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 impor tant for fetal growth. Human fetal adrenals express abundantly both IG F-II and H19 genes. To clarify the significance and regulation of the H19 gene, we studied its expression in fetal adrenals. In situ hybridi zation experiments showed H19 RNA expression throughout the fetal adre nal cortex, with slightly higher expression in the outer definitive (a dult) than in the inner fetal zone. In primary cultures of fetal adren al cells, ACTH and other activators of the protein kinase-il signal tr ansduction pathway increased both H19 and IGF-II RNA accumulation 1.7- to 10-fold. Staurosporine, a protein kinase-C inhibitor, increased H1 9 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 n ecrosis factor-alpha and interferon-gamma, inhibited H19 and IGF-II RN A accumulation. Transforming growth factor-beta 1 caused a decrease in levels of H19 and IGF-II RNA, whereas the IGFs caused a slight increa se. Our data show parallel multifactorial regulation of H19 and IGF-II RNAs in human fetal adrenal cells. This suggests common regulatory me chanisms for these adjacent genes.