Genomic and non-genomic effects of estrogens on endothelial cells.
Estrogen receptors act via the regulation of transcriptional processes, involving nuclear translocation and binding on specific response elements, thus leading to regulation of target gene expression. However, novel non-transcriptional mechanisms of signal transduction through steroid hormone receptors have been identified. These so-called "non-genomic" effects are independent by gene transcription or protein synthesis and involve steroid-induced modulation of cytoplasmic or of cell membrane-bound regulatory proteins. Relevant biological actions of steroids have been associated with this signaling in different tissues. Ubiquitary regulatory cascades such as mitogen-activated protein kinases (MAPK), the phosphatidylinositol 3-OH kinase (PI3K) and tyrosine kinases are modulated through non-transcriptional mechanisms by steroid hormones. Furthermore, steroid hormone receptors modulation of cell membrane-associated molecules such as ion channels and G-protein-coupled receptors has been shown in diverse tissues. The vascular wall is a site where non-genomic steroid hormones actions are particularly prominent. For instance, estrogens and glucocorticoids trigger rapid vasodilatation due to rapid induction of nitric oxide synthesis in endothelial cells via the estrogen receptor-dependent activation of MAPK and PI3K, leading to relevant pathophysiological consequences, in vitro and in vivo. The growing amount of evidence collected in the last years claims that non-transcriptional signaling mechanisms play a primary role in the generation of the effects of steroids on endothelial cells, which may turn out to be of relevance for clinical purposes.
Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology, University of Pisa, Via Roma 67, 56100 Pisa, Italy. t.simoncini@obgyn.med.unipi.it
Tommaso
T
Simoncini
Paolo
P
Mannella
Letizia
L
Fornari
Antonella
A
Caruso
Gaetano
G
Varone
Andrea Riccardo
AR
Genazzani
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004967:Estrogens / Q000502:physiology*; D005938:Glucocorticoids / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology
D004967:Estrogens; D005938:Glucocorticoids; D007473:Ion Channels; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases