title: Progesterone and synthetic progestin, dienogest, induce apoptosis of human primary cultures of adenomyotic stromal cells.
abstract: OBJECTIVE
  To investigate the direct effects of progesterone receptor (PR) agonists on proliferation and apoptosis of human adenomyotic cells.
  
  
  METHODS
  Human primary cultures of adenomyotic stromal cells (ASCs) from 24 patients with adenomyosis were co-treated with estradiol (E2) plus the PR agonists, endogenous progesterone (P) or the synthetic progestin dienogest (DNG), which is used to treat endometriosis. In ASCs, anti-proliferative effects and induction of apoptosis were evaluated in the presence or absence of P (10(-8)-10(-6)M) or DNG (10(-8)-10(-6)M) in culture medium containing E2. Cellular proliferation was analyzed with bromodeoxyuridine incorporation and flow cytometry. Apoptosis was detected with annexin V/7-amino-actinomycin D (7-AAD) staining with flow cytometry and cellular caspase 3/7 activity.
  
  
  RESULTS
  P and DNG significantly decreased the proportion of cells in the S phase. In addition, both P and DNG increased apoptosis as measured by annexin V-positive/7-AAD -negative cells and caspase 3/7 activity.
  
  
  CONCLUSIONS
  Both endogenous P and synthetic progestin directly inhibited cellular proliferation and induced apoptosis in human ASCs. These pharmacological features of progestational compounds provide insight into the therapeutic strategy for the treatment of adenomyosis.
authors: Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta Tuskinowa-cho, Otsu, Shiga 520-2192, Japan. Electronic address: ykiyoshi@belle.shiga-med.ac.jp.
authors: Akiyoshi
authors: A
authors: Yamanaka
authors: Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta Tuskinowa-cho, Otsu, Shiga 520-2192, Japan.
authors: Fuminori
authors: F
authors: Kimura
authors: Department of Obstetrics and Gynecology, Takanohara Central Hospital, Nara, Japan.
authors: Yohei
authors: Y
authors: Kishi
authors: Department of Community Perinatal Medicine, Shiga University of Medical Science, Otsu, Japan.
authors: Kentaro
authors: K
authors: Takahashi
authors: Department of Obstetrics and Gynecology, Takanohara Central Hospital, Nara, Japan.
authors: Hiroshi
authors: H
authors: Suginami
authors: Development Research, Mochida Pharmaceutical Co., Ltd., Gotemba, Japan.
authors: Yutaka
authors: Y
authors: Shimizu
authors: Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta Tuskinowa-cho, Otsu, Shiga 520-2192, Japan.
authors: Takashi
authors: T
authors: Murakami
mesh_terms: D062788:Adenomyosis / Q000473:pathology*; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D017154:Stromal Cells / Q000187:drug effects* / Q000473:pathology
chemical_list: C023635:dienogest; D011374:Progesterone; D004958:Estradiol; D009277:Nandrolone
keywords: Adenomyosis; Adenomyotic stromal cells; Apoptosis; Dienogest; Progesterone