Role of gonadotropin-releasing hormone in the ovarian cells.

摘要

Considering the extrapituitary roles for gonadotropin-releasing hormone (GnRH) in reproductive tissues, the present study investigated role of GnRH in the ovarian cells. The GnRH and GnRH receptor (GnRHR) mRNA were expressed and autoregulated in a biphasic manner by a GnRH agonist (GnRH-a) in human ovarian surface epithelium (hOSE) cells and an ovarian cancer cell line, OVCAR-3. The GnRH-a had a receptor-mediated growth inhibitory effect in both cell types. The growth inhibitory effect was associated with apoptosis in OVCAR-3 cells. In addition, 17beta-estradiol induced a significant down-regulation of GnRH mRNA in OVCAR-3, but not in hOSE cells and of GnRHR mRNA in both hOSE and OVCAR-3 cells. Pre- or cotreatment with 17beta-estradiol significantly attenuated the growth inhibitory effect of the GnRH-a in OVCAR-3 cells, but not in hOSE cells. These results strongly support the presence of functional autocrine GnRH/GnRHR loop and potential interaction with estrogen/estrogen receptor.; The GnRH-a stimulated MAPK activation in human granulosa-luteal cells (hGLCs) via a PKC-dependent pathway, which mediated the inhibitory effect of GnRH-a in progesterone secretion. The GnRH-a also stimulated MAPK activation in OVCAR-3 cells, normal placenta-derived cells (IEVT) and placental carcinoma (JEG-3) cells. The GnRH-induced MAPK activation mediated the growth inhibitory effect of GnRH-a in OVCAR-3 cells, but not the stimulatory effect of GnRH-a on the KG mRNA level in JEG-3 cells. These results demonstrated that GnRH stimulated MAPK activation that mediated the cellular functions of GnRH in normal and neoplastic cells of human ovary.; The present study demonstrates that one mechanism by which cell-specific expression of the human GnRHR is achieved is through the binding of distinct cell-specific regulatory factors to various promoter elements in the 5 '-flanking region of the gene.; In this study, the second form of GnRH (GnRH-II) and GnRH-I differentially regulated GnRHR and its ligands. Gonadotropins also differentially regulated (GnRH-II) and GnRH-I mRNA levels. (GnRH-II) inhibited basal and hCG-stimulated progesterone secretion. The antigonadotropic effect of GnRH-II was mediated through down-regulating gonadotropin receptors without affecting cAMP levels.; In summary, on the basis of the expression, differential regulation and/or functional roles of GnRH, our studies strongly support the notion that an intrinsic GnRH axis plays an important role in regulating normal and malignant ovarian cell functions.