The inhibitory effect of dienogest, a synthetic steroid, on the growth of human endometrial stromal cells in vitro

Dienogest is a synthetic steroid that has been used as a progestogen in con traceptive pills and is currently being studied for its possible clinical u se in the treatment of endometriosis. In this study, we investigated the di rect effects of dienogest in differentiation and proliferation of human end ometrial stromal cells (ESC) in vitro. After 12 days in the presence of oes tradiol (10(-8) mol/l) plus dienogest (10(-6) mol/l), cultured ESC underwen t morphological differentiation and produced prolactin, a typical marker fo r decidualization. By using Northern blot analysis and radioimmunoassay, it was shown that treatment of ESC with oestradiol (10(-8) mol/l) plus dienog est (10(-9) to 10(-6) mol/l) led to an increase in the levels of prolactin mRNA and prolactin production in a dose-dependent manner. Additionally, RU- 486, a progesterone receptor antagonist, almost completely inhibited dienog est-induced prolactin production. As shown by the thymidine uptake method, there was a dose-dependent inhibition of ESC proliferation with dienogest ( P < 0.01, control versus concentrations >10(-7) mol/l). The significant inh ibition of ESC proliferation by dienogest (10(-7) mol/l) was partially reve rsed by RU-486 (10(-6) mol/l). In summary, dienogest directly acts on endom etrial tissue in progestogenic response, such as decidualization, increased prolactin production and growth retardation. These data imply that dienoge st exerts direct effect in suppressing growth of endometriotic implants.