Dexamethasone Reduces Steady State Insulin-Like Growth Factor I Messenger Ribonucleic Acid Levels in Rat Neuronal and Glial Cells in Primary Culture

Abstract

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.