Insulin-like growth factor binding protein-4, -5 and -6 mRNAs in the human fetus: localization to sites of growth and differentiation?

The insulin-like growth factor binding proteins (IGFBP) modulate the regulatory actions of insulin-like growth factors (IGF) on fetal growth and development. We have determined the sites of IGFBP-4, -5 and -6 synthesis in 14-18 weeks gestation human fetal tissues using northern blot analysis and in situ hybridization to localize their mRNAs. IGFBP-4, -5 and -6 mRNAs were present in most fetal tissues at this gestational age. IGFBP-4 mRNA (2.3 kb) was widely expressed, most abundantly in kidney, stomach, intestine and lung and least in the liver. IGFBP-5 mRNA (6 kb) was in highest abundance in muscle, skin, stomach and intestine. IGFBP-6 mRNA (1.4 kb) was expressed with greatest abundance in the heart, muscle and skin and least in the liver. In situ hybridization confirmed the widespread occurrence of these mRNAs. The distribution of all three IGFBP mRNAs was similar in each tissue with variations in relative abundance between different regions. In general, IGFBP-4, -5 and -6 mRNAs were prevalent in regions of active cellular division and differentiation, suggesting that the binding proteins they encode specify the sites of IGF activity in the developing fetus. The widespread occurrence of their mRNAs suggests that, like IGFs, they are synthesized in multiple tissues in the fetus and have an autocrine or paracrine mode of action.