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)

In more than one third of growth hormone (GH)-secreting pituitary adenomas, a point mutation in the gene for the alpha-chain of the G stimulatory protein (gsp oncogene) causes the constitutive activation of the membrane adenylyl cyclase (AC) resulting in uncontrolled cyclic adenosine monophosphate (cAMP) elevation and GH hypersecretion. Tumors expressing gsp are characterized by high membrane AC activity, elevated intracellular cAMP content, and high rates of GH release in culture medium. The AC activity is not further stimulated by GH-releasing hormone (GHRH) and other specific and non-specific agents, while it is lowered by somatostatin, as the G inhibitory protein (Gi) is normally working. Acromegalic patients bearing adenomas with the gsp mutation do not present with any obvious clinical or epidemiological distinctive features. However, they have smaller tumors in relation to their circulating GH levels, suggesting that the gsp oncogene maintains a high rate of secretory activity in vivo. Most of these patients show paradoxical GH increases to thyrotropin-releasing hormone (TRH), but none to gonadotropin-releasing hormone (GnRH) or an oral glucose tolerance test (OGTT). As with the in vitro data, these patients are not very sensitive to GHRH administration, but are sensitive to the inhibitory action of somatostatin. In our experience, only three of six patients with non-gsp-mutated tumors had lowered serum GH levels during the administration of octreotide (100 micrograms thrice daily for 4 years), while all of six patients with gsp-mutated tumors had serum GH levels suppressed by octreotide treatment. Such a good GH suppressibility by somatostatin makes patients with gsp-mutated tumors the best candidates for medical treatment with somatostatin analogs.
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PMID:GS protein mutations and pituitary tumors: functional correlates and possible therapeutic implications. 876 3

In recent years the demonstration that human pituitary adenomas are monoclonal in origin has provided further evidence that pituitary neoplasia arise from the replication of a single mutated cell in which growth advantage results from either activation of proto-oncogenes or inactivation of tumor suppressor genes. While common oncogenes, such as Ras, are only exceptionally involved, the only mutations identified in a significant proportion of pituitary tumors, and particular in GH-secreting adenomas, occur in the Gsalpha gene (GNAS1) and cause constitutive activation of the cAMP pathway (gsp oncogene). Moreover, pituitary tumors overexpress hypothalamic releasing hormones, growth factors, and their receptors as well as cyclins involved in cell cycle progression. As far as the role of tumor suppressor genes in pituitary tumorigenesis is concerned, reduced expression of these genes seems to frequently occur in pituitary tumors as a consequence of abnormal methylation processes. Although the only mutational change so far identified in pituitary tumors is the gsp oncogene, this oncogene is not associated with a clear phenotype in patients bearing positive tumors. Mechanisms able to counteract the cAMP pathway, such as high sensitivity to somatostatin, and induction of genes with opposite actions, such as phosphodiesterases, CREB end ICER, or instability of mutant Gsalpha, have been proposed to account for the lack of genotype/phenotype relationships.
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PMID:Genetics of pituitary tumors: Focus on G-protein mutations. 1453 May 8

Growth hormone releasing hormone (GHRH) signals via G protein-coupled receptors (GHRH-R) to enhance intracellular Galphas/adenylyl cyclase/cAMP signaling, which in turn has positive effects on GH synthesis and release, as well as proliferation of the GH-producing cells of the anterior pituitary gland. Some GH-producing pituitary tumors express a constitutively active mutant form of Galphas (gsp oncogene). It has been reported that these tumors are more responsive to octreotide therapy. In this study we used a rat GH-producing cell line (GH3) stably transfected with the human GHRH-R cDNA (GH3-GHRHR cells) as a model to study the effects of gsp oncogene on somatostatin (SRIH) receptor subtype 1 and 2 (sst1 and sst2) mRNA levels. Transient transfection of gsp oncogene in GH3-GHRHR cells for 48 h increased intracellular cAMP levels and GH release. Phosphodiesterase (PDE) 4, sst1 and sst2 mRNA levels were increased by G protein mutation as assessed by real-time RT-PCR. Increased PDE mRNA levels in gsp-transfected cells may be a compensatory mechanism to the constitutive activation of cAMP-dependent pathway by G protein mutation and is consistent with reports of higher PDE expression in human pituitary tumor that express gsp. Our data suggest that higher expression of sst1 and sst2 mRNA induced by the gsp oncogene may be a mechanism by which gsp-positive tumors show a greater response to SRIH. GH3 cells permanently transfected with GHRH-R can be used for in vitro studies of actions of GHRH.
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PMID:Effect of gsp oncogene on somatostatin receptor subtype 1 and 2 mRNA levels in GHRH-responsive GH3 cells. 1637 30

KIT protein expression and mutational status of KIT gene in different types of tumours have been intensively studied since Imatinib Mesylate, KIT/PDGFRA tyrosine kinase inhibitor became available. However, only one immunohistochemical study on KIT expression in pituitary adenomas has been published. There are currently no reports on mutational status of KIT gene in pituitary adenomas. We have immunohistochemically investigated KIT expression in 252 pituitary adenomas and found cytoplasmic reactivity in 52.4% and membranous reactivity in 8.3% of all adenomas. There was statistically significant difference in KIT expression between clinically non-functioning, growth hormone- and adrenocorticotroph hormone-producing adenomas. The group with membranous expression was dominated by somatotropinomas and clinically non-functioning adenomas. KIT expression in a subset of adenomas was also confirmed by western blot analysis of 48 adenomas. Immunohistochemical KIT expression was correlated with basic clinical data and in a cohort of acromegalic patients with additional data (somatostatin receptor type 2A expression, response to somatostatin analogue treatment and mutational status of gsp oncogene). Exons 9, 11, 13 and 17 of KIT gene were searched for mutations in the tumours with membranous KIT expression and in a minority of tumours with cytoplasmic KIT expression using denaturing high-performance liquid chromatography and in suspected cases sequencing of one or more exons. No mutations in the examined exons were found. Our results may suggest a role of KIT in the pathogenesis of a subset of pituitary adenomas and point out the need for further research to find out if KIT-reactive adenomas could be sensitive to Imatinib Mesylate.
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PMID:KIT protein expression and mutational status of KIT gene in pituitary adenomas. 2221 31