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)

Utilizing histones as a substrate and measuring the production of labelled phosphoserine from [gamma 32P-ATP], cAMP stimulated protein kinase activity was found in islet and anterior pituitary secretory vesicles. Cyclic AMP (5 X 10(-7)m)stimulated islet secretory vesicle protein kinase activity as evidenced by a net increase of 32P incorporation into phosphoserine 7.35 +/- 1.68 pmoles/micrograms, (P LESS THAN 9001). Somatostatin (0.1 ng/microgram) decreased 32P phosphoserine production from 10.64 +/- 1.72 to 5.61 +/- 1.26 pmoles/microgram (Pless than .01) by suppressing cAMP stimulated protein kinase activity. In pituitary secretory vesicles, cAMP (5 X 10(-6M) increased 32P incorporation into TCA precipitable protein from 127.3 +/- 8.6 to 202.6 +/- 12.5 pmoles/microgram, P less than .001. With somatostatin (0.2 ng/microgram) there was 55.25+/- 1.95% inhibition of cAMP stimulated protein kinase activity, (P LESS THAN .001). Somatostatin did not inhibit cAMP stimulated protein kinase activity in erythrocyte membrane ghosts nor did somatostatin inhibit the partially purified cAMP dependent protein kinase from cardiac muscle. These data suggest that either (1) a specific somatostatin sensitive dependent protein kinase is present in islet and anterior pituitary secretory vesicles or (2) that a somatostatin receptor is present in these tissues which allows somatostatin to act selectively at these sites. Somatostatin may act by inhibiting the cAMP dependent protein kinase enzme in certain key tissues or subcellular organelles.
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PMID:Somatostatin: selective inhibition of cyclic AMP stimulated protein kinase. 22 50

Isolated sheep thyroid follicles release specific insulin-like growth factor-binding proteins (IGFBPs). Since IGFBPs can modulate IGF bioactivity, at least in vitro, their presence in thyroid tissue may influence synergistic interactions between TSH and endogenous IGF-I or -II which are known to control both thyroid growth and function. We have examined the hormonal control of IGFBP release in relation to iodine organification. Sheep thyroid follicles were isolated by incubation with collagenase and differential centrifugation, grown in Coon's modified Ham's F12M medium with the addition of transferrin, glycylhistidyl-lysine, somatostatin (3H), TSH, cortisol and insulin (6H), and maintained in OH (hormone-free) or 3H medium with or without further supplements for 48 h. Conditioned culture medium was separated by 8% sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis, transferred to nitrocellulose and incubated with 125I-labelled IGF-II followed by autoradiography (ligand blot). Additionally, the radioactive bands were cut from the filters and quantified by gamma-spectrometry. Iodine organification was assessed by incubation of follicles with 10(6) c.p.m. Na125I for 3 h before washing, solubilization in 0.1 mol NaOH/l and the precipitation of organified radioisotope with 10% (v/v) trichloroacetic acid. Cells conditioned in OH or 3H medium released specific IGFBPs of 46, 34, 28 and 19 kDa on ligand blot analysis. The proteins of 34 and 19 kDa were immunopositive on Western blot analysis using anti-bovine IGFBP-2 antiserum. The 46-kDa IGFBP was retained by Concanavalin A-Sepharose chromatography and demonstrated to be glycoprotein. This is probably ovine IGFBP-3. The addition of TSH, or TSH plus cortisol to OH or 3H medium significantly decreased the 125I-labelled IGF-II associated with the 34- and 28-kDa IGFBP species. All IGFBP species were substantially reduced in 6H medium, which was predominantly due to the effects of TSH and cortisol. When total 125I-labelled IGF-II associated with IGFBPs was considered, a significant (P less than 0.01) inverse correlation existed between IGFBP activity and iodine organification in the same cultures; the latter being greatest in OH or 3H medium supplemented with TSH and cortisol. None of these hormone additions altered the endogenous release of IGF-II by the cells. These results suggest that endogenous IGFs, under hormonal control, may modulate the action of endogenous IGF in the regulation of thyroid function.
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PMID:Hormonal regulation of insulin-like growth factor (IGF)-binding proteins secreted by isolated sheep thyroid epithelial cells: relationship with iodine organification. 171 78

Somatostatin (SRIF) inhibits calcitonin and T3-T4 secretion in thyroid. We have investigated the in vitro effect of SRIF on the basal and TSH induced [3H]thy incorporation, thyroglobulin (tgb) RNA and cAMP level in follicular cells, isolated from normal and adenomatous human thyroids. [3H]thy uptake has been evaluated as TCA-precipitable material in 2, 4, 8, 24 h incubated follicles and 24 h incubated adherent cells. Tgb RNA has been quantified with cytoplasmic dot blot hybridization and cAMP level with RIA method. SRIF reduces basal and TSH-induced [3H]thy in both suspension follicles and epithelial adherent cells. However it does not modify tgb RNA nor cAMP levels in incubated follicles. These data suggest a direct antiproliferative effect of SRIF on human thyroid.
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PMID:[Effects of somatostatin on human thyroid folliculi in vitro]. 196 42

