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)

Interleukin-1 (IL-1) receptors with kinetics, pharmacological and biochemical characteristics of type I IL-1 receptors have been identified in the mouse neuro-endocrine-immune axis. In the present study, we examined the in-vitro and in-vivo modulation of IL-1 receptors by stress and endotoxin treatment. The treatment of AtT-20 mouse pituitary adenoma cells for 24 hr with neuro-endocrine mediators of stress such as corticotropin releasing factor (CRF) and catecholamine (beta 2 adrenergic) receptor agonists produced a dose-dependent increase in cAMP and [125I]IL-1 alpha binding. In contrast, somatostatin and dexamethasone significantly inhibited CRF-stimulated cAMP production and decreased both basal and CRF-mediated increase of [125I]IL-1 alpha binding. Furthermore, in keeping with the effects of stress mediators to upregulate IL-1 receptors in AtT-20 cells, ether-laparotomy stress in mice resulted in a significant increase in [125I]IL-1 alpha binding in the pituitary with no significant alterations observed in the brain; in contrast, [125I]oCRF binding in the pituitary was significantly decreased after the ether-laparotomy stress. Next, we investigated the modulation of IL-1 beta levels and [125I]IL-1 alpha binding following endotoxin lipopolysaccharide (LPS) treatment. IL-1 beta levels were dramatically increased in the peripheral tissues (pituitary, testis and spleen) at 2-6 hr after a single LPS injection (30 micrograms LPS/mouse). However, no significant changes were observed in brain (hippocampus and hypothalamus). [125I]IL-1 alpha binding in the pituitary gland, liver, spleen and testis was significantly decreased at 2 hr following a single administration of both low (30 micrograms LPS/mouse) and high (300 micrograms LPS/mouse) doses of endotoxin. [125I]IL-1 alpha binding in the hippocampus was not significantly altered at 2 hr by a low dose of LPS and was significantly decreased by high dose administration of LPS (300 micrograms/mouse). Following two LPS injections (at 0 and 12 hr), dramatic increases in IL-1 beta concentrations in the hypothalamus, hippocampus, spleen and testis were observed at 2 hr after the second LPS injection; a small but statistically nonsignificant change was evident in the pituitary. Moreover, dramatic decreases in [125I]IL-1 alpha binding were seen after two injections of 30 micrograms LPS/mouse in both central and peripheral tissues. These data provide further support for a role for IL-1 in co-ordinating neuro-endocrine-immune responses to stress and infection.
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PMID:Modulation of interleukin-1 receptors in the neuro-endocrine-immune axis. 757 73

We have reported previously that the widespread inhibitory actions of somatostatin might be mediated by its ability to inhibit the expression of the immediate early genes c-fos and c-jun. The products of these genes form a heterodimeric transcription factor complex [activator protein 1 (AP-1)], which is known to be induced by treatment with phorbol esters. In the present study, we sought to investigate the mechanisms by which somatostatin inhibits immediate early gene expression. For our experiments, we used a rat pituitary adenoma cell line (GH3), which is known to express multiple subclasses of somatostatin receptors. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated both AP-1 binding and transcriptional activity in GH3 cells and the somatostatin analogue octreotide inhibited this response by 40-70%. In the presence of two different phosphatase inhibitors, sodium orthovanadate or okadaic acid, the ability of somatostatin to inhibit AP-1 binding and transcriptional activity was abolished. This effect of octreotide, which appears to be mediated by the SSTR2 and SSTR5 subtypes of somatostatin receptors, was paralleled by its ability to inhibit TPA-stimulated GH3 cell proliferation. Pretreatment of the GH3 cells with pertussis toxin (200 ng/ml) reversed the inhibitory effect of octreotide on both AP-1 function and cellular proliferation. Our observations lead us to conclude that somatostatin not only inhibits immediate early gene expression but also inhibits AP-1 binding and transcriptional activity via the action of several classes of protein phosphatases. This effect, which is pertussis toxin sensitive, might be one mechanism by which somatostatin inhibits cellular proliferation.
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PMID:Somatostatin inhibits AP-1 function via multiple protein phosphatases. 763 95

