INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 INHIBITS THE MITOGENIC EFFECT OF INSULIN-LIKE GROWTH-FACTORS AND PROGESTINS IN HUMAN ENDOMETRIAL STROMAL CELLS

This study describes the effects of insulin-like growth factors (IGFs), progestins, and IGF binding protein-1 (IGF-BP1) on DNA synthesis in human endometrial stromal cells. Endometrial stromal cells treated with IGF-I or IGF-II or progestins increased their rate of DNA synthesis 3-6-fold. In a time study, IGF-I or IGF-II stimulated DNA synthesis 3-fold in 24 h. An equivalent increase by medroxyprogesterone acetate (MPA) required 48 h. Progestin-stimulated DNA synthesis was inhibited completely by an equimolar concentration of the antiprogesterone RU486. IGF-1-stimulated DNA synthesis was inhibited completely by IGF-BP1. Half-maximal inhibition of IGF-I-stimulated DNA synthesis occurred when IGF-I and IGF-BP1 were at equimolar concentrations. Non-phosphorylated and phosphorylated forms of IGF-BP1 were equipotent inhibitors of IGF-I-stimulated DNA synthesis. IGF-BP1 also inhibited progestin-stimulated DNA synthesis. Half-maximal inhibition of progestin-stimulated DNA synthesis occurred at 100 ng/ml of phosphorylated IGF-BP1. Phosphorylated IGF-BP1 was a 3-4-fold more potent inhibitor of progestin-stimulated DNA synthesis than the nonphosphorylated form. The inhibition by IGF-BP1 of progestin-stimulated DNA synthesis was reversed by an equimolar concentration of IGF-II. This study suggests that progestins regulate an autocrine growth control loop in the endometrium that involves IGFs, IGF receptors, and IGF-BPs.