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Progesterone and synthetic progestin, dienogest, induce apoptosis of human primary cultures of adenomyotic stromal cells.

Eur J Obstet Gynecol Reprod Biol. 2014 Aug;179:170-4. doi: 10.1016/j.ejogrb.2014.05.031. Epub 2014 Jun 2.

Yamanaka A1, Kimura F2, Kishi Y3, Takahashi K4, Suginami H3, Shimizu Y5, Murakami T2.

Eur J Obstet Gynecol Reprod Biol
AbstractOBJECTIVES: To investigate the direct effects of progesterone receptor (PR) agonists on proliferation and apoptosis of human adenomyotic cells.STUDY DESIGN: 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.Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
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PMID:24953822 |

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