Regulation of human IGF-II transcription in fetal and adult tissues.

The insulin-like growth factors are single-chain polypeptides which promote cell multiplication in vitro. Their role in mammalian development is uncertain, although they have been implicated as modulators of cell growth and differentiation. We present evidence that the human IGF-II gene has at least two promoters, and their expression may be developmentally controlled in the liver. Most of the IGF-II transcripts in the fetal organs examined are derived from a promoter which is different to that used for most adult liver IGF-II mRNAs. Steady-state levels of IGF-II transcripts are seen to be dramatically reduced in organs of adult rather than fetal origin. This observation is apparently not linked to promoter usage and therefore suggests a second level of transcriptional control. In addition, we show that an alternative splicing event at an intron/exon boundary, which results in an mRNA with an altered coding potential, is not developmentally regulated. This variant IGF-II mRNA is coexpressed with the major species of IGF-II at a low, but constant, ratio in all fetal and adult organs examined.