Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and EGF and PDGF beta-receptors in human endometrial tissue: localization and in vitro action.

Abstract

Human endometrial tissue and primary stromal cell culture contain immunoreactive epidermal growth factor (EGF), platelet-derived growth factor (PDGF)-AB as well as EGF and PDGF-beta receptors. The immunostaining for EGF, EGF receptor, and PDGF beta-receptor were associated with endometrial luminal and glandular epithelial and stromal cells, whereas only the stromal cells contain immunoreactive PDGF-AB. The immunostaining intensity of EGF, EGF receptor, and PDGF-AB was similar in both phases of the menstrual cycle, whereas, PDGF-beta receptor immunostaining was highest in proliferative phase and considerably reduced, particularly in luminal and glandular epithelial cells in the secretory phase. In addition primary stromal cell cultures express EGF, PDGF-AB, and contain EGF and PDGF-beta receptors, and very low levels of PDGF-alpha receptor. 3H-Thymidine incorporation indicate that after 48 h of incubation in serum-free medium approximately 75-80% of stromal cells are quiescent. Incubation of quiescent stromal cells with 10% fetal bovine serum stimulate 3H-thymidine incorporation in a time-dependent manner reaching maximal after 30-48 h, with a doubling time of 38.2 h. EGF (1.5-15 ng/ml) stimulates 3H-thymidine incorporation by quiescent stromal cells (P less than 0.001). This effect was significantly reduced at concentrations above 15 ng/ml (P less than 0.005). PDGF-AB (3-10 ng/ml) and PDGF-BB (0.5-10 ng/ml) also stimulate 3H-thymidine incorporation in quiescent stromal cells compared to controls (P less than 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 less than 0.002). Addition of PDGF-AB (10 ng/ml) to EGF (15 ng/ml) significantly enhanced the action of EGF or PDGF-AB used individually (P less than 0.001). 17 beta-estradiol or progesterone at 1 microM did not stimulate 3H-thymidine incorporation, although they were stimulatory in combination (P less than 0.001), they did not alter the action of EGF or PDGF when added in combination. These observations provide further evidence that human endometrial tissue contains specific immunoreactive EGF receptors. It also demonstrates the presence of immunoreactive EGF, PDGF-AB, and PDGF-beta receptors in endometrial tissue as well as stromal cells in primary culture. Both EGF and PDGF are mitogenic for endometrial stromal cells, suggesting an autocrine/paracrine role in modulation of endometrial cell growth and differentiation.

Expression of Messenger Ribonucleic Acid and Presence of Immunoreactive Proteins for Epidermal Growth Factor (EGF), Transforming Growth Factor Alpha (TGFα) and EGF/ TGFα Receptors and 1251-EGF Binding Sites in Human Fallopian Tube1

“…Dunn, Jr., Dept of Anatomy and Cell Biology, University of Florida. These two antibodies have been used to localize EGF-R in human uterine tissue [8]. Two additional monoclonal antibodies to EGF-R, clone 29.1 with specificity to the carbohydrate moiety (Sigma Chemical Co., St. Louis, MO) and clone 528, specific to the extracellular binding domain of the EGF-R (a kind gift from Dr. Hideo Masui, Memorial Sloan-Kettering Center, New York, NY) were also used in immunohistochemical studies.…”

“…The expression of growth factors such as epidermal growth factor (EGF), transforming growth factor alpha (TGFa), transforming growth factor beta (TGF3), insulin-like growth factor (IGF), and platelet-derived growth factor (PDGF), and the presence of their receptors in reproductive tissue such as the uterus have been demonstrated [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. In addition, the cycle dependency of the expression of these growth factors and their receptors, as well as modulation by ovarian steroids in ovariectomized animals, has further indicated the involvement of steroid hormones in their regulation [3][4][5][6]10,11,14].…”

Vascular development in endometriosis

“…The precursor cells are recruited by the endothelial cells, presumably by the production of PDGF [101]. Platelet-derived growth factor expression has been described in normal endometrium [102], but has not yet been demonstrated in human endometriosis. However, PDGF levels in the peritoneal fluid were shown to be increased during menstruation [103], most likely as a result of the presence of activated macrophages.…”

Prednisolone treatment reduces endometrial spiral artery development in women with recurrent miscarriage

“…EGF receptors have been more widely studied in terms of tumour angiogenesis as they can be transactivated by several growth factors [32,33]. EGF expression has been described in glandular epithelium, stromal cells and arteries in the endometrium of normal cycling women [34,35] but expression in women with a history of recurrent miscarriage has not been previously described.…”