Cell proliferation effect of GnRH agonist on pathologic lesions of women with endometriosis, adenomyosis and uterine myoma

Background: We recently demonstrated the effect of gonadotropin-releasing hormone agonist (GnRHa) on tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma. Here, we investigated expression of GnRH receptors (GnRHR) and effect of GnRHa on the proliferation of cells derived from endometria and pathologic lesions of women with these reproductive diseases. Methods: Biopsy specimens were collected from pathologic lesions and corresponding endometria of 35 women with pelvic endometriosis, 45 women with ovarian endometrioma, 35 women with adenomyosis, 56 women with uterine myoma during laparoscopy or laparotomy. The gene and protein expressions of GnRHR in eutopic/ectopic cells and tissues were examined by reverse transcriptase-polymerase chain reaction and immunohistochemistry. The immunoreactivity pattern of GnRHR expression in respective tissue was analyzed by quantitative-histogram (Q-H) scores. The exogenous effect of GnRHa on cell proliferation was examined by 5-Bromo-2-deoxyuridine incorporation assay. The Ki-67-immunoreactive cell proliferation index was analyzed in biopsy specimens derived from GnRHa-treated and -non-treated women. Khan KN et al., Page 3 Results: GnRH receptors, type I and type II, mRNAs and GnRHR proteins were expressed in eutopic endometria and pathologic lesions derived from women with endometriosis, adenomyosis and uterine myoma. GnRHR expression was the highest in the menstrual phase when compared with other phases of the menstrual cycle. The highest Q-H scores of GnRHR immunoreaction were found in blood-filled opaque red lesions than in other peritoneal lesions. The exogenous treatment with GnRHa significantly suppressed the proliferation of cells derived from respective endometria and pathologic lesions when compared with GnRHa-non-treated cells. Conclusion: Local tissue expressions of GnRH receptor were detected in endometriosis, adenomyosis and uterine myoma. In addition to hypo-estrogenic effect, direct anti-proliferative effect of GnRHa may be involved in the regression of these reproductive diseases with consequent remission of clinical symptoms.