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

Hidetaka Okada, H Okada, T Nakajima, T Yoshimura, K Yasuda, H Kanzaki
Molecular human reproduction · 2001 · vol. 7(4) , pp. 341–347 · doi:10.1093/molehr/7.4.341 · PMID:11279296 · W2166280534
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Dienogest induced morphological differentiation and increased prolactin production in human endometrial stromal cells, while inhibiting their proliferation in a dose-dependent manner.

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Abstract

Dienogest is a synthetic steroid that has been used as a progestogen in contraceptive pills and is currently being studied for its possible clinical use in the treatment of endometriosis. In this study, we investigated the direct effects of dienogest in differentiation and proliferation of human endometrial stromal cells (ESC) in vitro. After 12 days in the presence of oestradiol (10(-8) mol/l) plus dienogest (10(-6) mol/l), cultured ESC underwent morphological differentiation and produced prolactin, a typical marker for decidualization. By using Northern blot analysis and radioimmunoassay, it was shown that treatment of ESC with oestradiol (10(-8) mol/l) plus dienogest (10(-9) to10(-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 dienogest-induced prolactin production. As shown by the thymidine uptake method, there was a dose-dependent inhibition of ESC proliferation with dienogest (P 10(-7) mol/l). The significant inhibition of ESC proliferation by dienogest (10(-7) mol/l) was partially reversed by RU-486 (10(-6) mol/l). In summary, dienogest directly acts on endometrial tissue in progestogenic response, such as decidualization, increased prolactin production and growth retardation. These data imply that dienogest exerts direct effect in suppressing growth of endometriotic implants.

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Condition tags

endometriosis

MeSH descriptors

Contraceptives, Oral Endometrium Nandrolone Cell Division Cell Division Cells, Cultured Contraceptives, Oral Contraceptives, Oral Contraceptives, Oral Endometrium Endometrium Estradiol Estradiol Female Hormone Antagonists Hormone Antagonists Humans Mifepristone Mifepristone Molecular Structure

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