CHARACTERIZATION OF RECEPTORS FOR INSULIN-LIKE GROWTH-FACTOR TYPE-I ON CULTURED HUMAN ENDOMETRIAL STROMAL CELLS - DOWN-REGULATION BY PROGESTERONE

Because insulin-like growth factor type I (IGF-I) is reputed to be inv olved in the endometrial decidualization, we analyzed the expression o f IGF-I receptors in an in vitro system of human endometrial stromal c ells. Competitive binding studies of both intact stromal cells and mem brane preparation indicated the presence of specific components with h igh affinity for binding ICF-L Half-maximum displacement was obtained with 2.3 nmol/l native ICF-I, whereas insulin was unable to achieve ha lf-maximum displacement even at higher concentrations. This IGF-I bind ing component was found to be a saturable protein in respect of the ra dioligand [I-125]IGF-I, with a dissociation constant of 0.16 nmol/l. A ffinity cross-linking studies revealed a labelled band of approximate relative molecular mass 135000, corresponding to the known alpha-subun it of IGF-I receptor. This band was significantly inhibited dose-depen dently by the IGF-I receptor monoclonal antibody alpha-IR3 or native I GF-I, suggesting that the IGF-I binding component in the membrane of s tromal cells has the identity of the alpha-subunit of IGF-I receptor. Cell proliferation in vitro was stimulated by progesterone. Furthermor e, progesterone downregulated the [I-125]IGF-I binding activity by dow nregulation of the IGF-I membrane receptor of human endometrial stroma l cells. These data show that the IGF-I receptor is a functionally int egral component of the stromal cell membrane structure, and its expres sion might be directly modulated by progesterone and, therefore, might play an important role in the preparation of the stroma for successfu l embryo implantation.