Insulin-like growth factor 1 binding protein 3 synthesis by aortic endothelial cells is a function of cell density

Proliferating bovine aortic endothelial cells in culture do not express the insulin-like growth factor 1 binding protein 3 gene, in contrast to the genes encoding binding proteins 2, 4, 5, and 6. The binding protein 3 gene is activated only at cell confluency with continual transcription thereafter, for at least an eight-day post-confluent period, both in the presence or absence of serum. Secretion of protein product into the medium parallels transcription. DNA synthesis is inversely related to the amount of total insulin-like growth factor 1 binding protein 3 in the culture medium. The addition of anti-binding protein 3 antibody to media significantly increases the rate of DNA synthesis by extensively post-confluent cells. These data suggest (1) aortic endothelial cells are an important source of circulating binding protein 3, (2) binding protein 3 has an inhibitory effect upon the growth of endothelial cells, (3) the triggering of binding protein 3 synthesis after confluency suggests a role in maintaining the growth-arrested monolayer state of the cells in vivo.