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Regulated expression of the Renin-Angiotensin-System in human granulosa lutein cells: Angiotensin II increases VEGF expression but its synthesis is reduced by hCG

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Abstract

Introduction

The Renin-Angiotensin-System (RAS) has been suspected not only to control vascular tone but also to regulate angiogenesis. Angiotensin II has been shown to influence angiogenic factors such as vascular endothelial growth factor (VEGF). The Corpus luteum undergoes intense VEGF-dependent angiogenesis, regulated by luteinising hormone (LH) and human chorionic gonadotrophin (hCG). We therefore hypothesised, that locally produced Angiotensin II could act as a physiological co-regulator with hCG in luteal VEGF expression.

Materials and methods

We investigated the expression of RAS components and their regulation by hCG in human granulosa lutein cells using RT-PCR, immunocytochemistry and Western blotting. In addition, we studied the effect of Angiotensin II on basal and hCG-stimulated VEGF expression using TaqMan-analysis, ELISA, and Western blot analysis.

Results

Human granulosa lutein cells express angiotensinogen and angiotensin converting enzyme (ACE) and synthesise Angiotensin. In addition, they express both Angiotensin receptors. Angiotensin II stimulated VEGF mRNA (p < 0.05) and protein expression (p < 0.05). However, hCG decreased angiotensinogen (p < 0.05) and Angiotensin II (p < 0.05). Both, the addition of Angiotensin II and its inhibition using Candesartan did not change the magnitude of hCG-increased VEGF expression.

Conclusion

These findings suggest a role for locally synthesised Angiotensin II in the regulation of luteal VEGF expression. However, Angiotensin II does not appear to have a major contribution in the presence of hCG when the RAS pathway is down-regulated.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Ulm University Medical Centre, Prittwitzstrasse 43, 89075, Ulm, Germany

    Daniel Herr, Gerda Hack, Regina Konrad, Rolf Kreienberg & Christine Wulff

  2. Obstetrics and Gynaecology, Department of Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh, Scotland, UK

    W. Colin Duncan

  3. Universitäts-Frauenklinik Ulm, Prittwitzstr. 43, 89075, Ulm, Germany

    Christine Wulff

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  1. Daniel Herr
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  2. W. Colin Duncan
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Correspondence to Christine Wulff.

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Herr, D., Duncan, W.C., Hack, G. et al. Regulated expression of the Renin-Angiotensin-System in human granulosa lutein cells: Angiotensin II increases VEGF expression but its synthesis is reduced by hCG. Arch Gynecol Obstet 281, 409–416 (2010). https://doi.org/10.1007/s00404-009-1135-8

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