EXPRESSION OF EPIDERMAL GROWTH-FACTOR, TRANSFORMING GROWTH-FACTOR-ALPHA, AND THEIR COMMON RECEPTOR GENES IN HUMAN UMBILICAL CORDS

Epidermal growth factor (EGF) and transforming growth factor-cu (TGF a lpha), present in amniotic fluid and/or in fetal blood, could potentia lly regulate cord functions. The present study investigated the possib le presence of functional receptors and EGF and TGF alpha themselves i n umbilical cord. The reverse transcription-polymerase chain reaction followed by Southern blotting demonstrated that human umbilical cords contain EGF, TGF alpha, and EGF/TGF alpha messenger ribonucleic acid ( mRNA) transcripts. In situ hybridization revealed that these mRNA tran scripts are present in vascular endothelial cells and smooth muscle, a mnion, and myofibroblasts in Wharton's jelly. Western immunoblotting s howed that the cords contain a 170-kilodalton EGF/TGF alpha receptor p rotein. Immunocytochemistry demonstrated that all of the cells that co ntained mRNA transcripts also contained corresponding proteins. Umbili cal amnion contains more EGF, TGF alpha, and their receptors than any other part of the cord. In the cord, the fetal and middle portions con tain more than the placental portion or the vessels inside the placent al tissue. The cord receptors can bind [I-125]EGF, stimulate receptor autophosphorylation, and increase cyclooxygenase-1 and -2 and prostagl andin E(2), suggesting that the receptors are functional. In summary, our study demonstrates that human umbilical cord expresses EGF, TGF al pha, and their common receptor genes. The cord EGF/TGF alpha receptors are functional in terms of binding of EGF, activation of receptor aut ophosphorylation, and increasing the formation of vasoconstrictive eic osanoid. Thus, EGF, TGF alpha, and their receptors could be one of the determinants of human fetal growth and development by autocrine, para crine, and endocrine actions in umbilical cord.