Role of estrogen receptors in menstrual cycle-related neoangiogenesis and their influence on endothelial progenitor cell physiology

OBJECTIVE: To study whether estrogen receptors (ERs) are expressed in vitro and in vivo by female circulating endothelial progenitor cells (EPCs); and the role of ERs in the periodic vascular damage and repair that occurs during the menstrual cycle. DESIGN: Quantification of circulating progenitor cells, EPCs, and relative CXCR4+ fraction by flow cytometry. Quantification of plasma 17beta-E(2) by electrochemiluminescent immunoassay. Expression of ERs by immunofluorescence and immunohistochemistry. Estrogen receptor, CXCR4, and matrix metalloproteinase 9 gene expression by reverse transcriptase-polymerase chain reaction and real-time polymerase chain reaction. SETTING: University clinic and academic research laboratory. PATIENT(S): Twelve young fertile women (aged 22-27 years) observed for 6 months, 10 postmenopausal women (aged 52-63 years), and 50 male control subjects (aged 24-61 years). INTERVENTION(S): Blood (35 mL) was collected at each observation point. MAIN OUTCOME MEASURE(S): Correlation between 17beta-E(2) exposure and neoangiogenesis markers. RESULT(S): Estrogen receptors are expressed both in cultured EPCs after prolonged estrogen stimulation and in circulating EPCs, such as in CD34+ cells in bone marrow. The number of ER-beta+ and CXCR4+ EPCs increased during the ovulatory phase, and this increase is probably mediated by ER-beta and matrix metalloproteinase 9. CONCLUSION(S): Estrogens play a key role in neoangiogenesis processes, such as endometrium recovery, and this mechanism involves both a central action (on bone marrow) and a cytokine-mediated peripheral one (on endothelium).