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 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

The cAMP-response element-binding protein (CREB) transcription factor was initially identified as a mediator of cAMP-induced gene expression. CREB binds to a target sequence termed the cAMP-response element (CRE) found in many cellular and viral gene promoters. One of the best-characterized CREs resides in the promoter of the gene encoding the neuropeptide somatostatin, and this element has served as a model for studies of CREB function. Phosphorylation of CREB by protein kinase A allows recruitment of the coactivator CREB-binding protein (CBP). A central tenet of the CREB-CBP model is that CREB binds constitutively to the CRE and that regulation occurs through the phosphorylation-dependent recruitment of CBP. In this report, we use chromatin immunoprecipitation assays to show that CREB does not interact in vivo with the somatostatin CRE, or similar elements in several other genes, in PC12 cells, a standard model for studies of CREB function. Rather, CREB binding in vivo is regulated in a cell-specific manner, a finding that was confirmed by using in vivo genomic footprinting assays. The CREs in other genes were also found to interact differentially with CREB in PC12 cells, hepatoma cells, and cortical neurons. We conclude that the family of CREB target genes differs from one cell type to another and that the ability of CREB to bind to a particular CRE represents an important component of gene regulation.
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PMID:Cell-type-specific binding of the transcription factor CREB to the cAMP-response element. 1534 15

Growth hormone (GH) declines during aging. This study investigates whether pituitary constitutive alterations may be involved in the GH decline. Two groups of male Wistar rats were studied (young: 3-month-old; old: 24-month-old). The old rats showed lower pituitary GH messenger RNA (mRNA) levels, immunoreactive rat (IR)-GH content, and GH secretion with no difference in pituitary Pit-1 and cAMP-response element-binding protein (CREB) expression. Pituitary GH releasing hormone receptor (GHRH-R), GH secretagogue receptor (GHS-R), sstr2, and sstr5 mRNA levels were significantly reduced in old rats. The percentage of GH immunoreactive cells was similar in both groups. In vitro, pituitary IR-GH response to GHRH, forskolin (FK), ghrelin, and insulin-like growth factor I (IGF-I) was similar when compared with respective basal secretion and somatostatin-diminished GHRH- and ghrelin-induced IR-GH release in both groups. These results indicate that, as somatotrope function is maintained in aging, the changes observed in GH gene expression and secretion could be reversed by GHS.
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PMID:Pituitary alterations involved in the decline of growth hormone gene expression in the pituitary of aging rats. 1759 14


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