Somatostatin (SRIF) exerts its diverse biological effects through a family of membrane receptors. In addition to inhibiting GH secretion, SRIF has antiproliferative effects and has been used clinically in the treatment of pituitary tumors. SRIF receptor (SSTR) expression has recently been identified in pituitary adenomas, and it is unknown whether differential expression of SSTR subtypes predicts clinical responses to SRIF analogs. We therefore determined which SSTR subtype messenger RNAs (mRNAs) are expressed in pituitary adenoma phenotypes and in normal human pituitary tissue using reverse transcriptase-polymerase chain reaction and tested whether expression of specific SSTR subtype mRNA is necessary for SRIF inhibition of GH secretion in human somatotroph adenomas in vitro. Expression of SSTR subtypes 1, 2, and 5 mRNA was identified in all pituitary adenoma types and normal pituitary tissue. In contrast, SSTR3 mRNA was detected in only one somatotroph adenoma as well as in control insulinoma tissue, a tissue known to express SSTR3 mRNA, and was not detected in normal pituitary tissue. SSTR4 mRNA was not detected in any human pituitary tissue. To determine whether specific SSTR subtype mRNA expression is required for SRIF inhibition of GH secretion, five somatotroph adenomas were treated with 10(-7) mol/L SRIF in vitro, and significant inhibition of GH release occurred in all adenomas. All five tumors expressed SSTR2 mRNA and SSTR5 mRNA, and three expressed SSTR1 mRNA. The absence of SSTR1 mRNA expression did not affect the ability of SRIF to suppress GH secretion. We conclude that: 1) human pituitary adenomas and normal pituitary express multiple SSTR gene transcripts; 2) SSTR5 mRNA, which has not been reported in other human endocrine tumor types, is expressed in neoplastic and normal pituitary tissue; and 3) SSTR2 mRNA, SSTR5 mRNA, and variable SSTR1 mRNA are expressed in GH-secreting tumors, which are responsive to SRIF in vitro. Further understanding of SSTR gene expression in pituitary adenomas will facilitate our understanding of the pathogenetic mechanisms of tumorigenesis and may provide a rationale for the use of specific SRIF analogs for clinical application.
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PMID:Somatostatin receptor subtype gene expression in pituitary adenomas. 771 15

Non-functioning pituitary adenoma is a lesion usually large enough to produce loss of vision and often loss of libido. Transsphenoidal microsurgery is the treatment of choice of these patients. Postoperative radiation therapy should be performed in patients with significant residual pituitary adenoma. Some studies have recently reported that somatostatin analogue may be useful as adjuvant medical therapy, at least in order to improve visual field defects.
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PMID:[Treatment of the non-functioning hypophyseal adenoma]. 790 85

A 40-year-old male patient with a 2 years history of recurring hyperthyroidism is presented with clinical hyperthyroidism and diffuse goiter. Despite thyreostatic treatment and surgical thyroid ablation the hyperthyroidism recurred. The patient had laboratory evidence of hyperthyroidism and his serum TSH was persistently and enormously elevated (T4:214 nmol/l, T3:6.9 nmol/l, TSH:218 mIU/l)> Computed tomography and magnetic resonance imaging confirmed a pituitary mass of 7 cm in a-p diameter, with supra-, parasellar and sphenoidal extension. The pituitary adenoma was partially resected by transsphenoidal surgery, which failed to result in a substantial decrease in the serum thyrotropin level. Pituitary irradiation and a long-term somatostatin analog octreotide treatment (300-600 micrograms/die) combined with bromocriptine therapy resulted in a significant, but still incomplete suppression of thyrotropin secretion (TSH level about 15 mIU/l) and persisting mild hyperthyroidism. The size of the adenoma was unchanged during the two years of highdose octreotide treatment period. According to our best knowledge this is the first reported case of a thyrotropin-secreting pituitary adenoma in Hungary.
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PMID:[Thyroid-stimulating hormone-secreting pituitary adenoma]. 799 Dec 45

Octreotide is a synthetic octapeptide somatostatin analogue which has higher potency and longer duration of action than the natural hormone. It is effective after subcutaneous administration and no rebound hypersecretion has been observed. Pharmacological effects of octreotide include inhibition of numerous hormones (growth hormone, TSH, insulin, glucagon and all gut hormones), of exocrine secretion (gastric acid, pancreatic enzyme), and of small-bowel absorption. This review deals with clinical application of octreotide in endocrine disorder. In patients with acromegaly octreotide treatment results in decrease of growth hormone (GH) and IGF-I together with tumour shrinkage and clinical improvement. Although variability in response to treatment is obvious for majority of patients the most effective dose is 100 mcg three times daily subcutaneously. Normalization of GH levels could be achieved in more than 50% of treated patients. It has also been shown that octreotide could be effective in TSH secreting pituitary adenoma, ACTH secreting adenoma as well as in non-secretory pituitary tumours. A marked biochemical and clinical responses together with longer survival have been reported in most of the patients with gastroenteropancreatic (GEP) tumours. Patients who benefit the most from octreotide therapy are those with carcionid syndrome (successful control of diarrhoea, flushing episodes and wheezing) and VIPomas (control of diarrhoea). In patients with insulin-dependent diabetes mellitus (IDDM) octreotide suppresses GH levels, postprandial blood glucose increases with resultant decrease in daily insulin requirements. In women with polycystic ovary syndrome (PCOS) octreotide has inhibitory effect on serum LH and ovarian androgens. This could have beneficial effect on ovulatory performance in women with PCOS.
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PMID:[Clinical use of octreotide (Sandostatin) in endocrinology]. 799 11

We present a 55-year-old female with a thyrotropin (TSH)-secreting pituitary adenoma who had been treated with somatostatin analog octreotide acetate (SMS 201-995) for 4 months. Subcutaneous injection of 100 micrograms octreotide acetate twice daily resulted in significant reduction of the TSH, thyroid hormone, and tumor size. During the treatment, there was no evidence of any side effects. We may conclude that octreotide acetate administration is an effective treatment in patients with TSH-secreting pituitary adenoma for suppressing TSH hypersecretion and reducing the size of the tumor.
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PMID:Reduction in size of a thyrotropin-secreting pituitary adenoma treated with octreotide acetate (somatostatin analog). 803 2

