PMID- 17094978 OWN - NLM STAT- MEDLINE DCOM- 20070125 LR - 20131121 IS - 1556-5653 (Electronic) IS - 0015-0282 (Linking) VI - 87 IP - 1 DP - 2007 Jan TI - Mifepristone alters expression of endometrial steroid receptors and their cofactors in new users of medroxyprogesterone acetate. PG - 8-23 AB - OBJECTIVE: To evaluate the effect of mifepristone on the expression of endometrial steroid receptors and their co-factors in depot medroxyprogesterone acetate (DMPA) users. DESIGN: A prospective, randomized, placebo-controlled trial. SETTING: Reproductive research center. PATIENT(S): Fifty healthy women with regular menstrual cycle. INTERVENTION(S): One hundred fifty milligrams of DMPA were given every 3 months. Two pills (25 mg each) of placebo or mifepristone were administered every 14 days during the DMPA therapy. Four endometrial biopsy specimens were obtained from each patient. MAIN OUTCOME MEASURE(S): The expression of estrogen receptor subtypes alpha and beta (ERalpha and ERbeta), progesterone receptors A and B (PRAB and PRB), and androgen receptor messenger RNA and protein was detected by real-time polymerase chain reaction and immunohistochemistry, respectively. Steroid receptor coactivator 1 (SRC-1), silencing mediator for retinoid and thyroid-hormone receptors, and cell proliferation were evaluated by immunohistochemistry. RESULT(S): The expression of endometrial ERalpha, PRAB, PRB, and SRC-1 was increased significantly after 1 week of mifepristone, but the increase was no longer seen after 10 weeks. A positive correlation between endometrial ERalpha, PRAB, PRB, and SRC-1 production and proliferation was demonstrated. CONCLUSION(S): Short-term exposure of mifepristone in new starters of DMPA increases the expression of endometrial ERalpha, PRAB, PRB, and SRC-1 and promotes cell proliferation. Prolonged exposure to mifepristone does not alter the suppression of these receptors that are caused by DMPA and continues to result in endometrial atrophy. FAU - Jain, John K AU - Jain JK AD - Department of Obstetrics and Gynecology, The Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. jjain@usc.edu FAU - Li, Aimin AU - Li A FAU - Yang, Wangrong AU - Yang W FAU - Minoo, Parviz AU - Minoo P FAU - Felix, Juan C AU - Felix JC LA - eng GR - 1 R03 HDO 47322/PHS HHS/United States GR - R0-1 HD 43189/HD/NICHD NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural DEP - 20061107 PL - United States TA - Fertil Steril JT - Fertility and sterility JID - 0372772 RN - 0 (Contraceptives, Oral, Synthetic) RN - 0 (Drug Combinations) RN - 0 (Protein Isoforms) RN - 0 (Receptors, Steroid) RN - 320T6RNW1F (Mifepristone) RN - C2QI4IOI2G (Medroxyprogesterone Acetate) SB - IM MH - Contraceptives, Oral, Synthetic/administration & dosage MH - Double-Blind Method MH - Drug Combinations MH - Endometrium/drug effects/*metabolism MH - Female MH - Gene Expression/drug effects MH - Humans MH - Medroxyprogesterone Acetate/*administration & dosage MH - Mifepristone/*administration & dosage MH - Placebo Effect MH - Protein Isoforms/metabolism MH - Receptors, Steroid/*metabolism EDAT- 2006/11/11 09:00 MHDA- 2007/01/26 09:00 CRDT- 2006/11/11 09:00 PHST- 2006/02/15 00:00 [received] PHST- 2006/05/22 00:00 [revised] PHST- 2006/05/22 00:00 [accepted] PHST- 2006/11/11 09:00 [pubmed] PHST- 2007/01/26 09:00 [medline] PHST- 2006/11/11 09:00 [entrez] AID - S0015-0282(06)03171-2 [pii] AID - 10.1016/j.fertnstert.2006.05.076 [doi] PST - ppublish SO - Fertil Steril. 2007 Jan;87(1):8-23. doi: 10.1016/j.fertnstert.2006.05.076. Epub 2006 Nov 7.