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)

The effect of a long-acting somatostatin analogue SMS 201-995 on GH secretion was investigated. Eleven acromegalic patients received a single dose of 50 micrograms SMS 201-995 administered subcutaneously, and plasma GH, IGF-I, GRF, TSH, IRI and blood glucose were determined at regular intervals. Nine of 11 patients had elevated basal plasma GH levels above 5 ng/ml. In all patients, plasma GH levels fell immediately from 39.5 +/- 17.3 ng/ml (mean +/- SEM) to 4.3 +/- 1.6 ng/ml (P less than 0.05) with a maximal inhibition of 82.9 +/- 3.3% of the basal levels and the suppression persisted for about 6 h of the observation period. IGF-I and GRF levels were not apparently altered. TSH and IRI levels also rapidly fell. Blood glucose levels fell slightly by 0.5 h. Ten of 11 patients had pain at injection sites. Except for this, no side effects were observed. Our results show that the new somatostatin analogue SMS 201-995 may inhibit GH hypersecretion in acromegalic patients for significant periods, suggesting that this agent can be a useful clinical tool for the treatment of acromegaly.
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PMID:Effect of a single administration of somatostatin analogue (SMS 201-995) on GH, TSH and insulin secretion in patients with acromegaly. 288 93

Corticotropin-releasing factor (CRF) and both human pancreatic growth hormone-releasing factor (hp-GRF) and rat hypothalamic GRF (rh-GRF) stimulated ACTH release from neoplastic AtT-20 mouse pituitary tumor cells in a dose-dependent fashion, with CRF inducing a 10-fold increase and GRF a maximal increment of approximately one-half that of CRF. Neither rh-GRF nor hp-GRF induced ACTH release in normal anterior pituitary cells. Pretreatment with either dexamethasone or somatostatin prior to the addition of rh-GRF inhibited the increase in ACTH release. Both ovine CRF and rh-GRF stimulated adenosine 3,5-monophosphate production in AtT-20 cells. The weak but clearly discernible effect of GRF on ACTH release from AtT-20 cells may be due to an abnormality in the AtT-20 cell receptor.
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PMID:Growth hormone-releasing factor releases ACTH from an AtT-20 mouse pituitary tumor cell line but not from normal pituitary cells. 288 43

We established in culture a clonal strain (44-2C) which produces calcitonin (CT), CT gene-related peptide, neurotensin (NT), and somatostatin (SS). A compendium of experimental data detailing for this strain the differential regulation of NT, CT, and SS synthesis and secretion, adenylate cyclase activation, and cAMP efflux is presented herein. The effects of hypophysiotropic peptides, brain-gut peptides, and catecholamines are described in detail. The effects of steroid hormones, and in particular, that of the synthetic glucocorticoid, dexamethasone, are presented. The effect(s) of basic bovine fibroblast growth factor are also described. In 44-2C cells basic fibroblast growth factor selectively regulates the synthesis and secretion of CT, NT, SS, and cAMP. Moreover, basic fibroblast growth factor enhances the responsiveness of 44-2C cells to neurosecretory peptides such as rat hypothalamic GRF. We conclude that the 44-2C cells are a useful in vitro tool to study the cellular mechanism(s) controlling the differential synthesis and secretion of neuropeptides.
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PMID:The neuropeptide-synthesizing rat 44-2C cell line: regulation of peptide synthesis, secretion, 3,'5'-cyclic adenosine monophosphate efflux, and adenylate cyclase activation. 288 76

We have earlier demonstrated that human growth hormone stimulates DNA synthesis and proteoglycan production in cultured chondrocytes. The present study is concerned with the effects of somatostatin and other neuropeptides on cell proliferation by cultured rat rib growth plate chondrocytes. Chondrocytes were isolated from the growth plates by collagenase digestion and cultured as monolayers in multiwell plates. The cells were allowed to attach overnight and subsequently incubated for 24 h under serum-free conditions to establish growth arrest. Somatostatin and other peptides were then added and the cultures were incubated for 18 h. Finally, the cultures were labelled for 6 h with tritiated thymidine in the presence of peptide. For screening purposes, the effect on DNA-synthesis was assayed as incorporation of [3H]-thymidine into acid-insoluble material. For a more exact estimate, parallel cultures were prepared for autoradiography and the fraction of labelled nuclei was determined by counting. Among the peptides we tested (somatostatin, GRF, TRH, SP, mENK, PHI, VIP, hCT) only somatostatin had any discernible effect on DNA synthesis, with an apparently optimal effect at 10 fM. This concentration is well within the range found in various tissues in vivo and suggests a physiological role for somatostatin in chondrocyte growth regulation. Further experiments are required, however, to clarify by which mechanism somatostatin influences the cells and whether the peptide interacts with other growth factors such as the IGFs.
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PMID:Stimulative effect of somatostatin on cell proliferation in cultured chondrocytes. 288 5