The influence of membrane depolarization on somatostatin secretion and protein synthesis by fetal and neonatal cerebrocortical neurons was studied. Cortical cells obtained by mechanical dispersion were maintained as monolayer cultures for 8 days. The ability of fetal cerebrocortical and hypothalamic cells to release immunoreactive somatostatin (IR-SRIF) was confirmed. Total protein synthesis was determined by the incorporation of [3H]phenylalanine into trichloroacetic acid-precipitable proteins. To study the effect of acute depolarization on protein synthesis, cells were incubated for 30 min with [3H]phenylalanine or [3H]leucine and the depolarizing agent. In fetal cerebrocortical cells, potassium (30 and 56 mM) decreased protein synthesis and RNA levels and increased IR-SRIF release. Depolarization by veratridine, a sodium channel activator, induced a similar effect. The effect of veratridine on IR-SRIF and protein synthesis was reversed by tetrodotoxin, a sodium channel blocker, or verapamil, a calcium channel blocker. These findings suggest that protein synthesis by cerebrocortical cells is decreased in fetal brain cells by membrane depolarization and is dependent on Na+ and Ca2+ entry into cells. In postnatal (day 7) cerebrocortical cells, depolarization induced by high potassium concentrations led to a concomitant increase in protein synthesis, RNA content, and somatostatin release. These findings indicate that depolarization of the cellular membrane is coupled to an increase in protein synthesis in neonatal, but not in fetal, dispersed brain cells.
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PMID:Divergent effects of acute depolarization on somatostatin release and protein synthesis in cultured fetal and neonatal rat brain cells. 246 35

Thyroid hormone (TH) action on somatostatin (SRIF) secretion and synthesis by fetal rat brain cells in culture was studied. Cortical and hypothalamic brain cells were maintained as monolayer cultures for 7-10 days. T3, T4, and [3H] phenylalanine [( 3H]Phe) (40 microCi/plate) were added simultaneously for 48 h. Alternately, cultures were pulse labeled with [3H] Phe for only the last 3 h, after being exposed to TH for 45 h. 3H-Labeled SRIF-like material [( 3H]IR-SRIF) was purified by immunoaffinity chromatography and further characterized by gel filtration in Bio-Gel P-10. Total protein synthesis was determined by the incorporation of [3H]Phe into trichloroacetic acid precipitable proteins. Forty eight-hour T3 treatment had a biphasic effect on secretion of IR-SRIF by both cortical and hypothalamic cells. In cortical cells, low doses of T3 (10(-11) M) significantly increased (P less than 0.01) and high T3 doses (10(-7) M) significantly decreased (P less than 0.05) total IR-SRIF (nanograms per plate); control: 2 +/- 0.25; T3 (10(-11) M): 3 +/- 0.3; T3 (10(-7) M): 1.3 +/- 0.1. Similarly, T4 had a significant stimulatory action at 10(-9) M, being inhibitory at 10(-7) M (picograms/plate); control: 290 +/- 20 T4 (10(-9) M): 510 +/- 40; T4 (10(-7) M): 201 +/- 10. When [3H]Phe was added during the 48 h of the experiment, [3H]IR-SRIF synthesis in response to T3 by cortical cells significantly increased after exposure to 10(-11) M (P less than 0.05) and decreased with 10(-7) M (P less than 0.05). When [3H]Phe was added for only the last 3 h or incubation with T3, the action was inhibitory at both 10(-11) M and 10(-7) M. Trichloroacetic acid precipitable material decreased in a dose response manner between T3, 10(-11) M and 10(-7) M. These findings suggest that at this time of brain development, SRIF synthesis by cortical and hypothalamic cells is affected by TH.
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PMID:Thyroid hormone action on biosynthesis of somatostatin by fetal rat brain cells in culture. 289 3

Regulation of glycosylation of TSH was studied in primary cultures of normal rat pituitary cells. [3H]Glucosamine or [3H]proline incorporation into immunoprecipitable TSH and trichloroacetic acid-precipitable proteins was measured after incubation periods ranging from 4-72 h. TSH release was assessed by RIA of TSH in the medium. TRH (30 nM) specifically increased the glycosylation of TSH despite the fact that it did not stimulate [3H]proline incorporation into the hormone even after 72 h of continuous labeling. The TRH-stimulated [3H]glucosamine-labeled TSH was completely recovered in the incubation medium. Effective concentrations of TRH were in the same range as those necessary for stimulation of TSH release (10(-10) - 10(-6) M). Somatostatin (50 nM) and T3 (10 microM) antagonized TRH effects on both TSH release and glycosylation. Stages of TSH glycosylation were discriminated by the addition to the culture medium of tunicamycin (10 micrograms/ml) or monensin (25 microM), which are known to inhibit core and terminal glycosylation of proteins, respectively. Medium [3H]glucosamine-labeled TSH was fully glycosylated, whereas a large part of the intracellular hormone was only core glycosylated. This suggests that terminal glycosylation of TSH could be related to hormone secretion. TRH stimulated essentially only terminal glycosylation of TSH. No alteration of core glycosylation of the hormone was observed after TRH treatment. The stimulating effect of TRH on terminal glycosylation of TSH is probably related to its ability to stimulate hormone release.
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PMID:Control of thyrotropin glycosylation in normal rat pituitary cells in culture: effect of thyrotropin-releasing hormone. 640 87

