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Regulation of Vascular Endothelial Growth Factor Synthesis and Release by Human Luteal Cells in Vitro

Cattedra di Fisiopatologia della Riproduzione Umana (A.T., F.Mic., F.Min., M.O., M.F.G., F.R., S.M., R.A.), Istituto Scientifico Internazionale "Paolo VI" (F.T.), and Istituto di Farmacologia (P.N.), Università Cattolica del Sacro Cuore, 00168 Roma, Italy; and Istituto di Ricerca "Associazione OASI Maria SS ONLUS" (S.C., A.L.), 94018 Troina (EN), Italy

Address all correspondence and requests for reprints to: Rosanna Apa, M.D., Cattedra di Fisiopatologia della Riproduzione Umana, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Roma, Italia. E-mail: krimisa{at}libero.it.

Context: Vascular endothelial growth factor (VEGF) is essential for normal luteal development and function, but little is still known about the regulation of its production by human midluteal phase luteal cells.

Objective: We investigated whether human chorionic gonadotropin (hCG) or local factors, including chemical hypoxia, IGF-I and IGF-II, prostaglandin (PG)E₂, and PGF₂ prevail in modulating VEGF mRNA and protein production in human midluteal phase luteal cells. The effect of progesterone (P) on luteal VEGF mRNA expression and protein secretion was also evaluated. Finally, we investigated whether VEGF could directly affect luteal P secretion.

Interventions: In human midluteal phase luteal cells, VEGF mRNA expression was evaluated by semiquantitative RT-PCR, whereas VEGF and P release was evaluated by ELISA and RIA, respectively.

Results: hCG was unable to significantly affect luteal VEGF mRNA and protein synthesis, which in turn was significantly increased by both chemical hypoxia and IGFs. Conversely, VEGF mRNA and protein production was reduced by PGs and P. Finally, VEGF did not affect P luteal secretion.

Conclusions: Our results suggest that local ovarian factors, rather than hCG, predominate in regulating VEGF mRNA and protein production by human midluteal phase luteal cells. For VEGF, a lack of a direct luteal steroidogenic effect was also demonstrated.

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