Regulation of angiogenic activity of human endometrial endothelial cells in culture by ovarian steroids

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Kayisli U., Luk J., Guzeloglu-Kayisli O., Seval Y., Demir R., Arici A.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, cilt.89, sa.11, ss.5794-5802, 2004 (SCI-Expanded)

Özet

Blood vessel growth and regression in human endometrium are regulated throughout the menstrual cycle. We sought a direct role of ovarian steroids on human endometrial endothelial cell (HEEC) proliferation and vascularization. To investigate the HEEC angiogenicity of sex steroids, we developed a reliable method for the isolation of HEEC, which allowed us to investigate the angiogenic effects of sex steroids using immunohistochemistry, immunocytochemistry, Western blot, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)2-(4-sulfophenyl)-2H-tetrazolium, inner salt proliferation, and vascular tube formation analyses. We were able to obtain 95-99% pure HEEC with our isolation technique. HEEC expressed predominantly estrogen receptor beta, minimally expressed estrogen receptor alpha, and but did not express progesterone (P-4) receptors A and B in vivo and in vitro. Estradiol (E-2; 10(-10)-10(-8) M) and P-4 (10(-12)-10(-8) M), alone or in combination, induced HEEC proliferation compared with control values after 48 h of treatment (P<0.05). Furthermore, after 8 d of treatment, there were significantly more angiogenic patterns in E-2 (10(-8) M), P-4 (10(-10) M), and E-2 plus P-4 (10(-8) and 10(-10) M) treatment groups compared with the control group ( angiogenic scores, 2.95 +/- 0.16, 3.26 +/- 0.16, 3.06 +/- 0.17, and 1.93 +/- 0.15, respectively; P<0.01). In conclusion, our results suggest that there are direct effects of E-2 and P-4 on HEEC and provide a new understanding of the physiological role of sex steroids in the regulation of endometrial events such as angiogenesis.