female; Gastrin-Releasing Peptide; Humans; Hyperplasia; Injections, Subcutaneous; Islets of Langerhans; Middle Aged; Peptide Biosynthesis; Peptides; Somatostatin

Gastrin-releasing peptide (GRP), the mammalian homolog of bombesin, is often studied as a prototypic neuroregulatory hormone and growth factor, but its own regulation and physiological roles remain to be fully defined. We now demonstrate that the GRP gene is expressed in human thyroidal calcitonin (CT)-containing neuroendocrine cells (C-cells) in an ontogenic pattern similar to its expression in pulmonary neuroendocrine cells and is also expressed at high levels in C-cell hyperplasias and neoplasias (medullary carcinomas of the thyroid). Mean GRP-like immunoreactivity is 20 times higher in 3-week-old to 5-month-old infants than in normal adults, with six of seven infants having GRP levels 6- to 67-fold higher than those in normal adults, the highest levels occurring at 2-2.5 months. CT levels are about 100 times greater than GRP levels at all time intervals, with levels of GRP and CT being linearly correlated (r = 0.98). By RNA blot analysis, GRP mRNAs are increased in neonatal thyroids compared to adult thyroids. In situ hybridization and immunoperoxidase analyses localize GRP mRNAs and peptide to a majority of C-cells in fetuses and neonates, but to only 5-18% of C-cells in normal adults. The majority of developing C-cells have a dendritic morphology, suggesting a paracrine role, although this morphology is not observed in adult C-cells. In addition, for unknown reasons, an increased percentage of C-cells positive for GRP occurs in normal thyroid adjacent to GRP-negative follicular adenomas and papillary carcinomas, an association that we term perineoplastic. We hypothesize that GRP gene expression may play a role in both normal and neoplastic growth processes.

Topics: Adenoma; Adult; Bombesin; Carcinoma, Papillary; Gastrin-Releasing Peptide; Gene Expression Regulation; Humans; Hyperplasia; Immunohistochemistry; Infant, Newborn; Nucleic Acid Hybridization; Peptides; Radioimmunoassay; RNA, Messenger; Thyroid Gland; Thyroid Neoplasms