Concurrent estrogen action was essential for maximal progestin effect in oral contraceptives
Concurrent estrogen action enhances the progestin-induced growth inhibition of ovarian endometrioma epithelial cells via up-regulation of progestin receptor B expression in oral contraceptives.
Yukiko Bono, M.D., Ph.D., Satoru Kyo, M.D., Ph.D., Tohru Kiyono, M.D., Ph.D., Yasunari Mizumoto, M.D., Ph.D., Mitsuhiro Nakamura, M.D., Ph.D., Yoshiko Maida, M.D., Ph.D., Masahiro Takakura, M.D., Ph.D., Hiroshi Fujiwara, M.D., Ph.D.
Volume 101, Issue 5, Pages 1337–1343
To investigate the impact of estrogen contained in oral contraceptives (OCs) on the action of progestin on ovarian endometrioma epithelial cells.
Experimental in vitro study and immunohistochemical analysis.
Patients who underwent surgery due to ovarian endometrioma.
Main Outcome Measure(s):
Telomerase-immortalized epithelial cells derived from ovarian endometrioma were treated with norethindorone (NET; 80 nmol/L) or levonorgestrel (LNG; 20 nmol/L) with or without 17β-ethynylestradiol (EE; 0.6 nmol/L) for 96 hours, and the cell growth was monitored. Estrogen receptor (ER) α, progesterone receptor (PR) A, and PRB expressions in clinical samples of ovarian endometrioma epithelial cells were analyzed with the use of immunohistochemistry.
NET or LNG effectively suppressed cell growth, and addition of EE significantly enhanced the growth suppression. This EE-mediated enhancement of cell growth suppression was observed only in cells that expressed ERα and therefore was ERα dependent. Western blot analysis revealed that expression of PRB was significantly induced by the addition of EE. Immunohistochemical analysis confirmed that ERα expression and PRB expression are significantly correlated, indicating that progestin-sensitive cells with PRB expression are predisposed to react with estrogen stimulation.
These findings suggest that EE contained in OCs plays a supportive role in progestin-induced growth inhibition of ovarian endometrioma epithelial cells. In the absence of estrogen priming, concurrent estrogen action was essential for rapid induction of PR to achieve maximal progestin effect.