title: Dydrogesterone exerts endothelial anti-inflammatory actions decreasing expression of leukocyte adhesion molecules.
abstract: 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.
authors.affiliation: Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology, University of Pisa, Via Roma, 57, Pisa 56100, Italy.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Fu
authors.forename: Silvia
authors.initials: S
authors.lastname: Garibaldi
authors.forename: Santosh
authors.initials: S
authors.lastname: Gopal
authors.forename: Kinga
authors.initials: K
authors.lastname: Polak
authors.forename: Giulia
authors.initials: G
authors.lastname: Palla
authors.forename: Stefania
authors.initials: S
authors.lastname: Spina
authors.forename: Paolo
authors.initials: P
authors.lastname: Mannella
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Genazzani
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Genazzani
authors.forename: Tommaso
authors.initials: T
authors.lastname: Simoncini
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004394:Dydrogesterone / Q000031:analogs & derivatives / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D011372:Progestins / Q000494:pharmacology*
chemical_list: C514239:20-alpha-dihydrodydrogesterone; D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011372:Progestins; D004394:Dydrogesterone