Expression of Apoptosis-Related Proteins in Adenomyotic Uteri Treated with Danazol and GnRH Agonists

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Adenomyotic endometrium shows increased ER and bcl-2 expression, with danazol and GnRH agonists both inducing apoptosis, though danazol treatment leads to postapoptotic necrosis rather than typical apoptosis.

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Abstract

The biologic properties of adenomyosis and the effects of therapeutic agents on adenomyosis were evaluated with immunohistochemistry, terminal deoxy-nucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method, transmission electron microscopy, and analysis of genomic abnormality. In the adenomyotic endometrium, estrogen receptor (ER) expression was more intense than in the eutopic endometrium during the secretory phase, and bcl-2 was constantly expressed throughout the menstrual cycle. The expression of ER and bcl-2 was weaker in the adenomyotic endometrium treated with danazol than in that treated with gonadotro-pin-releasing hormone agonist (GnRHa), whereas bcl-2 phosphorylated on serine-87 was more intensely expressed in danazol-treated adenomyotic endometrium than in the GnRHa-treated one. The number of TUNEL-positive cells increased in the adenomyotic endometrium treated with danazol or GnRHa. Ultrastructurally, most of the adenomyotic endometrial cells treated with danazol underwent postapoptotic necrosis and formed a cluster of dead cells. In contrast, cells treated with GnRHa underwent typical apoptosis and were sparsely distributed in the adenomyotic endometrium. Analysis of several cancer-related genes showed no microsatellite instability or loss of heterozygosity in adenomyotic tissues. Therefore, we conclude that the occurrence of adenomyosis is correlated to bcl-2 expression regulated by estrogen and ER rather than genetic mutation.

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Condition tags

adenomyosis

MeSH descriptors

Adenomyoma Apoptosis Danazol Endometrial Neoplasms Estrogen Antagonists Gonadotropin-Releasing Hormone Gonadotropin-Releasing Hormone Adenomyoma Adenomyoma Adenomyoma Adenomyoma Adult Apoptosis Apoptosis bcl-2-Associated X Protein Danazol DNA, Neoplasm DNA, Neoplasm DNA, Neoplasm Endometrial Neoplasms

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europepmc
last seen: 2026-06-04T01:30:01.192114+00:00
openalex
last seen: 2026-06-04T00:00:01.174412+00:00
pubmed
last seen: 2026-05-13T22:12:32.173627+00:00
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