Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of somatostatin (SS) on adrenocorticotrophic hormone (ACTH) secretion from COR-L103 cells derived from a human small cell lung carcinoma was examined. SS at 1 microM had no effect on ACTH secretion from the cells on either short-term or long-term incubation. Studies by the reverse transcription-polymerase chain reaction (RT-PCR) showed that mRNA transcripts of the somatostatin receptor (SSTR) 2, SSTR3 and SSTR4 genes were present in COR-L103 cells. Extra bands were obtained by PCR-single strand conformation polymorphism (SSCP) analysis of the SSTR2 gene Sequence analysis of the SSTR2 gene demonstrated one point mutation in codon 188 of TGG for tryptophan to TGA for a stop codon causing loss of 182 C-terminal amino acid residues of SSTR2. The nucleotide sequences of the SSTR3 and SSTR4 genes in COR-L103 cells were normal. Binding studies using 125I-Tyr11-SS-14 showed specific affinity binding sites on COR-L103 cells and mouse pituitary tumor AtT-20 cells. Octreotide acetate suppressed the binding of 125I-Tyr11-SS-14 to these two cell lines, but the Kd of COR-L103 cells (160 nM) was 60-fold higher than that of AtT-20 cells (2.6 nM). Affinity cross-linking studies using 125I-Tyr11-SS-14 gave three bands of 72 KDa, 55 KDa and 32 KDa from AtT-20 cells, but only two bands of 55KDa and 32kDa from COR-L103 cells. These findings suggest that SSTR2 is not expressed in the plasma membranes of COR-L103 cells due to a point mutation, but that this may have no influence on the effect of SS on ACTH secretion.
 ...
PMID:Point mutation of the somatostatin receptor 2 gene in the human small cell lung cancer cell line COR-L103. 776 54

Previous studies have demonstrated an upregulation of interleukin-1 (IL-1) receptors following treatment of mouse AtT-20 pituitary tumor cells with corticotropin-releasing factor (CRF). In the present study, we determined the modulation of IL-1 receptors and adenylate cyclase activity in AtT-20 cultures following treatment with CRF, isoproterenol, forskolin, somatostatin and dexamethasone. CRF, isoproterenol and forskolin dose-dependently increased 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. Parallel modulation of IL-1 receptors by agents that stimulate (CRF, isoproterenol and forskolin) or inhibit (somatostatin) cAMP production in AtT-20 cells suggest the importance of this second messenger in regulating IL-1 receptors.
 ...
PMID:Cyclic AMP-dependent modulation of interleukin-1 receptors in the mouse AtT-20 pituitary tumor cell line. 780 34

