GnRH II as a possible cytostatic regulator in the development of endometriosis

Human Reproduction · 2005 · vol. 20(11) , pp. 3212–3218 · doi:10.1093/humrep/dei192 · PMID:16037111 · W2158274066
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GnRH II suppresses proliferation and inflammation in endometrial stromal cells, and its reduced expression in women with endometriosis suggests impaired cytostatic regulation.

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Abstract

BACKGROUND: GnRH II is the second form of GnRH and is widely distributed in peripheral tissues of the female reproductive tract as well as in the central nervous system. In the present study, we studied the possible implication of GnRH II in endometriosis. METHODS: Effects of GnRH II on 5-bromo-2'-deoxyuridine (BrdU) uptake by cultured endometriotic stromal cells were examined. Effects of GnRH II on interleukin (IL)-1beta-induced expression of cyclooxygenase (COX)-2 and IL-8 were also studied. mRNA levels of GnRH I, GnRH II, type I GnRH receptor and type II GnRH receptor were determined by real-time quantitative RT-PCR in endometrial tissues of women with or without endometriosis and in endometriotic tissues. RESULTS: GnRH II dose-dependently suppressed BrdU uptake by endometrial stromal cells. Treatment with IL-1beta markedly increased mRNA levels of COX-2 and IL-8 in endometrial stromal cells and IL-8 protein secretion by these cells, while these increments were significantly suppressed by supplementation with GnRH II. The mRNA levels of GnRH II were lower in endometrial and endometriotic tissues of women with endometriosis than in endometrial tissues of women without endometriosis, both in the proliferative phase and the secretory phase. In addition, as for GnRH I, type I GnRH receptor and type II GnRH receptor, the mRNA levels were lower in endometrial tissues of women with endometriosis than in those without endometriosis in the secretory phase. CONCLUSIONS: In the light of the demonstrated antiproliferative and anti-inflammatory effects of GnRH II on endometrial stromal cells, the lower expression of GnRH II in eutopic and ectopic endometrium of women with endometriosis suggests that endogenous GnRH II-mediated cytostatic regulation may be impaired in the development of endometriosis.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Gonadotropin-Releasing Hormone Adult Bromodeoxyuridine Bromodeoxyuridine Cell Proliferation Cell Proliferation Cells, Cultured Cyclooxygenase 2 Cyclooxygenase 2 Endometriosis Endometrium Endometrium Female Gonadotropin-Releasing Hormone Gonadotropin-Releasing Hormone Humans Interleukin-1 Interleukin-1 Interleukin-8

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