Up-regulation of apoptosis by gonadotrophin-releasing hormone agonist in cultures of endometrial cells from women with symptomatic myomas.
BACKGROUND
The aim of the present study was to evaluate the effect of gonadotrophin-releasing hormone agonist (GnRH-a), which is widely used in the medical treatment of symptomatic myomas, on the rate of endometrial cell apoptosis in cultures from women with symptomatic myomas.


METHODS
The study included 36 women with symptomatic myomas without endometrial hyperplasia or endometrial carcinoma, and 22 controls. Endometrial biopsy specimens were obtained from all subjects. Levels of apoptosis were examined in epithelial endometrial cell cultures before and after incubation with GnRH-a (triptorelin). The percentage of apoptotic cells was evaluated using the terminal deoxynucleotidyl transferase-mediated d-UTP nick end labeling assay and flow cytometry was used to evaluate Annexin V levels.


RESULTS
Levels of spontaneous apoptosis were significantly lower in endometrial cultures from patients with symptomatic myomas than in those from control subjects (P < 0.01). Concentrations as low as 10(-7) M GnRH-a enhanced apoptosis in endometrial cultures from patients with symptomatic myomas (3.48% +/- 0.27% apoptotic cells in untreated samples and 25.45 +/- 0.95% in cells treated with 10(-7) M GnRH-a; P <0.01). The percentage of apoptotic cells also increased when cultures from control women were treated with GnRH-a (8.10 +/- 0.18% in untreated samples and 15.29 +/- 2.30% in treated samples; P <0.01). Levels of apoptosis were dependent on both dose of GnRH-a and time of treatment.


CONCLUSIONS
GnRH-a stimulates apoptosis in endometrial cells from patients with symptomatic myomas and this could, at least in part, account for the therapeutic action of GnRH-a.
Kang
Jia-Li
JL
Department of Obstetrics and Gynecology, The Guangzhou First Municipal People's Hospital Affiliated to Guangzhou Medical College, 1 Panfu Road, Yuexiu District, Guangzhou, People's Republic of China.
Wang
Dong-Yu
DY
Wang
Xiao-Xia
XX
Yu
Jia
J
D000328:Adult; D017304:Annexin A5 / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001706:Biopsy; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007889:Leiomyoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009994:Osmolar Concentration; D013997:Time Factors; D017329:Triptorelin Pamoate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*; D014592:Uterine Hemorrhage / Q000517:prevention & control
D017304:Annexin A5; D018931:Antineoplastic Agents, Hormonal; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone