Although corticotropin-releasing hormone (CRH) and Fas ligand (FasL) have been documented in ovarian carcinoma, a clear association with tumour progression and immuno-escape has not been established. FasL plays an important role in promoting tumour cells' ability to counterattack immune cells. Here, we examined immunohistochemically the expression of CRH, CRHR1, CRHR2 and FasL in 47 human ovarian cancer cases. The ovarian cancer cell lines OvCa3 and A2780 were further used to test the hypothesis that CRH might contribute to the immune privilege of ovarian tumours, by modulating FasL expression on the cancer cells. We found that CRH, CRHR1, CRHR2 and FasL were expressed in 68.1, 70.2, 63.8 and 63.8% of the cases respectively. Positivity for CRH or FasL expression was associated with higher tumour stage. Finally, CRH increased the expression of FasL in OvCa3 and A2780 cells through CRHR1 thereby potentiated their ability to induce apoptosis of activated peripheral blood lymphocytes. Corticotropinreleasing hormone produced by human ovarian cancer might favour survival and progression of the tumour by promoting its immune privilege. These findings support the hypothesis that CRHR1 antagonists could potentially be used against ovarian cancer.

During ovarian follicular development in humans, only a limited number of follicles mature and ovulate. The vast majority of follicles stop developing after the formation of an antrum and then undergo atresia. The few that are selected to become ovulatory follicles are transformed into corpora lutea following ovulation. The lifespan of the corpus luteum is also limited. In each oestrus/menstrual cycle, corpora lutea regress and are eliminated by a progress called luteolysis. During atresia and luteolysis, granulosa and lutein cells undergo apoptosis. It is believed that there are many signal transduction pathways that control apoptosis in order to suppress full maturation of too many follicles and to protect the dominant follicle from the apoptotic process prior the ovulation. Such interplay between different factors, some of them produced in the ovary, may modulate apoptosis of corpus luteum cells, in order to preserve the function of the corpus luteum during pregnancy or to eliminate the old corpora lutea of the previous cycle. The present review reports a number of factors that regulate follicular atresia and corpus luteum regression, via apoptotic pathways. Elucidation of apoptotic mechanisms may lead to prevention of female infertility or other pathological conditions.

The formation of the corpus luteum (CL) is critical for the establishment of a successful pregnancy. After ovulation, the CL develops from the remnants of the ovulated ovarian follicle. This process, which involves varying cell-matrix interactions, is poorly characterized. To understand the role and potential regulation of cell-matrix interactions in the formation of the CL, we investigated the expression and activity of the matrix protein fibronectin (FN) and several of its integrin receptors on luteinized granulosa cells (GCs). In situ, FN and several FN-binding integrins were detected around luteinizing GCs during the early luteal phase, although expression declined in the late luteal phase. In vitro, GCs released FN, and stimulation of these cells with human chorionic gonadotropin increased the surface expression of FN, ␣ 5 ␤ 1 , and ␣ v ␤ 3 . Up-regulation of these proteins on GCs was reproduced by stimulation with vascular endothelial growth factor (VEGF) and was inhibited by anti-VEGF antibody. Lastly, expression of ␣ 5 ␤ 1 and ␣ v ␤ 3 mediated adhesion to FN, facilitated migration, and prevented apoptosis. These data suggest that in vivo luteogenic hormones, in part through a VEGF-dependent mechanism, stimulate selected integrin-matrix adhesive interactions that promote the motility and survival of GCs and thus contribute to the formation and preservation of the CL. (Am J

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