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Departments of Reproduction and Development,
¹ Obstetrics and Gynecology,
² Center for Biomics,
³ Bioinformatics, Erasmus University Medical Center, 3000 DR Rotterdam, The Netherlands,
⁴ OmniViz, Inc., Maynard, Massachusetts, USA and
⁵ Research and Development Laboratories, N V Organon, 5340 BH Oss, The Netherlands

(Requests for offprints should be addressed to P Hanifi-Moghaddam; Email: p.hanifi_moghaddam{at}erasmusmc.nl)

Tibolone, a steroidogenic compound with both estrogenic and progestagenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. We have evaluated whether the effect of tibolone on a human endometrial cell line is similar to, or comparable with, the effect of estradiol (E₂), medroxyprogesterone acetate (MPA) or E₂ + MPA treatment. Using stable transfection techniques, the estrogen receptor (ER) expressing human endometrial cancer cell line, ECC1, was altered to also express both progesterone receptors (PRs). These cells were then used to assess growth regulation and expression profiling (Affymetrix U133plus2) under the influence of E₂ (1 nM), MPA (1 nM), E₂ + MPA or tibolone (100 nM). Growth assessment and comparison of profiles indicate that tibolone behaves predominantly like MPA. Furthermore, regulation of prereplication complex genes, such as the minichromosome maintenance genes, could be involved in the observed strong inhibition of growth by tibolone as well as MPA. In addition, in total, 15 genes were found to be specific for tibolone treatment. These genes were predominantly involved in regulation of the cell cycle and differentiation.

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				S. C. J. P. Gielen, L. A. M. Santegoets, L. C. M. Kuhne, W. F. J. Van IJcken, B. Boers-Sijmons, P. Hanifi-Moghaddam, T. J. M. Helmerhorst, L. J. Blok, and C. W. Burger Genomic and Nongenomic Effects of Estrogen Signaling in Human Endometrial Cells: Involvement of the Growth Factor Receptor Signaling Downstream AKT Pathway Reproductive Sciences, October 1, 2007; 14(7): 646 - 654. [Abstract] [PDF]