Regulation of Vascular Endothelial Growth Factor in endometrial tumour cells by resveratrol and EGCG.

OBJECTIVE: Our purpose was to establish whether resveratrol and (-)-epigallocatechin-3-gallate (EGCG), two compounds extracted from food, would reduce the amount of Vascular Endothelial Growth Factor (VEGF) secreted into the supernatants of cultured endometrial cancer cells. STUDY DESIGN: Endometrial cancer samples were collected from 19 consenting women who were undergoing hysterectomy operations to remove tumours. Tumour cells were dispersed into single cell suspensions and cultured. Two immortalised cell lines were also studied. After incubating cells under various test and control conditions, ELISA was used to measure VEGF levels in the supernatants. RESULTS: VEGF was measurable at varied concentrations in the supernatants of cultured cells, from both cell lines and primary cultures. Cobalt chloride (CoCl(2)), a hypoxia mimic, increased the measured secretion of VEGF from these cells. In contrast, treatment with either resveratrol or EGCG significantly reduced secretion of VEGF. Further, resveratrol and EGCG inhibited release from cells that were also exposed to CoCl(2). CONCLUSION: Both resveratrol and EGCG induced significant reductions in the amount of VEGF secreted into the supernatant of cultured endometrial cancer cells. These results suggest that resveratrol and EGCG may have the potential to inhibit angiogenesis in endometrial tumours. Further investigation of these substances in endometrial cancer is warranted.

Effects of galanin and leptin on gonadotropin-releasing hormone-stimulated luteinizing hormone release from the pituitary.

BACKGROUND: A number of peptides regulate luteinizing hormone (LH) release. In some cases, these peptides exert an effect at the pituitary, to directly regulate LH release and/or to modulate the effects of gonadotropin-releasing hormone (GnRH). A link between nutrition and reproductive function is well established. In this study we investigated the effects of two peptides associated with appetite control, galanin and leptin, on the regulation of LH release from the pituitary. METHODS: Using perifused anterior pituitary tissue from freely fed rats, we investigated the effect of galanin on basal LH release and GnRH-stimulated LH release from pituitaries in a high-estrogen (proestrus) and a low-estrogen (metestrus) environment. In addition, we examined the effect of galanin on LH release following GnRH self-priming. The effect of inhibiting protein synthesis, with cycloheximide, was also studied under these conditions. Finally, the effects of leptin alone and on a galanin-modulated LH response were investigated. RESULTS: There was no detectable effect of leptin, either alone or in conjunction with galanin. We observed that galanin enhanced GnRH stimulation of LH secretion, an effect that was dependent on protein synthesis and on an estrogenized environment. In addition, importantly, galanin also enhanced the LH response in GnRH self-primed pulses. CONCLUSION: Our results provide further details on the effect of galanin on the LH surge, particularly the effect on the response to pulsatile GnRH and the effect of protein production, and thereby indicate a means by which appetite- and nutrition-related peptides may act on the ovulatory cycle at the pituitary.