Regulated expression of the renin-angiotensin-system in human granulosa lutein cells: angiotensin II increases VEGF expression but its synthesis is reduced by hCG.
BACKGROUND
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.


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.


CONCLUSIONS
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.
Herr
Daniel
D
Department of Obstetrics and Gynaecology, Ulm University Medical Centre, Prittwitzstrasse 43, 89075 Ulm, Germany.
Duncan
W Colin
WC
Hack
Gerda
G
Konrad
Regina
R
Kreienberg
Rolf
R
Wulff
Christine
C
D000804:Angiotensin II / Q000502:physiology*; D002478:Cells, Cultured / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D008184:Luteal Cells / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II