Cell proliferation effect of GnRH agonist on pathological lesions of women with endometriosis, adenomyosis and uterine myoma.
BACKGROUND
We recently demonstrated the effect of gonadotrophin-releasing hormone agonist (GnRHa) on tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma. Here, we investigated expression of GnRH receptors (GnRHRs) and effect of GnRHa on the proliferation of cells derived from endometria and pathological lesions of women with these reproductive diseases.


METHODS
Biopsy specimens were collected from lesions and corresponding endometria of 35 women with pelvic endometriosis, 45 women with ovarian endometrioma, 35 women with adenomyosis and 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 (RT-PCR) and immunohistochemistry. The immunoreactivity of GnRHR in tissue was analysed 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 analysed in biopsy specimens derived from GnRHa-treated and -non-treated women.


RESULTS
Types I and II GnRHRs mRNA and proteins were expressed in eutopic endometria and pathological 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. Higher Q-H scores of GnRHR immunoreaction were found in blood-filled opaque red lesions than in other peritoneal lesions. Exogenous treatment with GnRHa significantly suppressed the proliferation of cells derived from respective endometria and pathological lesions when compared with GnRHa-non-treated cells.


CONCLUSIONS
Local tissue expression of GnRHR was detected in endometriosis, adenomyosis and uterine myoma. In addition to a hypo-estrogenic effect, a direct anti-proliferative effect of GnRHa may be involved in the regression of these reproductive diseases with consequent remission of clinical symptoms.
Khan
Khaleque Newaz
KN
Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, Japan. nemokhan@nagasaki-u.ac.jp
Kitajima
Michio
M
Hiraki
Koichi
K
Fujishita
Akira
A
Nakashima
Masahiro
M
Ishimaru
Tadayuki
T
Masuzaki
Hideaki
H
D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects*; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D007889:Leiomyoma / Q000378:metabolism / Q000473:pathology*; D016729:Leuprolide / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D011966:Receptors, LHRH / Q000096:biosynthesis*; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology*
D019394:Ki-67 Antigen; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide