Regulation of IGF-binding protein-6 by dexamethasone and IGFs in PC12 rat phaeochromocytoma cells.
PC12 rat phaeochromocytoma cells are widely used as a model of neuronal differentiation. They express IGF receptors and are responsive to IGFs. The main IGF-binding protein synthesized by these cells is IGFBP-6. Glucocorticoids induce differentiation of PC12 cells towards a chromaffin phenotype. The effect of dexamethasone on IGFBP-6 levels was therefore studied. Dexamethasone (500 nM) decreased IGFBP-6 protein in conditioned media and mRNA levels to 61 +/- 5% (P < 0.0001) and 34 +/- 14% (P = 0.03) of control levels respectively. Incubation of PC12 cells with IGF-II (100 ng/ml) for 72 h increased IGFBP-6 protein levels in media to 217 +/- 19% of control (P < 0.0001). IGFBP-6 mRNA levels, however, were unchanged. IGF-I had similar effects on IGFBP-6 protein and mRNA levels. IGFs increased cell number by 50-60%, but this was insufficient to explain the increases in protein levels. IGFBP-6 was not released from a cell-associated reservoir or protected from proteolysis by IGFs, excluding these post-translational mechanisms as explanations for the IGF effects on IGFBP-6 levels. The effects of IGF-II and dexamethasone on IGFBP-6 levels were independent. These results indicated that (1) dexamethasone decrease IGFBP-6 at the mRNA level, and (2) IGFs stimulate IGFBP-6 levels by a post-transcriptional mechanism.
Bach
L A
LA
Department of Medicine, University of Melbourne, Austin, Australia.
Leeding
K S
KS
Leng
S L
SL
D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013002:Somatomedins / Q000494:pharmacology*
D005938:Glucocorticoids; D018976:Insulin-Like Growth Factor Binding Protein 6; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D003907:Dexamethasone