Dydrogesterone exerts endothelial anti-inflammatory actions decreasing expression of leukocyte adhesion molecules

• Published in: Molecular human reproduction Vol. 18; no. 1; pp. 44 - 51
• Main Authors: Fu, Xiao-Dong, Garibaldi, Silvia, Gopal, Santosh, Polak, Kinga, Palla, Giulia, Spina, Stefania, Mannella, Paolo, Genazzani, Andrea R., Genazzani, Alessandro D., Simoncini, Tommaso
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.01.2012
• Subjects: Active Transport, Cell Nucleus - drug effects; Anti-Inflammatory Agents - pharmacology; Cell Adhesion Molecules - metabolism; Dydrogesterone - analogs & derivatives; Dydrogesterone - pharmacology; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Female; Human Umbilical Vein Endothelial Cells; Humans; Lipopolysaccharides - pharmacology; NF-kappa B - metabolism; Progestins - pharmacology; NF-κB; endothelial cell, dydrogesterone; endothelial-leukocyte adhesion molecules; 20-α-dihydro-dydrogesterone
• ISSN: 1360-9947; 1460-2407
• DOI: 10.1093/molehr/gar062

Clinical observations and basic studies show that progesterone and progestins have a variable influence on endothelial function. Dydrogesterone (DG) is a widely used progestin, but its endothelial actions have not been thoroughly assessed. In this study, we investigated the effects of DG and its metabolite 20-α-dihydro-dydrogesterone (DHD), natural progesterone as well as medroxyprogesterone acetate, on the expression of leukocyte adhesion molecules in human endothelial cells using an in vitro experimental endothelial inflammation system. Our findings show that all progestins significantly suppress endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and inter-cellular adhesion molecule-1 (ICAM-1) induced by bacterial lypopolysaccharide (LPS). These inhibitory effects of DG and DHD require activation of progesterone receptor. DG and DHD decrease adhesion molecule expression associated with LPS administration by preventing nuclear translocation of the pro-inflammatory transcription factor nuclear factor-κB. In addition, DG and DHD do not alter the anti-inflammatory effects of 17β-estradiol. In conclusion, DG and DHD decrease endothelial inflammatory responses induced by LPS, via reduced expression of the pro-atherogenic adhesion molecules VCAM-1 and ICAM-1. These actions may be relevant for the vascular effects of DG.