Using a combination of polymerase chain reaction and genomic library screening we have cloned a human gene for a subtype of the somatostatin (SST) receptor (SSTR) termed human SSTR5 (hSSTR5), which is located on chromosome 16. The predicted amino acid sequence of hSSTR5 displays 75% sequence identity with a recently identified rat SSTR [Mol. Pharmacol. 42:939-946 (1992)], suggesting that it is the human homologue of this receptor. hSSTR5 consists of a 363-residue polypeptide exhibiting a putative seven-transmembrane domain topology typical of G protein-coupled receptors. The receptor displays considerable sequence identity to hSSTR1 (42%), hSSTR2 (48%), hSSTR3 (47%), and hSSTR4 (46%). Membranes prepared from COS-7 cells transiently expressing the hSSTR5 gene bound 125I-Leu8,D-Trp22,Tyr25-SST-28 (125I-LTT-SST-28) with high affinity and in a saturable manner. SST-14, SST-28, and various synthetic SST peptide agonists produced dose-dependent inhibition of radioligand binding with the following rank order of potency: LTT-SST-28 > SST-28 > D-Trp8-SST-14 > SST-14 approximately RC-160 approximately BIM 23014 > MK-678 > SMS 201-995. hSSTR5 bound SST-28 with a 12.6-fold greater affinity (Ki = 0.19 nM), compared with SST-14 (Ki = 2.24 nM), indicating that the receptor is SST-28 selective. Addition of GTP, guanosine-5'-O-(3-thio)triphosphate, Na+ ions, or pertusis toxin greatly reduced 125I-LTT-SST-28 binding, thereby indicating that hSSTR5 is coupled to pertussis toxin-sensitive G proteins. Both SST-14 and SST-28 displayed dose-dependent inhibition of forskolin-stimulated cAMP accumulation, consistent with functional coupling of the receptor to adenylyl cyclase inhibition. Northern blot analysis of SSTR5 mRNA revealed a 2.4-kilobase transcript in normal rat pituitary and GH3 rat pituitary tumor cells and a 4.0-kilobase transcript in normal human pituitary. Reverse transcriptase polymerase chain reaction revealed expression of the hSSTR gene in fetal human pituitary and hypothalamus but not in human cerebral cortex. In situ hybridization of the rat pituitary showed that SSTR5 mRNA is selectively localized in the anterior lobe. SSTR5 mRNA was not expressed in four human pituitary tumors (somatotroph adenoma, prolactinoma, and chromophobe adenomas) or in a human insulinoma. Although hSSTR5 displays approximately 75% sequence identity with rat SSTR5, the two receptors display significantly different pharmacological profiles, especially with respect to their binding affinities for the SST analogue SMS 201-995.
 ...
PMID:Molecular cloning, functional characterization, and chromosomal localization of a human somatostatin receptor (somatostatin receptor type 5) with preferential affinity for somatostatin-28. 790 5

Acromegaly and hyperprolactinemia have been described in association with polyostotic fibrous dysplasia; the pathogenetic mechanisms involved in the development of the endocrinopathies is unknown. We report a 26-year-old man with polyostotic fibrous dysplasia and hypersecretion of GH and PRL. Plasma GH, PRL, and insulin-like growth factor-I (IGF-I) were elevated. Glucose-non-suppressible plasma GH concentrations, GH responsiveness to TRH and GHRH, and GH suppression after a test-dose of somatostatin, octreotide, and bromocriptine were found. Plasma GHRH levels were within the normal range (< 25 ng/l). Computed tomography of the sella turcica and visual fields were normal. [111In-DTPA-D-Phe1]-octreotide scintigraphy were used to localize a possible tumor; no radioactivity was visualized at the site of the hypothalamus, the pituitary or elsewhere in the body but a considerable accumulation of radioactivity was found in the os frontalis. Therapy with octreotide by continuous sc infusion partially suppressed GH and IGF-I (and normalized PRL). The results suggest that hypersecretion of GH in our patient is not due to a GH-secreting pituitary tumor, eutopic or ectopic hypersecretion of GHRH or autonomous somatotroph function. The origin of the disease in this patient might be an abnormal hypothalamic regulation of somatotrophs and/or an alteration in the transmembrane signalling systems.
 ...
PMID:Acromegaly and hyperprolactinemia in a patient with polyostotic fibrous dysplasia: dynamic endocrine studies and treatment with the somatostatin analogue octreotide. 791 14

