on December 18, 2008
Published online before print December 18, 2008, doi: 10.1161/ATVBAHA.108.178004
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 26, 2008
Accepted on December 7, 2008
Certain Progestins Prevent the Enhancing Effect of 17
-Estradiol on NO-Mediated Inhibition of Platelet Aggregation by Endothelial Cells
Murielle Zerr-Fouineau ;
From the Département de Pharmacologie et Physico-Chimie (M.Z.-F., M.J., C.B., C.B., V.B.S.-K.), UMR CNRS 7175, Institut Gilbert Laustriat, Université Louis Pasteur Strasbourg I, Illkirch, France; and the Institute of Physiology and Pathophysiology (M.H.), University of Heidelberg, Germany.
* To whom correspondence should be addressed. E-mail: valerie.schini-kerth{at}pharma.u-strasbg.fr.
Objectives—Estro-progestin treatments have been associated with an increased risk of thromboembolic events in postmenopausal women. This study examined whether progestins affect the stimulatory effect of estrogens on the endothelial formation of nitric oxide (NO), a potent antithrombotic factor.
Methods and Results—Experiments were performed with human endothelial cells. Endothelial NO synthase (eNOS) and GTP cyclohydrolase I (GTPCH I) mRNA expression was assessed by RT-PCR, eNOS protein by Western blotting, NO formation by electron spin resonance spectroscopy, and platelet aggregation by an aggregometer. Medroxyprogesterone acetate (MPA), progesterone, levonorgestrel, and nomegestrol acetate prevented the 17
-estradiol (17-E)–induced expression of eNOS mRNA and protein. MPA and progesterone reduced the 17-E–induced formation of NO and potentiation of the inhibitory effect of endothelial cells on platelet aggregation whereas levonorgestrel and nomegestrol acetate were without effect. Moreover, MPA and progesterone prevented the 17-E–induced expression of GTPCH I mRNA. Mifepristone, a glucocorticoid and progesterone receptor antagonist, and L-sepiapterin prevented the inhibitory effect of MPA and progesterone on platelet aggregation.
Conclusions—Certain progestins, including MPA, attenuate the 17-E–induced NO-mediated inhibition of platelet aggregation by endothelial cells through preventing both eNOS and GTPCH I expression most likely via activation of glucocorticoid receptors.
Key words: 17
-estradiol •
progestins •
endothelial nitric oxide synthase •
GTP cyclohydrolase •
thrombosis
Related Article:
- Interference of Progestins With Endothelial Actions of Estrogens: A Matter of Glucocorticoid Action or Deprivation?
- J.F. Arnal, P. Gourdy, and T. Simoncini
Arterioscler Thromb Vasc Biol 2009 29: 441-443.[Extract] [Full Text] [PDF]
This article has been cited by other articles:
 |
|
 |
|
  L. Gao, Y.-F. Pung, J. Zhang, P. Chen, T. Wang, M. Li, M. Meza, L. Toro, and H. Cai Sepiapterin reductase regulation of endothelial tetrahydrobiopterin and nitric oxide bioavailability Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H331 - H339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.F. Arnal, P. Gourdy, and T. Simoncini Interference of Progestins With Endothelial Actions of Estrogens: A Matter of Glucocorticoid Action or Deprivation? Arterioscler Thromb Vasc Biol, April 1, 2009; 29(4): 441 - 443. [Full Text] [PDF]
|
|