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  • Effects of selective oestrogen receptor modulators on proliferation in tissue cultures of pre- and postmenopausal human endometrium

    Author(s)
    Punyadeera, C
    Kamps, R
    Defrere, S
    Dijcks, F
    de Goeij, A
    Ederveen, A
    Dunselman, G
    Groothuis, P
    Griffith University Author(s)
    Punyadeera, Chamindie
    Year published
    2008
    Metadata
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    Abstract
    We characterised the effects of selective oestrogen receptor modulators (SERM) in explant cultures of human endometrium tissue. Endometrium tissues were cultured for 24 h in Millicell-CM culture inserts in serum-free medium in the presence of vehicle, 17β-estradiol (17β-E2, 1 nM), oestrogen receptor (ER) antagonist ICI 164.384 (40 nM), and 4-OH-tamoxifen (40 nM), raloxifene (4 nM), lasofoxifene (4 nM) and acolbifene (4 nM). Protein expression of ERα, ERβ1 and Ki-67 were evaluated by immunohistochemistry (IHC). The proliferative fraction was assessed by counting the number of Ki-67 positive cells. Nuclear staining of ER( and ...
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    We characterised the effects of selective oestrogen receptor modulators (SERM) in explant cultures of human endometrium tissue. Endometrium tissues were cultured for 24 h in Millicell-CM culture inserts in serum-free medium in the presence of vehicle, 17β-estradiol (17β-E2, 1 nM), oestrogen receptor (ER) antagonist ICI 164.384 (40 nM), and 4-OH-tamoxifen (40 nM), raloxifene (4 nM), lasofoxifene (4 nM) and acolbifene (4 nM). Protein expression of ERα, ERβ1 and Ki-67 were evaluated by immunohistochemistry (IHC). The proliferative fraction was assessed by counting the number of Ki-67 positive cells. Nuclear staining of ER( and ER(1 was observed in the glandular epithelium and stroma of pre- and postmenopausal endometrium. ER(1 protein was also localized in the endothelial cells of blood vessels. Treating premenopausal endometrium tissue with 17β-E2 increased the fraction of Ki-67 positive cells (p < 0.001) by 55% in glands compared to the control. Raloxifene (4 nM) increased (p < 0.05) the Ki-67 positive fraction. All other SERMS did not affect proliferation in this model. Treating postmenopausal endometrium with 17(-E2 increased (p < 0.001) the fraction of Ki-67 positive cells by 250% in glands compared to the control. A similar effect was also seen for 4-OH-tamoxifen, whereas the rest of SERMs did not stimulate proliferation. We demonstrated that oestradiol increases the fraction of proliferating cells in short term explant cultures of postmenopausal endometrium. In addition, we were able to reveal the agonistic properties of 4-OH-tamoxifen and confirm that raloxifene and next-generation SERMs acolbifene and lasofoxifene were neutral on the human postmenopausal endometrium. © 2008 Elsevier Ltd. All rights reserved.
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    Journal Title
    The Journal of Steroid Biochemistry and Molecular Biology
    Volume
    112
    Issue
    1-3
    DOI
    https://doi.org/10.1016/j.jsbmb.2008.09.002
    Subject
    Science & Technology
    Life Sciences & Biomedicine
    Biochemistry & Molecular Biology
    Endocrinology & Metabolism
    Human endometrium
    Publication URI
    http://hdl.handle.net/10072/412201
    Collection
    • Journal articles

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