PLATELET-DERIVED GROWTH-FACTOR (PDGF), EPIDERMAL GROWTH-FACTOR (EGF),AND EGF AND PDGF BETA-RECEPTORS IN HUMAN ENDOMETRIAL TISSUE - LOCALIZATION AND INVITRO ACTION

Human endometrial tissue and primary stromal cell culture contain immu noreactive epidermal growth factor (EGF), platelet-derived growth fact or (PDGF)-AB as well as EGF and PDGF-beta receptors. The immunostainin g for EGF, EGF receptor, and PDGF beta-receptor were associated with e ndometrial luminal and glandular epithelial and stromal cells, whereas only the stromal cells contain immunoreactive PDGF-AB. The immunostai ning intensity of EGF, EGF receptor, and PDGF-AB was similar in both p hases of the menstrual cycle, whereas, PDGF-beta receptor immunostaini ng was highest in proliferative phase and considerably reduced, partic ularly in luminal and glandular epithelial cells in the secretory phas e. In addition primary stromal cell cultures express EGF, PDGF-AB, and contain EGF and PDGF-beta receptors, and very low levels of PDGF-alph a receptor. H-3-Thymidine incorporation indicate that after 48 h of in cubation in serum-free medium approximately 75-80% of stromal cells ar e quiescent. Incubation of quiescent stromal cells with 10% fetal bovi ne serum stimulate H-3-thymidine incorporation in a time-dependent man ner reaching maximal after 30-48 h, with a doubling time of 38.2 h. EG F (1.5-15 ng/ml) stimulates H-3-thymidine incorporation by quiescent s tromal cells (P < 0.001). This effect was significantly reduced at con centrations above 15 ng/ml (P < 0.005). PDGF-AB (3-10 ng/ml) and PDGF- BB (0.5-10 ng/ml) also stimulate H-3-thymidine incorporation in quiesc ent stromal cells compared to controls (P < 0.005). The action of EGF (15 ng/ml) and PDGF-AB (10 ng/ml) was time dependent, reaching maximal after 36 and 48 h of incubation (P < 0.002). Addition of PDGF-AB (10 ng/ml) to EGF (15 ng/ml) significantly enhanced the action of EGF or P DGF-AB used individually (P < 0.001). 17-beta-estradiol or progesteron e at 1-mu-M did not stimulate H-3-thymidine incorporation, although th ey were stimulatory in combination (P < 0.001), they did not alter the action of EGF or PDGF when added in combination. These observations p rovide further evidence that human endometrial tissue contains specifi c immunoreactive EGF receptors. It also demonstrates the presence of i mmunoreactive EGF, PDGF-AB, and PDGF-beta receptors in endometrial tis sue as well as stromal cells in primary culture. Both EGF and PDGF are mitogenic for endometrial stromal cells, suggesting an autocrine/para crine role in modulation of endometrial cell growth and differentiatio n.