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

Punyadeera, C., Kamps, R., Defrere, S., Dijcks, F., de Goeij, A., Ederveen, A., Dunselman, G. and Groothuis, P. (2008) Effects of selective oestrogen receptor modulators on proliferation in tissue cultures of pre- and postmenopausal human endometrium. Journal of Steroid Biochemistry and Molecular Biology, 112 1-3: 102-109. doi:10.1016/j.jsbmb.2008.09.002


Author Punyadeera, C.
Kamps, R.
Defrere, S.
Dijcks, F.
de Goeij, A.
Ederveen, A.
Dunselman, G.
Groothuis, P.
Title Effects of selective oestrogen receptor modulators on proliferation in tissue cultures of pre- and postmenopausal human endometrium
Journal name Journal of Steroid Biochemistry and Molecular Biology   Check publisher's open access policy
ISSN 0960-0760
1879-1220
Publication date 2008-11
Sub-type Article (original research)
DOI 10.1016/j.jsbmb.2008.09.002
Volume 112
Issue 1-3
Start page 102
End page 109
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Pergamon
Language eng
Formatted abstract
We characterised the effects of selective oestrogen receptor modulators (SERM) in explant cultures of human endometrium tissue. Endometrium tissueswere cultured for 24 h in Millicell-CM culture inserts in serum-freemedium in the presence of vehicle, 17ß-estradiol (17ß-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, ERß1 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 17ß-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 effectwas 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.
Keyword Human endometrium
Explant culture
Oestradiol
Tamoxifen
Raloxifene
Postmenopausal
Premenopausal
Proliferation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Australian Institute for Bioengineering and Nanotechnology Publications
 
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