A NOVEL ACTION OF EPIDERMAL GROWTH-FACTOR IN RAT GRANULOSA-CELLS - ITS POTENTIATION OF GONADOTROPIN ACTION

It is well known that epidermal growth factor (EGF) induces down-regul ation of LH receptors and desensitization to gonadotrophin stimulation in gonadal cells, including granulosa cells. In a previous study we s howed that EGF receptor levels in rat granulosa cells were increased u p to fourfold after 96 h of culture with human GH in the presence of F SH, and the present study has evaluated the action of EGF on these cel ls. The induced EGF receptors were identical in size to the pre-existi ng receptors as assessed by affinity labelling with I-125-EGF. After 4 8 h in culture, various amounts of EGF (0.5-10 ng) were added and the cells were cultured for a further 48 h. The addition of EGF caused dow n-regulation of LH receptors in cells expressing high levels of EGF re ceptors. However, this down-regulation was less than that in control c ells. After the cells were washed, cAMP synthesis in response to human chorionic gonadotrophin (hCG) increased by two to three times the con trol value and this increase was closely correlated with an increase i n EGF receptor content. However, stimulation with cholera toxin or for skolin showed no such augmentation, indicating that it may not be due to quantitative alterations in G proteins and their effector systems. Induction of EGF potentiation required long-term exposure to EGF, for at least more than 24 h. In addition, progesterone synthesis was sensi tive to stimulation with lower doses of hCG. These findings indicate t hat the activation of hGH-induced EGF receptors may potentiate gonadot rophin action in granulosa cells.