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Hum. Reprod. Advance Access published online on December 11, 2007
Human Reproduction, doi:10.1093/humrep/dem366
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Difference in signalling between various hormone therapies in endometrium, myometrium and upper part of the vagina

Payman Hanifi-Moghaddam1, Bianca Boers-Sijmons1, Anet H.A. Klaassens1, F. Heidy van Wijk1, Wilfred F. Van Ijcken2, Peter Van der Spek3, Herman A.M. Verheul4, Helenius J. Kloosterboer4, Curt W. Burger1 and Leen J. Blok1,5

1 Department of Obstetrics and Gynaecology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands 2 Department of Celbiology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands 3 Department of Bioinformatics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands 4 N.V. Organon, 5342 PX Oss, The Netherlands

5 Correspondence address. Tel: +31-10-7044111; E-mail: l.blok{at}erasmusmc.nl

BACKGROUND: Combined hormone treatments in post-menopausal women have different clinical responses on uterus and vagina; therefore, we investigated differences in steroid signalling between various hormone therapies in these tissues.

METHODS: A total of 30 post-menopausal women scheduled for hysterectomy were distributed into four subgroups: control-group (n = 9), Tibolone-group (n = 8); estradiol (E2)-group (n = 7); E2 + medroxyprogesterone acetate (MPA)-group (n = 6). Medication was administered orally every day for 21 days prior to removal of uterus and upper part of the vagina. Tissue RNA was isolated, and gene expression profiles were generated using GeneChip technology and analysed by cluster analysis and significance analysis of microarrays. Apoptosis and cell proliferation assays, as well as immunohistochemistry for hormone receptors were performed.

RESULTS: 21-days of treatment with E2, E2 + MPA or tibolone imposes clear differential gene expression profiles on endometrium and myometrium. Treatment with E2 only results in the most pronounced effect on gene expression (up to 1493 genes differentially expressed), proliferation and apoptosis. Tibolone, potentially metabolized to both estrogenic and progestagenic metabolites, shows some resemblance to E2 signalling in the endometrium and, in contrast, shows significant resemblance to E2 + MPA signalling in the myometrium. In the vagina the situation is entirely different; all three hormonal treatments result in regulation of a small number (4–73) of genes, in comparison to signalling in endometrium and myometrium.

CONCLUSION: Endometrium and myometrium differentially respond to the hormone therapies and use completely different sets of genes to regulate similar biological processes, while in this experiment the upper part of the vagina is hardly hormone responsive.

Key words: endometrium/myometrium/vagina/estradiol tibolone/gene expression

Submitted on August 27, 2007; resubmitted on October 9, 2007; accepted on October 18, 2007.


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