Mifepristone alters expression of endometrial steroid receptors and their cofactors in new users of medroxyprogesterone acetate

Jain, John K.; Li, Aimin; Yang, Wein-Duo; Minoo, Parviz; Felix, Juan C.

doi:10.1016/j.fertnstert.2006.05.076

Cited by 11 publications

(12 citation statements)

References 56 publications

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“…Although the antibody used in the present studies detected both PR-A and PR-B, our results are in overall agreement with the previous findings. Furthermore, increases in ERa and ERb and also PR-A and PR-B were observed in both the glands and stroma after mifepristone treatment of new users of DMPA 1 week after treatment (Jain et al 2007). These results contrast with the present studies in which PR was not detected in the luminal or glandular epithelium after mifepristone treatment.…”

Section: Discussioncontrasting

confidence: 99%

“…Surprisingly, in contrast to the clinical trial, we did not observe any significant differences between mifepristone treatment alone or in conjunction with oestrogen, although it is possible that subtle differences were not detected at the time points selected. Our results indicating an increase in epithelial proliferation are in agreement with previous observations of increased Ki67-positive cells in the endometrium of new DMPA users treated for 1 week with mifepristone (Jain et al 2007). This increase was greater in the glandular epithelium compared with the stroma, similar to the results we obtained with the mouse model.…”

Section: Discussionsupporting

confidence: 93%

“…These results contrast with the present studies in which PR was not detected in the luminal or glandular epithelium after mifepristone treatment. However, our analyses were performed at 48 h after mifepristone treatment, whereas Jain et al (2007) analysed tissue 1 week after treatment. There may also be a difference between mice and women.…”

Section: Discussionmentioning

confidence: 99%

“…Mifepristone has effects on endometrial ER in women (Glasier et al 2002, Jain et al 2007). In the mifepristonetreated mice, there was strong staining for ER in decidual cells in control animals but very little in breaking down tissue (Fig.…”

Section: Oestrogen Receptor Localizationmentioning

confidence: 99%

“…A further reduction in the bleeding days was observed upon mifepristone treatment in conjunction with oestrogen (Weisberg et al 2006). Examination of endometrium following such short-term treatment in the continued presence of progestogen showed increased endometrial proliferation and decreased stromal apoptosis along with increased steroid hormone receptors oestrogen receptor-a (ERa), progesterone receptor (PR-A, PR-B) and the steroid receptor SRC-1 (Jain et al 2006(Jain et al , 2007 in users of DMPA, while in Norplant users, a single dose of mifepristone up-regulated ER and down-regulated PR subtype B in both glands and stroma (Glasier et al 2002), consistent with functional inhibition of progesterone.…”

Section: Introductionmentioning

confidence: 99%

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Stimulation of epithelial repair is a likely mechanism for the action of mifepristone in reducing duration of bleeding in users of progestogen-only contraceptives

et al. 2008

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Many women using progestogen (P)-only contraceptives experience uterine bleeding problems. In clinical trials, a single low dose of mifepristone, given to Implanon users at the beginning of a bleeding episode reduced the number of bleeding days by w50% compared with controls. In this study, a single dose of mifepristone was administered to etonogestrel (ENG)-exposed pseudo-pregnant mice, 5 days after artificial decidualization was induced when the endometrium showed signs of bleeding. Control mice received vehicle alone. Mice were culled 12-, 18-, 24-and 48-h post-treatment. In the continued presence of ENG, a single dose of mifepristone stimulated tissue breakdown followed by very rapid repair: most treated tissues were fully restored to the pre-decidualized state by 48 h post-treatment. During repair, proliferating cells (Ki67 immunostained) were localized to a band of cells around the basal area in breaking down tissues and to the repairing luminal epithelium and glands. Progesterone receptor-positive cells were largely localized to the basal area of the breaking down tissue in treated mice compared with decidual cells in controls. Oestrogen receptor-positive cells were observed in the repairing luminal epithelium and glands compared with the decidua and the basal region in control tissues. It is concluded that mifepristone treatment stimulates rapid restoration of luminal epithelial integrity: such action may be a key event in reducing the number of bleeding days observed in women using Implanon who were treated with a single dose of mifepristone.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Oestrogen Receptor Localizationmentioning

confidence: 99%