Parallel regulation of parentally imprinted H19 and insulin-like growth factor-II genes in cultured human fetal adrenal cells.
Adjacent, parentally imprinted, insulin-like growth factor-II (IGF-II) and H19 genes are highly expressed during embryogenesis and are important for fetal growth. Human fetal adrenals express abundantly both IGF-II and H19 genes. To clarify the significance and regulation of the H19 gene, we studied its expression in fetal adrenals. In situ hybridization experiments showed H19 RNA expression throughout the fetal adrenal cortex, with slightly higher expression in the outer definitive (adult) than in the inner fetal zone. In primary cultures of fetal adrenal cells, ACTH and other activators of the protein kinase-A signal transduction pathway increased both H19 and IGF-II RNA accumulation 1.7- to 10-fold. Staurosporine, a protein kinase-C inhibitor, increased H19 and IGF-II RNA to the same extent as did ACTH. The protein kinase-C activator 12-O-tetradecanoyl phorbol-13-acetate and cytokines, tumor necrosis factor-alpha and interferon-gamma, inhibited H19 and IGF-II RNA accumulation. Transforming growth factor-beta 1 caused a decrease in levels of H19 and IGF-II RNA, whereas the IGFs caused a slight increase. Our data show parallel multifactorial regulation of H19 and IGF-II RNAs in human fetal adrenal cells. This suggests common regulatory mechanisms for these adjacent genes.
Voutilainen
R
R
Department of Pathology, University of Helsinki, Finland.
Ilvesmäki
V
V
Ariel
I
I
Rachmilewitz
J
J
de Groot
N
N
Hochberg
A
A
D000302:Adrenal Cortex / Q000378:metabolism; D000311:Adrenal Glands / Q000196:embryology* / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D015152:Blotting, Northern; D002478:Cells, Cultured; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005326:Fetal Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D007371:Interferon-gamma / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012313:RNA / Q000378:metabolism; D015398:Signal Transduction; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000470:Alkaloids; D005326:Fetal Proteins; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D007335:Insulin-Like Growth Factor II; D007371:Interferon-gamma; D000324:Adrenocorticotropic Hormone; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate