Induction of gene expression of the catecholamine-synthesizing enzymes by insulin-like growth factor-I.
The effects of insulin-like growth factor-I (IGF-I) on gene expression and the activities of the three enzymes specific for catecholamine biosynthesis, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT), were determined in bovine adrenomedullary chromaffin cells primary cultured in serum-free medium. The mRNA level of TH was maximally elevated in the presence of IGF-I by 3.1 +/- 0.4-fold after 48 h, DBH by 5.1 +/- 0.3-fold in 24 h, and PNMT by 2.8 +/- 0.5-fold in 72 h. In addition, the activity of TH was increased by 77%, DBH by 70%, and PNMT by 23% in IGF-I-exposed cultures. In the absence of the growth factor, the mRNA levels of TH and DBH were decreased to 45 +/- 10% and 35 +/- 12% of the time-zero control within 48 h while PNMT mRNA was decreased to 82 +/- 5% only after 72 h. When the cells were cotreated with the protein tyrosine kinase inhibitor genistein, DBH induction by IGF-I was suppressed, confirming that the effect is mediated by tyrosine kinase. Cotreatment with the protein kinase A (PKA) inhibitor H89 caused complete reversal of the IGF-I-induced DBH increase and the effects of IGF-I treatment and PKA activation by forskolin were not additive, suggesting that PKA is involved in the signaling initiated by IGF-I in these cells.
Hwang
O
O
Department of Biochemistry, University of Ulsan College of Medicine, Seoul, Korea.
Choi
H J
HJ
D000313:Adrenal Medulla / Q000166:cytology / Q000201:enzymology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D002395:Catecholamines; D004798:Enzymes; D007334:Insulin-Like Growth Factor I; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D010625:Phenylethanolamine N-Methyltransferase; D017868:Cyclic AMP-Dependent Protein Kinases