Tri-iodothyronine and cycloheximide enhance insulin-like growth factor-binding protein-1 gene expression in human hepatoma cells.
The growth-regulating actions of IGFs are modulated by their binding proteins (IGFBPs). The serum concentration of IGFBP-1 is down-regulated by insulin, and in-vitro studies have demonstrated that IGFBP-1 secretion from various tissues and cells can be stimulated by theophylline, forskolin, oestrogen and progesterone. We have studied the effects and mechanisms of thyroid hormone action on IGFBP-1 gene expression and secretion by human hepatoma cells in vitro. Tri-iodothyronine dose-dependently enhanced IGFBP-1 secretion in serum-free HepG2 cell cultures after 24-48 h of exposure, as measured by a specific immunofluorometric assay. This was accompanied by an increase (+ 50%) in the amount of IGFBP-1 mRNA, which could be prevented by cycloheximide, a protein synthesis inhibitor. Cycloheximide transiently enhanced (+ 200%) the accumulation of IGFBP-1 mRNA at 3-12 h of incubation, when no effect of tri-iodothyronine was observed. It is concluded that thyroid hormone stimulates IGFBP-1 secretion slowly by enhancing IGFBP-1 gene expression by a protein mediator. The acute stimulation of IGFBP-1 gene transcription by cycloheximide associates this gene with a number of growth-related genes encoding growth- and tumour-associated peptides.
Angervo
M
M
Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Finland.
Leinonen
P
P
Koistinen
R
R
Julkunen
M
M
Seppälä
M
M
D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology*
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D013002:Somatomedins; D014284:Triiodothyronine; D003513:Cycloheximide