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Progestagenic Effects of Tibolone are Target Gene—Specific In Human Endometrial Cells

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The Journal of the Society for Gynecologic Investigation: JSGI Aims and scope Submit manuscript

Abstract

Objectives

Tibolone (Tib) exhibits progestagenic activities in addition to its tissue-specific estrogenic activities. The purpose of the current study was to determine the progestagenic actions of Tib and its metabolites using target genes known to be regulated by progestins in human endometrial glandular and stromal cells.

Methods

Human endometrial glandular and stromal cells were isolated from endometrial tissue fragments and separately incubated with Tib and its metabolites. Real-time polymerase chain reaction (PCR) was used to determine the mRNA content of 17βhydroxy steroid dehydrogenase (17βHSD, type 2) and sulfotransferase (SULT1E1) in endometrial glandular cells, and prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP1) in endometrial stromal cells.

Results

In glandular cells, Tib and Δ4-tibolone (Δ4Tib) significantly increased the content of 17βHSD and SULT1E1 mRNA. In stromal cells, Tib and Δ4Tib increased PRL mRNA (∼ 30% of the capacity compared to progesterone) and had little effect on IGFBP1 mRNA. Anti-progestin, RU486, reversed the induction of SULT1E1 and PRL by progesterone or Tib. Also, the two 3 hydroxyl tobolone metabolites, especially 3βOHTib, showed some progestagenic effects.

Conclusions

The data showed that Tib and Δ4Tib exhibited clear progestagenic effects in endometrial glandular cells by inducing 17βHSD and SULT1E1, while in stromal cells the response was weaker in the induction of PRL and had little effect on IGFBP1. In addition, the 3βOHTib metabolite expressed progestagenic activity. These disparate effects in two types of cells may be beneficial for maintaining endometrial cells in a quiescent state.

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Authors and Affiliations

  1. Department of Obstetrics/Gynecology and Reproductive Medicine, SUNY-Stony Brook, HSC T9-83, Stony Brook, New York, 11794, USA

    Wei Zhang MD, James Mazella BS, Helenius J. Kloosterboer PhD & Linda Tseng PhD

  2. N.V. Organon, Oss, the Netherlands

    Wei Zhang MD, James Mazella BS, Helenius J. Kloosterboer PhD & Linda Tseng PhD

Authors
  1. Wei Zhang MD
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  2. James Mazella BS
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  3. Helenius J. Kloosterboer PhD
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  4. Linda Tseng PhD
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Corresponding author

Correspondence to Linda Tseng PhD.

Additional information

Supported by grants NIH HD 19247-16 and Organon 31480.

The authors thank the clinicians in the Department of Obstetrics/Gynecology and Reproductive Medicine and the Department of Pathology and SUNY-Stony Brook for providing us with viable endometrial specimens.

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Zhang, W., Mazella, J., Kloosterboer, H.J. et al. Progestagenic Effects of Tibolone are Target Gene—Specific In Human Endometrial Cells. Reprod. Sci. 13, 459–465 (2006). https://doi.org/10.1016/j.jsgi.2006.05.004

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  • DOI: https://doi.org/10.1016/j.jsgi.2006.05.004

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