Estrogen has a cardiovascular protective role in women due in part to its effect on the vasculature. The roles of the two estrogen receptors (ERs), ERα and ERβ, in the vascular actions of estrogen are unclear, as are effects of estrogen on microvascular endothelial cells (MEC) derived from sex steroid-responsive tissues. The present study demonstrates that 17β-estradiol, but not progesterone, increases vascular endothelial growth factor (VEGF) receptor (VEGFR) expression on human myometrial MEC measured using biotin-recombinant human (rh) VEGF165 and flow cytometry. This response occurred in a time- and dose-dependent manner, with significantly increased rhVEGF165 binding at 3 h and maximal responses between 0.1 and 10 nmol/liter 17β-estradiol, which was blocked by the antiestrogen ICI 182,780. Approximately 60% of samples demonstrated this response to 17β-estradiol. All samples of myometrial MEC expressed both ERβ mRNA and protein demonstrated by semiquantitative RT-PCR and Western blotting. However, ERα mRNA and protein were expressed in only 13 of 21 MEC samples. There was a significant association between ERα expression in myometrial MEC and their ability to respond to 17β-estradiol by increasing rhVEGF165 binding. 17β-estradiol increased VEGFR-2 expression in ERα-expressing MEC isolates, which also demonstrated increased rhVEGF165 binding, but failed to have these effects on ERα negative samples. Similarly, 17β-estradiol augmented VEGF-induced MEC proliferation in ERα-expressing MEC samples, which was blocked by ICI 182,780. These observations suggest that 17β-estradiol increases VEGFR-2 expression on human myometrial MEC promoting endothelial cell proliferation, an effect that varies between subjects and appears to be mediated primarily by ERα.
|Number of pages||9|
|Journal||The Journal of Clinical Endocrinology and Metabolism|
|Publication status||Published - Sep 2002|