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-I-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.
Frost
R A
RA
Graduate Program in Molecular and Cellular Biology, School of Medicine, State University of New York, Stony Brook 11794.
Mazella
J
J
Tseng
L
L
D000328:Adult; D002352:Carrier Proteins / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D018970:Insulin-Like Growth Factor Binding Protein 1; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D013002:Somatomedins / Q000378:metabolism* / Q000494:pharmacology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D008934:Mitogens; D013002:Somatomedins; D004247:DNA; D017258:Medroxyprogesterone Acetate