CELLULAR-LOCALIZATION OF INSULIN-LIKE-GROWTH-FACTOR-II MESSENGER-RNA IN THE HUMAN FETUS AND THE PLACENTA - DETECTION WITH A DIGOXIGENIN-LABELED CRNA PROBE AND IMMUNOCYTOCHEMISTRY

IGF-II plays a major role in the regulation of human fetal growth and development. However, more extensive information on the cellular sites of IGF-II synthesis in the fetus would provide more insight into its role in fetal organogenesis. Thus we have determined the sites of IGF- II synthesis in 18-26-wk gestation human fetal tissues using in situ h ybridization with a digoxigenin-labeled cRNA probe to localize IGF-II mRNA in fetal liver, kidney, adrenal gland, cerebral cortex, costal ca rtilage, skeletal muscle, and lung, and in placental tissue. In human fetal tissues it has to date been impossible to clearly assign IGF-II mRNA to epithelial cells of entodermal origin. Besides their already k nown localization in cell matrix and a variety of mesodermal cell type s, strong IGF-II mRNA-positive signals were detected in epithelial cel ls in the liver (hepatocytes), bronchial and bronchiolar epithelium, u ndifferentiated renal tubular epithelium,mature glomerular epithelium, pelvic urothelium, and adrenal epithelial cells of the zona persisten s. To identify the cellular location of immunoreactive IGF-II, we also performed immunocytochemical studies in tissues of the same fetuses. Every tissue studied except the cerebral carter contained immunoreacti ve cells; however, immunostaining was generally weaker than in situ hy bridization signals, Our data show that the distribution of IGF-II in human fetal tissue is much more widespread than hitherto thought. A di goxigenin-labeled detection system for IGF-II is more capable of detec ting the cellular expression pattern of IGF-II than radioactive probes and is suitable for analysis of routinely prepared paraffin-embedded material.