Effects of the levonorgestrel-releasing intrauterine system on proliferation and apoptosis in the endometrium

Takeshi Maruo, T Maruo, J B Laoag-Fernandez, Jovelle B. Laoag‐Fernandez, P Pakarinen, H Murakoshi, Homare Murakoshi, I M Spitz, E Johansson, Elof D.B. Johansson
Human Reproduction · 2001 · vol. 16(10) , pp. 2103–2108 · doi:10.1093/humrep/16.10.2103 · PMID:11574499 · W2171174006
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Levonorgestrel-releasing intrauterine system insertion decreased endometrial proliferation and increased apoptosis in endometrial glands and stroma, associated with altered Fas and Bcl-2 expression.

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Abstract

BACKGROUND: The levonorgestrel-releasing intrauterine system (LNg-IUS) has been shown to be effective in the management of menorrhagia. In order to evaluate the effects of LNg-IUS on endometrial proliferation and apoptosis, proliferating cell nuclear antigen (PCNA) expression, apoptosis, Fas and Bcl-2 protein expression in the endometrium were determined at the early proliferative phase of the menstrual cycle before and 3 months after LNg-IUS insertion. METHODS: PCNA, Fas and Bcl-2 protein expression were analysed using an avidin-biotin immunoperoxidase method. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick-end labelling (TUNEL) method. RESULTS: PCNA, immunolocalized both in the nuclei of endometrial glands and stroma was less abundant 3 months after insertion (P < 0.05). Bcl-2 protein, immunolocalized in the cytoplasm of endometrial glands but not in the stroma, became scanty 3 months after insertion. Fas antigen, immunolocalized only in endometrial glands before insertion, became prominent in both endometrial glands and stroma 3 months after insertion. The apoptosis-positive rate of the nuclei in both endometrial glands and stroma was significantly higher 3 months after insertion relative to that before insertion (P < 0.05). CONCLUSIONS: LNg-IUS resulted in a decrease in endometrial proliferation and an increase in apoptosis in endometrial glands and stroma. The increase in apoptosis associated with increased Fas antigen expression and decreased Bcl-2 protein expression in the endometrium may be one of the underlying molecular mechanisms by which LNg-IUS insertion causes the atrophic change of the endometrium.

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Condition tags

endometriosis

MeSH descriptors

Apoptosis Endometrium Endometrium Levonorgestrel Adult Apoptosis Cell Division Cell Division Drug Delivery Systems Endometriosis Endometriosis Endometrium Endometrium fas Receptor fas Receptor Female Humans Levonorgestrel Levonorgestrel Menorrhagia

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