Expression of apoptosis-related proteins in adenomyotic uteri treated with danazol and GnRH agonists.
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.
Ueki
Ken
K
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Japan.
Kumagai
Koji
K
Yamashita
Hidetoshi
H
Li
Zhong-lian
ZL
Ueki
Minoru
M
Otsuki
Yoshinori
Y
D018194:Adenomyoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D003613:Danazol / Q000494:pharmacology*; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D053222:Fas Ligand Protein; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D008597:Menstrual Cycle; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000096:biosynthesis / Q000378:metabolism
D004273:DNA, Neoplasm; D004965:Estrogen Antagonists; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D007987:Gonadotropin-Releasing Hormone; C083781:LHRH, Ala(6)-Gly(10)-ethylamide-; D003613:Danazol