Histamine H3 receptors have been identified in rat and guinea-pig pituitary glands and in the mouse pituitary tumor cell line, AtT-20. Histamine H3 receptor agonists are reported to stimulate adrenocorticotropic hormone (ACTH) release from AtT-20 cells, an effect blocked by histamine H3 but not H1 or H2 receptor antagonists. To determine whether negative feedback regulation of the histamine H3 receptor-mediated effect might occur, we tested the effects of steroid treatment upon binding of the agonist [3H]N alpha-methylhistamine to AtT-20 cell membranes. Consistent with feedback regulation, steroid treatment of the cells reduced [3H]N alpha-methylhistamine binding. The effect was dose-dependent and was greatest for glucocorticoids among the steroids tested. As the duration of steroid treatment increased, the amount of [3H]N alpha-methylhistamine binding decreased, to 15% of control at 36 h. However, the effect was not specific for histamine H3 receptors. Somatostatin inhibits ACTH release from these cells and its binding was similarly reduced by steroid treatment. Because steroids have been reported to modulate levels of guanine nucleotide-binding proteins, the lack of receptor specificity could reflect an indirect effect of steroids upon agonist binding and, in fact, we show that [3H]N alpha-methylhistamine binding to these cells, like somatostatin, is pertussis toxin-sensitive. However, steroid treatment does not alter the apparent levels of pertussis toxin substrate in these cells. Whether steroid treatment affects histamine H3 receptors of these cells directly or through some more subtle effect upon the guanine nucleotide-binding proteins to which they couple, the result is a negative feedback loop that attenuates [3H]N alpha-methylhistamine binding to these cells.
 ...
PMID:Steroid-sensitivity of agonist binding to pituitary cell line histamine H3 receptors. 808 74

The prolactin secreting rat pituitary tumor cell line, GH3, expresses high affinity receptors for both vasoactive intestinal peptide (VIP) and somatostatin (SS14). VIP induces prolactin secretion by GH3 cells, an action which is antagonized by SS14. This in vitro model was used to examine the mechanism of action of two synthetic somatostatin analogs, D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-OH (octreotide; SMS 201-995) and cyclo(aminoheptanoyl-Phe-D-Trp-Lys-Thr (benzyl)) (cyclic pentapeptide; CPP). Octreotide and CPP bind to the pituitary somatostatin receptor with lower affinity than does SS14 (KD = 1.3 +/- 1.1; 80 +/- 29; 211 +/- 107 nM for SS14, octreotide and CPP, respectively). SS14 and octreotide were equally effective as inhibitors of VIP-mediated accumulation of cAMP (40% and 45% inhibition, respectively, P < 0.01). SS14 and octreotide also inhibited forskolin-mediated accumulation of cAMP (42% and 40% inhibition of cAMP production, respectively; P < 0.01). The inhibitory action of somatostatin and octreotide on both VIP- and forskolin-mediated cAMP accumulation was blocked by pre-treatment of GH3 cells with pertussis toxin (P < 0.001). Neither SS14 nor octreotide affects the apparent affinity of VIP for its specific receptors on GH3 cells; thus, the inhibitory action of SS14 and octreotide appears to be mediated at the locus of the G-protein-adenylate cyclase complex. In contrast, CPP inhibited VIP-mediated cAMP accumulation slightly, but had no effect on forskolin-mediated cAMP production. Pertussis toxin did not attenuate CPP affects on VIP-mediated cAMP accumulation. However, pre-incubation of GH3 cells with CPP decreased the apparent affinity of receptors for VIP, suggesting that effects of CPP are attributable to interference with VIP binding rather than inhibition at the G-protein-adenylate cyclase complex.
 ...
PMID:Mechanisms of action of long-acting analogs of somatostatin. 809 91

The diagnostic criteria of GH deficiency and acromegaly have been revised in 1990 by the Ministry of Health and Welfare in Japan. According to this criteria, not only the classical type of severe GH deficiency but also partial GH deficiency can be diagnosed and treated. With development of technology, anatomical abnormalities could be seen by MRI and genetic abnormality analysed. For the treatment of patients with GH deficiency, the pen-system has becomes available, which makes the daily injection of GH painless and easy. For the treatment of GH producing pituitary tumor (acromegaly), a long acting analog of somatostatin is now available to reduce the size of the tumor.
 ...
PMID:[Recent progress in diagnosis and treatment of patients with GH deficiency and GH overproduction]. 825 39