The ability of TSH to stimulate synthesis and release of thyroid hormones in ovine thyroid follicles in vitro depends partially on a synergy with insulin-like growth factors (IGFs). The cellular availability of IGFs may be influenced by the release of several IGF binding proteins (IGFBPs). The purposes of these studies was to 1) further characterize the species of IGFBPs synthesized by thyroid follicles, 2) examine the ability of TSH and cortisol to alter IGFBP gene expression and protein release, and 3) investigate the actions of exogenous IGFBPs on thyroid cell function. Adult sheep thyroid follicles were isolated after collagenase digestion, grown to confluence in Coon's modified Ham's F12M medium (OH) with the addition of transferrin, glycylhistidyl-lysine, somatostatin (3H), cortisol and insulin, and maintained in serum-free test media with or without further supplements for up to 48 h. Conditioned media were analyzed for IGFBP presence by Western ligand blotting, and by immunoblotting using specific antisera against bovine IGFBP-2 and human IGFBP-5. IGFBP mRNAs from follicles were identified by Northern blot hybridization using [32P]labeled complementary DNAs encoding ovine IGFBP-1 or -2, and rat IGFBP-4, -5, or -6. Uptake and organification of Na[125I] were measured by incorporation into trichloroacetic acid-precipitable material. Isolated thyroid follicles synthesized four species of IGFBPs in either 0H or 3H medium as detected by ligand blotting, of sizes 40-46, 34, 28, and 18 kilodaltons (kDa), respectively. The 32 kDa IGFBP was identified immunologically as IGFBP-2, whereas the 28 kDa and 18 kDa species were identified as IGFBP-5. Northern blot hybridization of total RNA from cells in 3H medium demonstrated an IGFBP-2 messenger RNA (mRNA) [1.4 kilobase (kb)], an IGFBP-4 mRNA (2.6 kb), and two IGFBP-5 mRNAs (6 kb and 1.8 kb). No IGFBP-1 or -6 mRNAs were detected. Incubation of cultured follicles with TSH (30-500 microU/ml) caused a dose-dependent decrease in the abundance of all IGFBP mRNAs and released proteins, which were reduced further by TSH together with cortisol (10 nM). When the inhibitory effect of TSH and cortisol was removed, IGFBP-2 mRNA increased within 3 h and was 7-fold greater within 12 h. IGFBP-2 did not appear in the conditioned medium until 12 h after TSH removal, along with the other IGFBP species.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hormonal regulation and biological actions of insulin-like growth factor binding proteins in isolated ovine thyroid follicles. 750 36

The mechanisms by which somatostatin exerts its widespread inhibitory actions have been investigated extensively but understood only partially. Recent studies have shown that somatostatin can inhibit gene transcription directly. In view of the critical importance of early response genes in induction of gene expression, we examined whether the action of somatostatin might be mediated by inhibition of early response genes. The products of some of these genes, such as c-fos and c-jun, are known to form a heterodimeric transcription factor complex (AP-1) that binds specifically to the consensus sequence TGAC(G)TCA. Accordingly, we examined the effects of somatostatin on c-fos gene expression and on the binding of the AP-1 complex to its specific DNA element using isolated gastric parietal cells and the GH3 pituitary cell line. In both parietal and GH3 cells, c-fos-specific mRNA was increased by agents known to act via both adenosine-3',5'-cyclic monophosphate and Ca(2+)-dependent signaling mechanisms, and octreotide significantly inhibited this response. Pertussis toxin pretreatment (200 ng/ml) reversed the inhibitory effect of octreotide. AP-1 binding activity, assessed by gel shift assays using a 32P-labeled AP-1 oligonucleotide probe, was stimulated by dibutyryl adenosine 3',5'-cyclic monophosphate and serum and inhibited by octreotide treatment. Our observations support the notion that the universal inhibitory action of somatostatin may be mediated by inhibition of expression of early response genes via a pertussis toxin-sensitive inhibitory pathway. This effect appears to lead to decreased binding of regulatory nuclear proteins to their specific DNA elements resulting, presumably, in diminished gene expression.
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PMID:Molecular basis for somatostatin action: inhibition of c-fos expression and AP-1 binding. 791 96

In this study, we report the binding constants (Kd) of the cAMP-responsive element binding protein (delta-CREB) for various cAMP-response element (CRE) motifs. We utilized purified recombinant delta CREB protein in binding reactions with natural CRE motifs found in the promoter of two neuropeptide hormone genes and with several variant CRE motifs. The Kd of delta CREB for the perfectly palindromic CRE, TGACG-TCA, found within the somatostatin promoter is estimated to be 5.0 x 10(-9) M. The Kd of delta CREB for the variant CRE motif TG_CGTCA found within the enkephalin promoter is calculated to be in the 3 x 10(-8) M. These studies provide an in vitro quantitative assessment of the binding affinity of delta CREB for various CRE motifs.
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PMID:Binding constant determination studies utilizing recombinant delta CREB protein. 847 Nov 66