In order to determine whether there is an abnormality in the pituitary responsiveness to GRF in the diabetic rat, we examined the in vivo and in vitro effects of hGRF-44 NH2 (hGRF) on growth hormone (GH) release in the spontaneously diabetic BB Wistar rat. Under pentobarbital anesthesia, hGRF was injected intravenously at a dose of 500 ng/kg in male diabetic BB Wistar rats (n = 11) and in male control Wistar rats matched for weight (n = 11). Basal serum GH concentrations were significantly lower in the diabetic group, (123 +/- 5 ng/ml, mean +/- SEM) than in the control group (362 +/- 15 ng/ml). However, the GH response to hGRF was significantly greater in the diabetic group (GH increment 873 +/- 153 ng/ml) than in the control group (268 +/- 91 ng/ml). The effect of hGRF was further tested in a perifusion system of freshly dispersed anterior pituitary cells of diabetic BB Wistar rats and control Wistar rats. Basal secretion rate of GH from cells of diabetic rats (0.85 +/- 0.06 microgram/2 pituitaries X 2 min) was lower than that from cells of control rats (1.60 +/- 0.18 micrograms/2 pituitaries X 2 min). The GH response to 2-min pulses of hGRF at concentrations of 1.56, 6.25, and 25 pM with and without somatostatin 10(-9) M was significantly greater in the diabetic group than in the control group. In conclusion, there is in the spontaneously diabetic rat an increased in vivo and in vitro GH responsiveness to exogenous hGRF suggesting an abnormality of GH regulation at the pituitary level.
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PMID:Growth hormone responsiveness in vivo and in vitro to growth hormone releasing factor in the spontaneously diabetic BB Wistar rat. 288 37

We have examined the regulation of GH secretion from monolayer cultures of prepubertal male lamb anterior pituitary cells. Growth hormone-releasing factor (GRF 1-44) stimulated GH release in a dose-related manner: the maximal effective dose was 10(-10) M, which caused a 500% increase in basal GH secretion, while the half-maximal effect was reached with a dose of 2.5 x 10(-11) M (ED50). Thyrotropin-releasing hormone (TRH) also elicited a dose-dependent stimulation of GH secretion, although it was approximately 1000 times less potent than GRF. GRF and TRH did not have additive or synergistic effects on GH secretion. Somatostatin (SRIF) at a concentration of 10(-7) M maximally inhibited basal GH release to 40% of that of the control; the ED50 was 2.0 x 10(-9) M. Moreover, 10(-7) M SRIF blocked the stimulation of GH secretion induced by 10(-8) M GRF. However, when the cells were incubated with these two peptides at an identical concentration (10(-8) M), GH secretion was stimulated significantly above control values. When added at the same concentration (10(-7) M, TRH ans SRIF nullified their respective effects. A dose of 100 ng/ml of synthetic IGF-I was without effect on basal GH release, but significantly decreased 10(-9) M GRF-induced stimulation of GH secretion. these data indicate that in prepubertal male lambs: the stimulatory effect of GRF is predominant over the inhibitory effect of SRIF, somatostatin inhibits TRH stimulation of GH secretion in vitro, and IGF-I may control GH secretion by modulating GRF effects at the pituitary level.
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PMID:Effects of hypothalamic hormones (GRF, TRH, somatostatin) and insulin-like growth factor I on growth hormone secretion from prepubertal male lamb pituitary cultures. 288 68

The ability of human (h)GRF-(1-29)NH2 to stimulate GH secretion was studied in cannulated adult rats. In order to suppress endogenous GRF secretion and the inhibitory action of hypothalamic somatostatin (SRIF), rats were anesthetized with sodium pentobarbital. Intravenous administration of hGRF-(1-29)NH2 elicited a dose-dependent response of plasma GH, with 250 ng/kg being the smallest effective dose in male rats. In female rats, for each dose tested (250 to 70,000 ng/kg), the GH response represented only about 60% that of male rats. Repeated iv stimulations with hGRF-(1-29)NH2 at short time intervals (45 min) produced transient desensitization of pituitary responsiveness to GRF: a blunted GH response to the second and third stimulations was observed both in male and in female rats and for each dose tested. Similar blunted responses were also obtained with repeated injections of native hGRF-(1-44)NH2. The possibility that these blunted responses could be due to incomplete suppression of hypothalamic SRIF secretion by sodium pentobarbital was excluded by the use of rats that were passively immunized against SRIF; in these rats, it was shown that at least 65% of the inhibition of the GH response after the second GRF stimulation was unrelated to SRIF action. Similar transient desensitization to repeated hGRF-(1-29)NH2 stimulations was also observed in conscious rats that were passively immunized against SRIF. This occurrence of blunted responses was shown to be related to the length of the time interval between GRF stimulations, with longer intervals resulting in less or no desensitization. It appears thus that modulation of pituitary responsiveness to the action of GRF is mediated by at least two independent mechanisms in the rat: in addition to the inhibitory action imposed by hypothalamic SRIF, which induces periods of refractoriness to the action of GRF, it was shown in this study that in the pituitary level each GRF stimulation also induces a transient desensitization of somatotrophs for about 1 h. This period of refractoriness might not be due to excessive stimulation with GRF, since it was also observed with the lowest dose of hGRF-(1-29)NH2 that gave a significant release of GH. Finally, a sex difference was confirmed for the response of anesthetized adult rats to stimulation with hGRF-(1-29)NH2, reflecting a sex steroid-induced modification of pituitary responsiveness to GRF stimulation.
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PMID:Plasma growth hormone (GH) response to intravenous GH-releasing factor (GRF) in adult rats: evidence for transient pituitary desensitization after GRF stimulation. 288 46