Seven patients with growth hormone (GH)-secreting pituitary adenoma were treated preoperatively with octreotide (Sandostatin or SMS 201-995; a somatostatin analogue), and were compared with 18 non-treated patients in their clinical courses and adenoma analyses. Octreotide treatment improved the endocrinological data in all 7 cases. The octreotide-treated adenomas were soft and easily removed by suction and curettage. The postoperative normalization of endocrinological data was encountered more often in the octreotide-treated cases than in the non-treated, although the statistical significance was not observed by the limited number of cases. The adenoma tissues were examined with conventional histology and immunohistochemistry, and the amount of GH messenger ribonucleic acid (mRNA) was quantitatively assessed. The studies demonstrated: 1) No fibrosis nor necrosis was observed in the adenomas from the octreotide-treated patients. 2) Immunohistochemistry for human GH revealed no remarkable differences between the octreotide-treated and the non-treated adenomas. 3) The amounts of GH mRNA in the adenoma from the octreotide-treated patients were 4.2 +/- 1.8 (mean +/- SEM; expressed in an arbitrary unit) and were significantly less than those from the non-treated (33.6 +/- 9.1). These data suggest that octreotide inhibits not only GH release from the adenoma but also its biosynthesis.
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PMID:Octreotide treatment results in the inhibition of GH gene expression in the adenoma of the patients with acromegaly. 852 60

Functionally active cultures of human pituitary adenoma cells producing excessive amounts of the growth hormone (somatotropinomas), of prolactin (prolactinomas) or of the both hormones (mixed type adenomas) have been prepared and their secreted molecular forms studied. SDS-PAAG electrophoresis combined with immunoblotting making use of poly- and monoclonal antibodies revealed that the growth hormone and prolactin are secreted by adenoma cells in several molecular forms typical of normal human pituitary. The major form secreted by the growth hormone is 22K; the minor forms are 20K (the product of alternative splicing of pre-mRNA) and the split-off two-chain form 25K. The major form secreted by prolactin is 23K; the minor form is glycosylated 25K. No significant differences in the ratios of molecular forms of the hormones were found either under basal conditions of culturing or under the influence of the pituitary function regulators, somatostatin and thyroliberin. At the same time, the data obtained suggest that pituitary adenoma cells can secrete some amount of "abnormal" molecular forms of the hormones, e.g., immature products of postribosomal processing or large-sized immunoreactive fragments. Hence, pituitary adenoma cell cultures are an effective tool in biochemical and physiological studies of molecular forms of the human growth hormone and prolactin and of their secretion.
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PMID:[Molecular forms of human growth hormone and prolactin, secreted by cultured pituitary tumor cells]. 855 61

In the present study, we examined the in vitro and in vivo modulation of IL-1 receptors by stress and endotoxin treatment. The treatment of AtT-20 mouse pituitary adenoma cells for 24 h with neuroendocrine mediators of stress such as CRF and catecholamines produced dose-dependent increases in cAMP production and [125I]IL-1 alpha binding. In contrast, somatostatin and dexamethasone significantly inhibited CRF-stimulated cAMP production and decreased both basal and CRF-mediated increases in [125I]IL-1 alpha binding. Furthermore, in keeping with the effects of stress mediators to up-regulate IL-1 receptors in AtT-20 cells, ether-laparotomy stress in mice resulted in a significant increase in [125I]IL-1 alpha binding in the pituitary with no significant alterations observed in the brain; in contrast, [125I]oCRF binding in the pituitary was significantly decreased after the ether-laparotomy stress. Next, we investigated the modulation of IL-1 beta levels and [125I]IL-1 alpha binding following endotoxin treatment. IL-1 beta levels were dramatically increased in the peripheral tissues (pituitary, testis, and spleen) at 2-6 h after a single LPS injection (30 micrograms LPS/mouse); however, no significant changes were observed in brain (hippocampus and hypothalamus). [125I]IL-1 alpha binding in the pituitary gland, liver, spleen, and testis was significantly decreased at 2 h following a single administration of both low (30 micrograms LPS/mouse) and high (300 micrograms LPS/mouse) doses of endotoxin. [125I]IL-1 alpha binding in the hippocampus was not significantly altered at 2 h by low dose of LPS and was significantly decreased by high-dose administration of LPS (300 micrograms/mouse). Following two LPS injections (at 0 and 12 h), dramatic increases in IL-1 beta concentrations in the hypothalamus, hippocampus, spleen, and testis were observed at 2 h after the second LPS injection; a small but statistically nonsignificant change was evident in the pituitary. Moreover, dramatic decreases in [125I]IL-1 alpha binding were seen after two injections of 30 micrograms LPS/mouse in both central and peripheral tissues. These data provide further support for a role for IL-1 in coordinating brain-endocrine-immune responses to stress and infection.
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PMID:Interleukin-1 receptors in the brain-endocrine-immune axis. Modulation by stress and infection. 859 15


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