INSULIN-LIKE GROWTH-FACTOR-I (IGF-I), IGF-I RECEPTORS, AND IGF BINDING-PROTEINS-1-4 IN HUMAN UTERINE TISSUE - TISSUE LOCALIZATION AND IGF-IACTION IN ENDOMETRIAL STROMAL AND MYOMETRIAL SMOOTH-MUSCLE CELLS IN-VITRO

The objective of the present study was to elucidate the presence and c ellular distribution of insulin-like growth factor I (IGF-I), IGF-I re ceptor (IGF-IR), and IGF binding proteins (IGFBPs) in human uterine ti ssue at various reproductive stages, and to determine the effect of IG F-I and its interaction with epidermal growth factor (EGF) and platele t-derived growth factor (PDGF) in endometrial stromal and myometrial s mooth muscle cells in primary culture. Using specific antibodies, immu nohistochemical observations indicated that luminal and glandular epit helial cells were the major sites of immunoreactive IGF-I, IGF-IR, and IGFBPs 1-4, followed by myometrial smooth muscle and endometrial stro mal cells. The immunostaining intensity of IGF-I, IIGF-IR, and IGFBPs in endometrial but not myometrial tissue was cycle-dependent and highe r in the late proliferative and early/mid-secretory periods than in th e late secretory and postmenopausal periods, with little immunostainin g at the early proliferative phase of the menstrual cycle. Stromal and smooth cells in primary cell culture also contained immunoreactive IG F-I, IGF-IR, and IGFBPs. IGF-I at 10-100 ng/ml stimulated H-3-thymidin e incorporation in quiescent stromal and smooth muscle cells with maxi mal effect at 100 ng/ml (p < 0.05). However, in the presence of 2% ser um, which induces half-maximal stimulation, IGF-I (100 ng/ml) further increased the rate of H-3-thymidine incorporation in stromal but not s mooth muscle cells (P < 0.05). The effect of IGF-I was significantly l ower than that induced by EGF (10 ng/ml), PDGF-BB (10 ng/ml) and their combination (P < 0.005), and higher in stromal cells from proliferati ve, than secretory phase of the cycle in the presence of 2% fetal bovi ne serum, but not serum-free condition (p < 0.005). The effect of IGF- I on myometrial smooth muscle cells was significantly higher than that induced by EGF, but lower than that induced by PDGF-BB or by EGF + PD GF-BB, without the cycle specificity seen with stromal cells. EGF, PDG F-BB, and their combination with IGF-I, but not IGF-I alone, stimulate d stromal and smooth muscle cell growth as determined by a cell prolif eration assay. The results indicate that human uterine tissue at vario us reproductive stages contains immunoreactive IGF-I, IGF-IR, and IGFB Ps 1-4. Although IGF-I alone was found to be a weak mitogenic factor f or stromal and smooth muscle cells, by interacting with EGF and PDGF-B B in a cycle-dependent manner it may regulate the growth and different iation of these and other uterine cell types.