Gonadotropin-releasing hormone analog repairs reduced endometrial cell apoptosis in endometriosis in vitro.
OBJECTIVE
Impaired sensitivity of endometrial tissue to spontaneous apoptosis in women with endometriosis contributes to the abnormal implantation and growth of endometrium at ectopic sites. Our purpose was to examine the effect of gonadotropin-releasing hormone analog, widely used in the treatment of endometriosis, on the reduced rate of endometrial apoptosis in endometriosis.


METHODS
Paired ectopic and eutopic endometrial tissue specimens were obtained from 13 patients with endometriosis, and control samples were taken from 8 patients with uterine myoma. Apoptotic cell death was assessed biochemically and morphologically with an enzyme-linked immunoassay and Hoechst No. 33342 staining of deoxyribonucleic acid fragment, respectively.


RESULTS
Spontaneous apoptosis was significantly lower in ectopic and eutopic endometrial tissue from patients with endometriosis (0.22 +/- 0.082 in absorbance) than in endometrial tissue from control subjects (0.52 +/- 0.483)(P < 0.001). Incubation with a gonadotropin-releasing hormone analog (1 micromol/L) increased the apoptotic rate of endometrial cells from patients with endometriosis to 0.56 +/- 0.501 (P <.001). The effect of this gonadotropin-releasing hormone revealed a dose dependency; a half-maximal effect occurred with 10 nmol/L; however, the control endometrium was not affected.


CONCLUSIONS
Exposure to gonadotropin-releasing hormone results in changes of the sensitivity of endometriotic endometrium to spontaneous apoptosis; these changes in sensitivity may, in turn, release endometrial cells from resistance to apoptosis and result in reduced survival and growth. This phenomenon could, at least in part, account for the therapeutic action of gonadotropin-releasing hormone analog on endometriosis.
Imai
A
A
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
Takagi
A
A
Tamaya
T
T
D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles; D002064:Buserelin / Q000494:pharmacology*; D004396:Coloring Agents; D053938:DNA Fragmentation; D004715:Endometriosis / Q000473:pathology*; D004717:Endometrium / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D016729:Leuprolide / Q000494:pharmacology*; D011419:Propidium
D001562:Benzimidazoles; D004396:Coloring Agents; D005456:Fluorescent Dyes; D011419:Propidium; D016729:Leuprolide; C017807:bisbenzimide ethoxide trihydrochloride; D002064:Buserelin