LHRH might act as a negative autocrine regulator of proliferation of human ovarian cancer

Objective: More than 80% of human ovarian cancers express LHRH and its receptor. The proliferation of human ovarian cancer cell lines is reduced by both LHRH agonists and antagonists. This study was designed to further clarify the possible biological function of this LHRH system. Design: As LHRH agonists and antagonists uniformly reduce proliferation of human ovarian cancer in a dose-dependent way, the effect of low concentrations of authentic LHRH was studied, In addition, longer periods of treatment (up to 9 days) were analyzed, To assess the physiological role of LHRH produced by ovarian cancer cells it was neutralized by adequate concentrations of a specific LHRH antiserum. Methods: Human ovarian cancer cells EFO-21 and EFO-27, which express LHRH and its receptor, were incubated for 1-9 days with increasing concentrations (1 pmol/l to 10 mu mol/l) of authentic LHRH or with concentrations of LHRH antiserum capable of neutralizing at least 1 nmol/l LHRH. Proliferation was assessed by counting cells. Results and conclusions: Authentic LHRH reduced time- and dose-dependently proliferation (by maximally mean +/- S.E.M. 32.7 +/- 4.4%, Newman-Keuls, P < 0.001) of both ovarian cancer cell lines. At very low concentrations (1 pmol/l) a marginal reduction of proliferation or no effect was observed. A mitogenic effect of authentic LHRH was never detected. Treatment of ovarian cancer cell cultures with antiserum to LHRH significantly increased (up to mean +/- S.E.M. 121.0 +/- 2.8% of controls, Newman-Keuls P < 0.001) proliferation of EFO-21 and EFO-27 cells. These findings suggest that LHRH produced by human ovarian cancer cells might act as a negative autocrine regulator of proliferation.