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Mol. Hum. Reprod. Advance Access originally published online on February 27, 2008
Molecular Human Reproduction 2008 14(4):225-234; doi:10.1093/molehr/gan010
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Progestogens regulate endothelial actin cytoskeleton and cell movement via the actin-binding protein moesin

Xiao-Dong Fu{dagger}, Marina Flamini{dagger}, Angel Matias Sanchez, Lorenzo Goglia, Maria Silvia Giretti, Andrea R. Genazzani and Tommaso Simoncini1

Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Reproductive Medicine and Child Development, University of Pisa, Pisa 56100, Italy

1 Correspondence address. Tel: +39-050-553412; Fax: +39-050-553410; E-mail: t.simoncini{at}obgyn.med.unipi.it

The endothelial effects of progestogens are poorly investigated. Actin remodeling and cell movement are fundamental for endothelial function and are controlled by the actin-binding protein moesin. In this work, we studied the effects of progesterone and medroxyprogesterone acetate (MPA) on actin remodeling, moesin activation and cell movement in human endothelial cells. Our findings show that progesterone and MPA trigger a rapid endothelial actin rearrangement, with the formation of cortical actin complexes, pseudopodia and membrane ruffles. Both progestogens trigger a rapid progesterone receptor (PR)-dependent moesin activation via a non-genomic signaling cascade involving G proteins, the small GTPase RhoA and the Rho-associated kinase (ROCK-2). In addition, MPA signaling also requires the recruitment of phosphatidylinositol-3 kinase (PI3K). Both progestogens enhance endothelial cell migration, which is prevented by moesin silencing or by blockade of PR, G proteins, PI3K, mitogen-activated protein kinases or ROCK-2. Progesterone and MPA potentiate 17β-estradiol (E2) induced-moesin activation. However, they partially reduce cell migration induced by E2. In conclusion, progesterone and MPA regulate endothelial cell movement by rapidly signaling to the actin-binding protein moesin and to the actin cytoskeleton. These findings provide new information on the biological actions of progestins on human endothelial cells that are relevant for vascular function.

Key words: progesterone/medroxyprogesterone acetate/vascular endothelial cells/moesin/cell movement

{dagger} These two authors contributed equally to this work.

Submitted on December 13, 2007; resubmitted on February 9, 2008; accepted on February 22, 2008.


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