HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.06-6840comv1 21/1/265    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zerr-Fouineau, M. Articles by Schini-Kerth, V. B. Search for Related Content PubMed PubMed Citation Articles by Zerr-Fouineau, M. Articles by Schini-Kerth, V. B.

Progestins overcome inhibition of platelet aggregation by endothelial cells by down-regulating endothelial NO synthase via glucocorticoid receptors

Murielle Zerr-Fouineau^*, Marta Chataigneau^*, Christian Blot and Valérie B. Schini-Kerth^*,1

^* Département de Pharmacologie et Physico-Chimie, UMR 7175-LC1, Université Louis Pasteur de Strasbourg, France; and

Théramex, Monaco

¹Correspondence: UMR CNRS 7175-LC1, Université Louis Pasteur de Strasbourg, Faculté de Pharmacie, 74, route du Rhin, B.P. 60024, F-67401 Illkirch, France. E-mail: valerie.schini-kerth{at}pharma.u-strasbg.fr

Hormone replacement therapy with estroprogestin preparations is associated with an increased risk of venous and arterial thromboembolic events in postmenopausal women. This study examined whether progestins affect the formation of NO in endothelial cells, and, if so, to determine the underlying mechanism. Experiments were performed with human umbilical vein endothelial cells. Endothelial nitric oxide synthase (eNOS) expression was assessed by real-time polymerase chain reaction (PCR) and Western blot analysis, NO formation by electron spin resonance spectroscopy, nuclear translocation of the glucocorticoid receptor by immunofluorescence microscopy, and platelet aggregation by an aggregometer. Medroxyprogesterone acetate (MPA) and progesterone markedly decreased the eNOS mRNA and protein levels, whereas levonorgestrel and nomegestrol acetate had only small effects. This effect was associated with a decreased NO formation leading to a reduced ability of endothelial cells to prevent platelet aggregation and was prevented by knockdown of the glucocorticoid receptor using siRNA. MPA and progesterone, but not levonorgestrel and nomegestrol acetate, caused nuclear translocation of the glucocorticoid receptor. The present findings indicate that certain progestins, including MPA, reduce the antiaggregatory effect of endothelial cells by decreasing the expression of eNOS and the formation of NO in endothelial cells, an effect that is mediated via activation of glucocorticoid receptors.—Zerr-Fouineau, M., Chataigneau, M., Blot, C., Schini-Kerth, V. B. Progestins overcome inhibition of platelet aggregation by endothelial cells by down-regulating endothelial NO synthase via glucocorticoid receptors.

Key Words: thrombosis • hormone replacement • therapy • contraception

This article has been cited by other articles:

				I. C Villar, A. J Hobbs, and A. Ahluwalia Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor J. Endocrinol., June 1, 2008; 197(3): 447 - 462. [Abstract] [Full Text] [PDF]