A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Effects of ospemifene, a novel selective estrogen-receptor modulator, on human breast tissue ex vivo
Tekijät: Eigeliene N, Kangas L, Hellmer C, Kauko T, Erkkola R, Härkönen P
Kustantaja: LIPPINCOTT WILLIAMS & WILKINS
Julkaisuvuosi: 2016
Journal: Menopause
Tietokannassa oleva lehden nimi: MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
Lehden akronyymi: MENOPAUSE
Vuosikerta: 23
Numero: 7
Aloitussivu: 719
Lopetussivu: 730
Sivujen määrä: 12
ISSN: 1072-3714
DOI: https://doi.org/10.1097/GME.0000000000000624
Tiivistelmä
Objective: Ospemifene (Osp) is a novel selective estrogen-receptor modulator (SERM) accepted for the treatment of dyspareunia, a symptom of postmenopausal vulvovaginal atrophy. We aimed to analyze the effects of Osp on human breast tissue (HBT), in comparison with the clinically established SERMs raloxifene (Ral) and tamoxifen (Tam), using ex vivo explant cultures.Methods: HBT samples were obtained from postmenopausal women undergoing mammoplasty and cultured with or without Osp, Ral, Tam, or 17 beta-estradiol (E-2) for 7 and 14 days, and studied for morphology, proliferation, and apoptosis. The expression of epithelial markers, the estrogen-receptor alpha (ER alpha), the androgen receptor (AR), TFF1, and apolipoprotein D was evaluated using immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. The PvuII polymorphism of ERS1 was determined.Results: Osp, similar to Ral and Tam, decreased the number of proliferating cells in a concentration-dependent manner (at 100 nM, P<0.01) and strongly opposed 10 nM E-2-stimulated proliferation (P<0.001). Corresponding effects were observed in the proportions of cells expressing ER alpha and TFF1 (P<0.001). At 14 days apoptosis was increased by 100nM SERMs (P<0.01), but, notably, decreased by 1nM Osp and Ral at day 7 (P<0.05). The SERMs exerted ER-agonist effects on AR-positive cell populations at 1 nM (P<0.05), but not at 100nM concentrations. The effects on proliferation and ER alpha expressing cell numbers were associated with the ERS1 PvuII genotype.Conclusions: In summary, Osp inhibited proliferation and opposed E-2 stimulation in normal HBT in an efficacious, but less potent way than Ral and Tam. The ESR1 PvuII polymorphisms may influence the responsiveness of HBT to E-2 and SERMs.
Objective: Ospemifene (Osp) is a novel selective estrogen-receptor modulator (SERM) accepted for the treatment of dyspareunia, a symptom of postmenopausal vulvovaginal atrophy. We aimed to analyze the effects of Osp on human breast tissue (HBT), in comparison with the clinically established SERMs raloxifene (Ral) and tamoxifen (Tam), using ex vivo explant cultures.Methods: HBT samples were obtained from postmenopausal women undergoing mammoplasty and cultured with or without Osp, Ral, Tam, or 17 beta-estradiol (E-2) for 7 and 14 days, and studied for morphology, proliferation, and apoptosis. The expression of epithelial markers, the estrogen-receptor alpha (ER alpha), the androgen receptor (AR), TFF1, and apolipoprotein D was evaluated using immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. The PvuII polymorphism of ERS1 was determined.Results: Osp, similar to Ral and Tam, decreased the number of proliferating cells in a concentration-dependent manner (at 100 nM, P<0.01) and strongly opposed 10 nM E-2-stimulated proliferation (P<0.001). Corresponding effects were observed in the proportions of cells expressing ER alpha and TFF1 (P<0.001). At 14 days apoptosis was increased by 100nM SERMs (P<0.01), but, notably, decreased by 1nM Osp and Ral at day 7 (P<0.05). The SERMs exerted ER-agonist effects on AR-positive cell populations at 1 nM (P<0.05), but not at 100nM concentrations. The effects on proliferation and ER alpha expressing cell numbers were associated with the ERS1 PvuII genotype.Conclusions: In summary, Osp inhibited proliferation and opposed E-2 stimulation in normal HBT in an efficacious, but less potent way than Ral and Tam. The ESR1 PvuII polymorphisms may influence the responsiveness of HBT to E-2 and SERMs.
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