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

• Published in: Molecular human reproduction 2008-04, Vol.14 (4), p.225-234
• Main Authors: Fu, Xiao-Dong, Flamini, Marina, Sanchez, Angel Matias, Goglia, Lorenzo, Giretti, Maria Silvia, Genazzani, Andrea R., Simoncini, Tommaso
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Membrane - drug effects; Cell Membrane - metabolism; cell movement; Cell Movement - drug effects; Cells, Cultured; Cytoskeleton - drug effects; Embryology: invertebrates and vertebrates. Teratology; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Immunoblotting; medroxyprogesterone acetate; Medroxyprogesterone Acetate - pharmacology; Microfilament Proteins - metabolism; moesin; Phosphorylation - drug effects; progesterone; Progesterone - pharmacology; Progestins - pharmacology; vascular endothelial cells
• ISSN: 1360-9947; 1460-2407
• DOI: 10.1093/molehr/gan010

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.