Effect of Somatostatin on Normal and Gastric-Stimulated Cell Proliferation in the Gastric and Intestinal Mucosae of the Rat

Lehy, Thérèse; Dubrasquet, M; Bonfils, S

doi:10.1159/000198330

Cited by 99 publications

(40 citation statements)

References 18 publications

(24 reference statements)

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“…Injections of gastrin did not significantly affect cell proliferation of small intestinal epithelial cells, but stimulated cell proliferation in the colon of rats (Fatemi et al 1984). Somatostatin, on the other hand, had an inhibitory effect on DNA synthesis of gastrointestinal stem cells in vivo in rats (Lehy et al 1979) and rat intestinal epithelial cells in vitro (Bjork et al 1993). Somatostatin and its analogs have been shown to induce enterocyte apoptosis and impair intestinal regeneration after resection in rabbits (Thompson 1998.…”

Section: Physiological Mediators Of Intestinal Apoptosismentioning

confidence: 97%

Hormonal regulation of physiological cell turnover and apoptosis

Medh

Thompson

2000

Cell Tissue Res

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Physiological cell turnover plays an important role in maintaining normal tissue function and architecture. This is achieved by the dynamic balance of cellular regeneration and elimination, occurring periodically in tissues such as the uterus and mammary gland, or at constant rates in tissues such as the gastrointestinal tract and adipose tissue. Apoptosis has been identified as the prevalent mode of physiological cell loss in most tissues. Cell turnover is precisely regulated by the interplay of various endocrine and paracrine factors, which modulate tissue and cell-specific responses on proliferation and apoptosis, either directly, or by altering expression and function of key cell proliferative and/or death genes. Although recent studies have provided significant information on specific tissue systems, a clearly defined pathway that mediates cell turnover has not yet emerged for any tissue. Several similarities exist among the various tissues with regard to the intermediates that regulate tissue homeostasis, enabling a better understanding of the general mechanisms involved in the process. Here we review the mechanisms by which hormonal and cytokine factors mediate cell turnover in various tissues, emphasizing common themes and tissue-specific differences.

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Section: Physiological Mediators Of Intestinal Apoptosismentioning

confidence: 97%

Hormonal regulation of physiological cell turnover and apoptosis

Medh

Thompson

2000

Cell Tissue Res

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“…The native peptide is widely distributed in the body and, amongst its many inhibitory actions, has a putative role as an anti-proliferative agent in both normal (Lehy et al, 1979) and malignant tissue. The mechanisms involved in this anti-proliferative action have not, as yet, been confirmed.…”

mentioning

confidence: 99%

Somatostatin binding in normal and malignant human gastrointestinal mucosa

Miller

Farmery²,

Woodhouse³

et al. 1992

Br J Cancer

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Summary Somatostatin is a regulatory peptide implicated in the control of cellular proliferation in epithelial tissues and this regulation may occur directly via membrane bound receptor activation. The aim of this study was to investigate somatostatin binding in human gastrointestinal cancer and normal mucosa. Plasma membranes were prepared from specimens of tumour and normal mucosa from 51 patients undergoing surgical resection for malignancy (28 gastric, 23 (Horowitz et al., 1975;Higgins et al., 1941;Crile, 1957;Osei et al., 1985). There is, however, no currently defined role for endocrine therapy in non-endocrine gastrointestinal cancer. Surgical intervention is the most effective treatment for this condition and, even then, can only afford a 'cure' in early disease. Advanced tumours are associated with a poor prognosis, marginally improved by chemotherapeutic regimens. Any benefit from systemic therapy is usually abrogated by systemic toxicity (Rake et al., 1979;Engstrom et al., 1985;Bleiberg, 1990). For this reason a non-toxic, effective, treatment modality would be of value to improve the outlook for those patients with advanced disease.There is increasing evidence that tumours arising from the gastrointestinal tract are, at least in part, hormone dependent. Numerous hormones have now been implicated in the pathogenesis and development of gastrointestinal malignancy, including gastrin, epidermal growth factor, enteropancreatic hormones and oestrogenic steroids (Sirinek et al., 1985;Watson et al., 1988;Li et al., 1980;Howatson & Carter, 1985;McMichael et al., 1980). These findings, together with the observation that transformed gut epithelial cells may retain functional hormone receptors , have suggested a role for hormonal manipulation in these malignancies.Somatostatin and its analogues are good candidates for use as endocrine agents in the treatment of gastrointestinal cancer. The native peptide is widely distributed in the body and, amongst its many inhibitory actions, has a putative role as an anti-proliferative agent in both normal (Lehy et al., 1979) and malignant tissue. The mechanisms involved in this anti-proliferative action have not, as yet, been confirmed. Both the native peptide and its analogues act at the somatotrophs of the anterior pituitary suppressing growth hormone production and release (Adrian et al., 1981). This may influence the proliferation of target tissues directly or may result in a substantial reduction in local growth factor release (Kirkegaard et al., 1984 (Reubi et al., 1987a;Reubi et al., 1987b;Reubi et al., 1990;Ikuyama et al., 1985). Somatostatin (1981). In brief, frozen tumour and mucosal samples were mechanically pulverised and homogenised on ice in homogenising buffer (sucrose 250 mM, KCI 25 mM and MgCl2 10 mM in Tris-HCI 50 mM; pH 7.4) at 10,000 r.p.m. in short bursts for 2 min using an Ultraturrax T25 homogeniser (Scientific

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“…Later, a direct antiproliferative effect of octreotide on the gastric mucosa (as documented for somatostatin-14 in the rat (27)), as well as a diminished trophic effect of gastrin may become effective. This is in keeping with the reduction in the volume and density of endocrine cells (mostly ECL cells) in the body mucosa (by 43 and 21% respectively) found in hypergastrinemic patients after 6 months of octreotide therapy (37).…”

Section: Intragastric Aciditymentioning

confidence: 96%

“…We have previously demonstrated that this inhibition of gastrin secretion persists during long-term treatment (several years) in acromegalic patients (18). As gastrin is an important trophic factor in the gastric mucosa (27), long-term disturbance of its physiological secretion could adversely affect mucosal morphology.…”

Section: European Journal Of Endocrinology (1998) 139mentioning

confidence: 97%

“…We have shown previously that longterm (several years) octreotide treatment of acromegalic patients carries a risk of chronic active gastritis, although its incidence is a matter of discussion (14)(15)(16). Both a direct antiproliferative effect (27) of octreotide and inhibition of trophic factors (gastrin, histamine) (36,42) could weaken the physiological gastric mucosal regeneration. On the other hand, octreotide-induced GH inhibition may diminish the risk of gastrointestinal malignancy in acromegaly (19,20).…”

Section: Gastric Mucosal Histologymentioning

confidence: 99%

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