Drospirenone induces decidualization in human eutopic endometrial stromal cells and reduces DNA synthesis of human endometriotic stromal cells.
OBJECTIVE
To investigate the in vitro effect of drospirenone on human eutopic endometrial (EuSC) and ectopic endometriotic stromal cells (EcSC).


METHODS
Comparative and laboratory study. The experimental procedures were approved by the Institutional Review Board of the University of Tokyo (registration no. 0324-4).


METHODS
University research laboratory.


METHODS
Eight patients undergoing hysterectomy for benign gynecologic disease and 19 patients undergoing cystectomy or adnectomy for endometriosis.


METHODS
EuSC and EcSC were treated with drospirenone.


METHODS
For the analysis of decidualization of EuSC, cells were observed using microscopy, and the production of PRL was measured using enzyme immunoassay. For the analysis of DNA synthesis of EcSC, 5-bromo-2'-deoxyuridine incorporation was measured by ELISA. Cells in apoptosis were detected and measured by flow cytometry.


RESULTS
Drospirenone induced decidualization in EuSC, and the induction was negated by RU486. Drospirenone reduced DNA synthesis on EcSC, and this reduction was negated by RU486 or P receptor silencing, but not by aldosterone or mineralocorticoid receptor silencing. Drospirenone did not cause EcSC to undergo apoptosis.


CONCLUSIONS
Our study demonstrates the direct effects of drospirenone: decidualization of EuSC and reduced DNA synthesis of EcSC, but it does not cause EsSC apoptosis.
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.
Mariko
M
Miyashita
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan. Electronic address: kawotan-tky@umin.ac.jp.
Kaori
K
Koga
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.
Gentaro
G
Izumi
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.
Tomoko
T
Makabe
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.
Akiko
A
Hasegawa
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.
Yasushi
Y
Hirota
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.
Tetsuya
T
Hirata
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.
Miyuki
M
Harada
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.
Tomoyuki
T
Fujii
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.
Yutaka
Y
Osuga
D000328:Adult; D000736:Androstenes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects* / Q000502:physiology; D003656:Decidua / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
D000736:Androstenes; C035144:drospirenone
Drospirenone; decidualization; endometriosis; endometrium; oral contraceptive(s)