Linked Life Data

9025720

Source:http://linkedlifedata.com/resource/pubmed/id/9025720

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1997-3-10
pubmed:abstractText
Low levels of insulin-like growth factor I (IGF-I) in critical illness are observed despite increased or normal levels of growth hormone (GH). The mechanisms for this apparent GH resistance have not been elucidated. As many of the acute inflammatory responses in critical illness are mediated by the proinflammatory cytokines interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), the present studies evaluated IL-1 beta and TNF-alpha effects on steady-state and GH-stimulated IGF-I synthesis and GH receptor mRNA levels. In rat hepatocytes in primary culture, IGF-I released into culture medium was determined by radioimmunoassay, and quantitative competitive polymerase chain reaction was used to measure IGF-I mRNA and GH receptor mRNA concentrations. Growth hormone increased GH receptor mRNA, IGF-I mRNA and IGF-I protein secreted into the culture medium. In cells not stimulated with GH, modest inhibitory effects of IL-1 beta on GH receptor mRNA, IGF-I mRNA and IGF-I protein levels were seen. However, the stimulatory effects of GH were inhibited in a dose-dependent manner both by IL-1 beta and TNF-alpha, and at higher cytokine concentrations no stimulatory effects of GH were observed. Both IL-1 beta and TNF-alpha in submaximal dose had additive inhibitory effects on IGF-I protein concentrations but these effects did not result in irreversible damage to cells, as indicated by restoration of IGF-I and GH receptor mRNA levels to normal after withdrawal of cytokines. In conclusion, we demonstrated that in rat hepatocytes in primary culture IL-1 beta and TNF-alpha inhibited GH-stimulated IGF-I synthesis. Diminished GH receptor mRNA concentrations in response to IL-1 beta and TNF-alpha indicate that low IGF-I levels during severe illness, despite high circulating GH levels, may at least partially be a consequence of suppression of hepatic GH receptor synthesis by IL-1 beta and TNF-alpha.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0804-4643
pubmed:author
pubmed:issnType
Print
pubmed:volume
135
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
729-37
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9025720-Animals, pubmed-meshheading:9025720-Base Sequence, pubmed-meshheading:9025720-Cells, Cultured, pubmed-meshheading:9025720-DNA Primers, pubmed-meshheading:9025720-Dose-Response Relationship, Drug, pubmed-meshheading:9025720-Gene Expression Regulation, pubmed-meshheading:9025720-Human Growth Hormone, pubmed-meshheading:9025720-Humans, pubmed-meshheading:9025720-Insulin-Like Growth Factor I, pubmed-meshheading:9025720-Interleukin-1, pubmed-meshheading:9025720-Liver, pubmed-meshheading:9025720-Male, pubmed-meshheading:9025720-Polymerase Chain Reaction, pubmed-meshheading:9025720-Proteins, pubmed-meshheading:9025720-RNA, Messenger, pubmed-meshheading:9025720-Radioimmunoassay, pubmed-meshheading:9025720-Rats, pubmed-meshheading:9025720-Rats, Wistar, pubmed-meshheading:9025720-Receptors, Somatotropin, pubmed-meshheading:9025720-Recombinant Proteins, pubmed-meshheading:9025720-Tumor Necrosis Factor-alpha
pubmed:year
1996
pubmed:articleTitle
Proinflammatory cytokines interleukin 1 beta and tumor necrosis factor alpha inhibit growth hormone stimulation of insulin-like growth factor I synthesis and growth hormone receptor mRNA levels in cultured rat liver cells.
pubmed:affiliation
Medizinische Kernklinik und Poliklinik, Universitats-Krankenhaus Eppendorf, Hamburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't