Receptor-mediated processing of epidermal growth factor in the trophoblast of the human placenta.
The processing of epidermal growth factor (EGF) and its receptor in human trophoblast during the first trimester and at term was studied using biotin-labeled EGF, an anti-EGF receptor monoclonal antibody and immunohistochemistry. In chorionic villi incubated with EGF-biotin the ligand was first bound to specific receptors on the syncytial surface, which are in contact with the maternal blood. After 2-5 min in the early gestation placenta, EGF-biotin was found at the basal plasma membrane of the syncytium accompanied by a pronounced EGF receptor immunostaining. In contrast, in the term placenta, immunostaining of EGF-biotin as well as EGF receptors was pronounced in the syncytioplasma within 30-60 min following EGF stimulation; in addition, EGF-biotin was found in some syncytial nuclei. These immunostaining reactions were enhanced after lysosomal blockage by chloroquine. The results reveal a transsyncytial, receptor-mediated transfer of EGF from the maternal blood to the cytotrophoblast, the proliferating part of the trophoblast, in the first trimester placenta. However, in the term placenta, the EGF signal seems to be directed primarily to the syncytium, thus probably influencing differentiated functions. In conclusion, the trophoblast examplifies three possible pathways of EGF processing: 1. transcytotic transfer, 2. direct intracellular signalling followed by lysosomal degradation, and 3. nuclear binding.
Institute of Pathology, Medical University of Lübeck, Federal Republic of Germany.
H
H
Arnholdt
J
J
Diebold
B
B
Kuhlmann
U
U
Löhrs
D001692:Biological Transport; D001710:Biotin; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008431:Maternal-Fetal Exchange / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D014327:Trophoblasts / Q000502:physiology*
D004815:Epidermal Growth Factor; D001710:Biotin; D066246:ErbB Receptors