Pharmacological characterization of somatostatin (SRIF) receptors located on somatotrophs, thyrotrophs, and lactotrophs was attempted by measuring the effects of 14 structural agonists of somatostatin (SRIF) on the inhibition of basal and GRF-stimulated GH and basal and TRH-stimulated PRL and TSH secretion. We also checked the abilities of the analogs to displace [125I]N-Tyr-SRIF binding to pituitary cell membranes and their potency to inhibit adenylate cyclase activity. There was a very good correlation (r = 0.975) between the displacement of [125I]N-Tyr-SRIF and the inhibition of adenylate cyclase activity by the analogs. The effects of the analogs on secretion of the three hormones followed the same rank order of potency. However, the active analogs displayed 2-6 times lower affinities in inhibiting PRL than GH or TSH secretions. The shift in affinity was even more pronounced in the case of the lower potency of the analogs as inhibitors of adenylate cyclase activity compared to hormone secretions. Pretreatment of the cells with pertussis toxin (100 ng/ml; 24 h) blocked SRIF inhibition of basal and GRF-stimulated adenylate cyclase activity and decreased by 83% [125I]N-Tyr-SRIF binding. It also blocked the ability of SRIF to inhibit GRF-induced GH and TRH-induced PRL and TSH secretion. However, pertussis toxin also increased GRF stimulation of GH secretion and decreased TRH stimulation of both TSH and PRL secretion. We conclude from our data that SRIF-binding sites located on the three target cells of the adenohypophysis are of a single class. These binding sites are negatively coupled to adenylate cyclase, but the inhibition of hormone secretions by SRIF cannot be explained solely through adenylate cyclase inhibition. Another mechanism of transduction must be involved in the actions of SRIF on its three pituitary target cells.
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PMID:Somatostatin receptors on pituitary somatotrophs, thyrotrophs, and lactotrophs: pharmacological evidence for loose coupling to adenylate cyclase. 289 May 15

In vivo and in vitro studies of beta-adrenergic influences on GH secretion have produced apparently conflicting data in which the in vivo effect seems to be inhibitory and the in vitro effect to be stimulatory. The present studies were designed to observe the in vivo effect of isoproterenol (ISO), a beta-adrenergic agonist, on 1) GH release during a brief interval after intraatrial infusion, and 2) GH release in response to GRF infused 10 min after ISO. ISO was found to stimulate GH release in both intact and hypothalamus-lesioned animals within 2 min after infusion, but GH returned to control levels within 10 min. ISO also profoundly inhibited the release of GH in response to GRF. Pretreatment of animals with somatostatin (SRIF) antiserum prevented the inhibitory action of ISO on GRF-induced GH release. No change in peripheral levels of SRIF was detected. Also, there was no suppression of GRF-induced GH release by ISO when the treatments were applied in vitro to dispersed perifused pituitary cells. These data show that beta-adrenergic systems can stimulate a rapid but brief release of GH in vivo, and that the subsequent inhibitory action on GRF-induced GH release might be by means of SRIF release.
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PMID:Beta-adrenergic stimulation of growth hormone (GH) release in vivo, and subsequent inhibition of GH-releasing factor-induced GH secretion. 289 64

The multipeptide-secreting 44-2C cell line maintains differentiated function when grown in a serum-free, growth factor- and hormone-deprived milieu. The cells continue to synthesize and secrete calcitonin (CT), CT gene-related peptide, neurotensin, and somatostatin and respond to cellular secretagogues such as GRF and acidic and basic fibroblast growth factor. We designed experiments to ascertain the functional role(s) of cellular factors involved in the maintenance of the differentiated state in 44-2C cells. We report here the phenotypic transformation that occurs in these cells in the course of adjustment to the serum-free state. We also show the differential increase in CT-specific mRNA, the transient induction of c-fos, and the characterization of biologically active acidic fibroblast growth factor.
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PMID:Induction of c-fos, calcitonin gene expression, and acidic fibroblast growth factor production in a multipeptide-secreting neuroendocrine cell line. 289 27


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