Characterization of receptors for insulin-like growth factor type I on cultured human endometrial stromal cells: downregulation by progesterone.

Abstract

Because insulin-like growth factor type I (IGF-I) is reputed to be involved in the endometrial decidualization, we analyzed the expression of IGF-I receptors in an in vitro system of human endometrial stromal cells. Competitive binding studies of both intact stromal cells and membrane preparation indicated the presence of specific components with high affinity for binding IGF-I. Half-maximum displacement was obtained with 2.3 nmol/l native IGF-I, whereas insulin was unable to achieve half-maximum displacement even at higher concentrations. This IGF-I binding component was found to be a saturable protein in respect of the radioligand [125I]IGF-I, with a dissociation constant of 0.16 nmol/l. Affinity cross-linking studies revealed a labelled band of approximate relative molecular mass 135000, corresponding to the known alpha-subunit of IGF-I receptor. This band was significantly inhibited dose-dependently by the IGF-I receptor monoclonal antibody alpha-IR3 or native IGF-I, suggesting that the IGF-I binding component in the membrane of stromal cells has the identity of the alpha-subunit of IGF-I receptor. Cell proliferation in vitro was stimulated by progesterone. Furthermore, progesterone downregulated the [125I]IGF-I binding activity by downregulation of the IGF-I membrane receptor of human endometrial stromal cells. These data show that the IGF-I receptor is a functionally integral component of the stromal cell membrane structure, and its expression might be directly modulated by progesterone and, therefore, might play an important role in the preparation of the stroma for successful embryo implantation.