The following recent topics on the pathogenesis, unusual cases, treatment and the long-term prognosis of Cushing' Disease were presented and discussed. 1. hyperplasia of ACTH producing pituitary cell. 2. CRH producing tumor. 3. cyclic or periodic ACTH hormonogenesis. 4. pituitary cortisol resistance syndrome. 5. Carney complex and pituitary tumor. 6. GIP and PAH. 7. Superselective cavernous venous sampling. 8. Somatostatin analogue. 9. Results of Hardy' operation in Japan. 10. Long-term prognosis of 372 cases. 11. Opeprim treatment after Hardy's operation.
 ...
PMID:[Cushing's disease]. 825 43

A 48-year-old man with visual disturbances and subtle features of acromegaly had elevated serum thyrotropin (thyroid-stimulating hormone) levels but was clinically euthyroid and initially had normal blood growth hormone (GH) levels. A computed tomographic scan documented a large pituitary tumor; he underwent incomplete transsphenoidal adenomectomy. Postoperative octreotide treatment failed to shrink the tumor. Rising GH levels necessitated repeated transsphenoidal and, subsequently, frontotemporal resection. By histology, the tumor was a chromophobic adenoma. In the first specimen, immunocytochemistry localized GH, beta-thyrotropin, and alpha-subunit of glycoprotein hormones in adenoma cells. The second specimen also contained prolactin, whereas the third contained only GH and beta-thyrotropin. By electron microscopy, the tumor was bimorphous, composed of elongated thyrotrophs and densely granulated somatotrophs. In tissue culture, the first specimen released GH, thyrotropin, and alpha-subunit and smaller quantities of prolactin; the second specimen released only GH and alpha-subunit; and the third released GH, thyrotropin, alpha-subunit, and prolactin. Incubation with somatorelin (GH-releasing hormone) variably stimulated release of all four hormones in the first and third specimens; protirelin (thyrotropin-releasing hormone) had no effect. Somatostatin consistently inhibited release of all four hormones; inhibition by bromocriptine mesylate was variable. The mild degree of clinical and biochemical acromegaly is unusual for a large macroadenoma, and the reasons for the absence of hyperthyroidism are unclear. These discrepancies may be attributed to retarded hormone release and/or synthesis due to suppression by somatostatin in vivo.
 ...
PMID:Recurrent plurihormonal bimorphous pituitary adenoma producing growth hormone, thyrotropin, and prolactin. 828 35

Acromegaly mainly associated with the presence of a growth hormone (GH)-secreting pituitary tumor causes considerable morbidity and carries a risk of premature mortality. Treatment includes surgery, radiotherapy, and the use of dopaminomimetic drugs and somatostatin agonist analogs (octreotide and lanreotide). The use of long-acting somatostatin analogs is limited to adjuvant therapy following failure of surgery and/or radiotherapy and/or bromocriptine. But it may be considered the drug of choice for childhood acromegaly and for syndrome of plurihormonal pituitary overproduction in association with excess GH-releasing hormone (GHRH) and a McCune/Albright-like syndrome. Octreotide has been administered de novo as primary and/or presurgical preparatory therapy. Octreotide doses of 100 to 1500 micrograms were used in two large series in Europe and the United States, which mainly included acromegalics in whom all other modalities had failed (> 65%). Clinical improvement, which was sustained for over 6 months of follow-up evaluation, was reported for more than 50% to 70% of patients. In evaluable patients with visual-field defects, there was a definite amelioration, even if the tumor mass was not reduced, and there was no worsening during therapy; the same is true for the adenoma mass, which showed a variable reduction (median, 15 to 22%). A reduction of serum GH and insulin-like growth factor-1 (IGF-1) levels was found in more than 90% of patients, with GH serum values < 5 ng/mL and IGF-1 serum values < 2 U/mL recorded in 46% and 49%, respectively. Relapse occurred when treatment stopped. Future developments are expected to improve the clinical usefulness of somatostatin analogs.
 ...
PMID:The role of somatostatin agonistic analogs in the treatment of acromegaly. 876


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>