Expressão da angiotensina-(1-7), do receptor mas e da enzima conversora de angiotensina tipo 2 no endométrio humano

Abstract

Angiotensin (Ang)-(1-7) is a newly characterized member of therenin-angiotensin system, which has vasodilatory, anti-angiogenic and antiproliferative effects in several organs. Ang-(1-7) is produced from cleavage of Ang-II by angiotensin-converting-enzyme type 2 (ACE2), and acts through a specific G protein-coupled receptor, Mas. The aim of the present study was to investigate whether the human endometrium expresses Ang-(1-7), the receptor Mas, and the mRNA encoding ACE2 at different phases of menstrual cycle. By radioimmunoassay, Ang-(1-7) was detected in endometrial wash fluid at picomolar concentrations. Using immunofluorescence, both the peptide and its receptor were identified in cultured endometrial epithelial and stromal cells. Byimmunohistochemistry, Ang-(1-7) was localized in the endometrium throughout menstrual cycle, being more concentrated in the glandular epithelium of midand late secretory phase and in the stroma of early proliferative phase. This pattern corresponded to the ACE2 mRNA, which was significantly more abundant in epithelial cells than in stromal cells (2-fold increase, p<0.05) and in the secretory vs. proliferative phase (6.6-fold increase, p<0.01). The receptor Mas was equally distributed between epithelial and stromal cells and did not change during menstrual cycle. In conclusion, the vasoactive peptide Ang-(1-7),the enzyme involved in its synthesis and its receptor Mas are all expressed in the human endometrium, and the peptide is up-regulated during the secretory phase of menstrual cycle. The physiological role of this peptide system in normal and pathological endometrium warrants further investigation.