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

Citation
H. Okada et al., The inhibitory effect of dienogest, a synthetic steroid, on the growth of human endometrial stromal cells in vitro, MOL HUM REP, 7(4), 2001, pp. 341-347
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR HUMAN REPRODUCTION
ISSN journal
1360-9947 → ACNP
Volume
7
Issue
4
Year of publication
2001
Pages
341 - 347
Database
ISI
SICI code
1360-9947(200104)7:4<341:TIEODA>2.0.ZU;2-S
Abstract
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.