Dexamethasone reduces steady state insulin-like growth factor I messenger ribonucleic acid levels in rat neuronal and glial cells in primary culture.
Insulin-like growth factor I (IGF-I) mRNA was demonstrated in primary cultures of neuronal and glial cells from rat brain. On Northern blots, a rat IGF-I cDNA probe hybridized to RNA species of 7.5, 1.7, and 0.8-1.2 kilobases in total and poly(A)+ RNA from both cell types. Solution hybridization/RNase protection assays were performed using an antisense riboprobe complementary to the 5'-untranslated region as well as part of the coding region of rat IGF-I mRNA. These studies indicated that two of the previously described three possible alternative 5'-untranslated splicing variants (classes A and C) were expressed in neuronal and glial cells, with class C transcripts predominating. Neuronal cells also possessed extremely low levels of class B transcripts. Treatment of neuronal cell cultures with the synthetic glucocorticoid dexamethasone reduced IGF-I mRNA levels by 60%. Glial cell IGF-I mRNA levels were reduced by dexamethasone by up to 40%. These results suggest that glucocorticoid-induced reductions in IGF-I production could occur at the level of transcription and may underlie some of the actions of glucocorticoids in causing growth retardation and inhibition of cell proliferation.
Adamo
M
M
Diabetes Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Werner
H
H
Farnsworth
W
W
Roberts
C T
CT
Raizada
M
M
LeRoith
D
D
D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D015342:DNA Probes; D003907:Dexamethasone / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D011061:Poly A / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
D015342:DNA Probes; D012333:RNA, Messenger; D013002:Somatomedins; D011061:Poly A; D012313:RNA; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone