Human Endometrium Insulin-like Growth Factor I Receptors in Normal and Neoplastic

Insulin-like growth factor I (IGF-I) binding sites were characterized in normal and neoplastic endometrium. The characteristics of the endometrial IGF-I receptor are similar to those reported for other tissues. The binding of I25I-IGF-I to the endometrial membranes is saturable and time, temperature, and pH dependent. The I25I-IGF-I binding activity to the membranes obtained from differentiated and undifferentiated adenocarcinoma as well as sarcoma of the endometrium was significantly higher (P < 0.05) when compared to the binding activity of the membranes obtained from normal endometrium. The Scatchard analysis of the com petitive binding data of both normal and neoplastic endometrium revealed linear plots. This indicated a single class binding site for IGF-I with equilibrium dissociation constants (A,,)of 5.0, 6.8, 6.94, and 6.88 MMfor normal, differentiated, and undifferentiated adenocarcinoma, and sarcoma of the endometrium, respectively. Therefore, the differences observed in 125I-IGF-I binding between normal and neoplastic endometrial mem branes was due to an increase in the number of IGF-I binding sites and not to a change in receptor binding affinity. Autoradiograms from affinity labeling studies revealed a band corresponding to M, 132,000 subunit of the receptor which is characteristic of the type I receptor reported for other tissues. A dimer of the a subunit (M, 263,000) was also observed in all four categories of endometrial tissue. Additionally, autoradiograms obtained from sarcoma of the endometrium revealed a M, 40,000 band that was only displaced by IGF-I and IGF-II peptides but not by the monoclonal antibody a IR-3 to the type I receptor. These suggest that the band is representative of the IGF-I or IGF-II binding protein. A similar band was not observed in the other tissues. The results show that the human endometrium contains high affinity IGF-I or IGF-II binding sites. The fact that IGF-I binding activity was significantly higher for neoplastic endometrium suggests that IGF-I may play an important role on supporting the growth of this neoplastic tissue.