OBJECTIVE: This study was designed to investigate the ovarian carcinogenesis process related to various steroids and peptide hormones. METHODS: We tested the proliferative effect of estradiol (E), dihydrotestosterone (DHT), progesterone (P), lutenizing hormone (LH), follicular stimulating hormone (FSH) and epidermal growth factor (EGF) on each ovarian surface epithelial cell line - normal human ovarian surface epithelial cells (HOSE) obtained by primary culture through the surgical specimen, an immortalized rat ovarian surface epithelial cell line (ROSE), and the human ovarian epithelial cancer cell line (SK-OV-3). Cells were grown in the presence of various concentrations of the different steroids (1, 5, 10, 50, 100 nM), LH and FSH (5, 10, 50, 100 mIU/ml), or EGF (1, 3, 5, 10, 30 ng/ml) for 5-7 days. Cell proliferation was determined by a colorimetric assay (MTT). RESULTS: E or DHT had a negligible effect on HOSE, ROSE, or SK-OV-3 cell proliferation. P had a significant inhibitory effect of approximately 30 % on HOSE proliferation at all concentrations tested (p<0.05), but there was no effect of P on either ROSE or SK-OV-3 cells. LH or FSH had no significant effect on cell growth in any of the cell lines tested. EGF had no effect on HOSE or ROSE, but significantly stimulated cell growth in SK-OV-3 cells by approximately 20% at 3 and 10 ng/ml (p<0.05). CONCLUSION: We conclude that differences observed in the responsiveness of normal versus immortalized or transformed OSE cells to these agents suggest that cancer cell has escaped from the physiologic hormonal control during the process of carcinogenesis. In particular, the ability of progesterone to inhibit the proliferation of normal but not the immortalized or transformed OSE cells indicates that the latter cell lines have lost their responsiveness to growth inhibition by progesterone. This observation suggests that progesterone may play a protective role in the transformation of the ovarian surface epithelium.
Animals ; Carcinogenesis ; Cell Line ; Cell Proliferation ; Dihydrotestosterone ; Epidermal Growth Factor* ; Epithelial Cells* ; Epithelium ; Estradiol ; Gonadotropins* ; Humans ; Peptide Hormones ; Progesterone ; Rats ; Steroids* ; United Nations