scholarly journals Minireview: Rapid Actions of Sex Steroids in the Endothelium

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2411-2422 ◽  
Author(s):  
Renee W. Y. Chow ◽  
David J. Handelsman ◽  
Martin K. C. Ng

The endothelium is a dynamic interface between the blood vessel and the circulating blood that plays a pivotal role in vascular homeostasis. As such, studies on sex steroid regulation of endothelial function are critical to understanding the role of sex steroids in cardiovascular health and disease. The classical model of steroid action involves liganded steroid receptors binding to specific response elements on target genes to regulate gene transcription. In whole organisms, the time lag between steroid administration and observable effects produced by newly synthesized protein is typically in the order of hours to days. And yet, some effects of steroids, such as vasodilatation, occur within seconds to minutes of steroid administration. Studies in multiple cell types have also shown that steroids can cause the rapid initiation of multiple signaling cascades and second messenger systems, prompting investigations into alternate, transcription independent mechanisms of steroid action. Studies of the endothelium over the past two decades have revealed fundamental mechanisms in rapid sex steroid signaling. In particular, endothelium-dependent vasodilatation by estradiol-induced activation of endothelial nitric oxide synthase has proven to be an uniquely informative model to study sex steroid signaling via classical sex steroid receptors localized to the cell membrane. Despite the complexity of feedback and cross talk between rapid sex steroid signaling and other modes of steroid action, recent studies in this field are facilitating the development of steroidal drugs that selectively target the ability of sex steroids to initiate signaling cascades.

2010 ◽  
Vol 4 (4) ◽  
pp. 161-172 ◽  
Author(s):  
Tiziana Giraldi ◽  
Pia Giovannelli ◽  
Marzia Di Donato ◽  
Gabriella Castoria ◽  
Antimo Migliaccio ◽  
...  

2014 ◽  
Vol 307 (2) ◽  
pp. E133-E140 ◽  
Author(s):  
Ellis R. Levin

Steroid receptors exist and function in multiple compartments of cells in most organs. Although the functions and nature of some of these receptors is being defined, important aspects of receptor localization and signaling to physiology and pathophysiology have been identified. In particular, extranuclear sex steroid receptors have been found in many normal cells and in epithelial tumors, where they enact signal transduction that impacts both nongenomic and genomic functions. Here, I focus on the progress made in understanding the roles of extranuclear estrogen receptors (ER) in physiology and pathophysiology. Extranuclear ER serve as a model to selectively intervene with novel receptor reagents to prevent or limit disease progression. Recent novel mouse models and membrane ER-selective agonists also provide a better understanding of receptor pool cross-talk that results in the overall integrative actions of sex steroids.


2004 ◽  
Vol 106 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Masato ISHIZUKA ◽  
Masahito HATORI ◽  
Takashi SUZUKI ◽  
Yasuhiro MIKI ◽  
Andrew D. DARNEL ◽  
...  

Rheumatoid arthritis (RA) is a disease characterized primarily by chronic inflammatory synovitis and is well-known to be associated with significant sex differences in its prevalence and clinical features. Sex steroids have been proposed to be involved in the pathogenesis of RA, but details pertaining to the expression of sex steroid receptors in RA synovial tissue have yet to be fully characterized. In the present study, we examined oestrogen receptor (ER) α, ERβ, progesterone receptor (PR) and androgen receptor (AR) mRNA expression using real-time reverse transcriptase–PCR (RT-PCR) in eight female RA synovial tissues and six female synovial tissues without inflammation, and determined immunolocalization of ERα, ERβ, PR-A, PR-B and AR using immunohistochemistry in synovial tissues obtained from 22 RA patients. Real-time RT-PCR analysis demonstrated the expression of ER, PR and AR mRNAs in both RA and non-inflamed synovial tissues. Relative abundance of ER mRNAs was significantly higher in RA synovial tissue than non-inflamed synovial tissue (P<0.05). In addition, the relative ERα/ERβ mRNA expression ratio was significantly lower in RA than non-inflamed synovial tissue (RA, 2.34±1.60; and non-inflamed, 20.7±19.1; P<0.05). There were no significant differences in relative abundance of PR mRNA. Relative abundance of AR mRNA was significantly lower in RA (P<0.05). Immunoreactivity for ERα, ERβ, PR-B and AR was detected in the lining cells, inflammatory cells and fibroblasts in all the patients examined. The labelling indices for ERβ and PR-B were more abundant in both lining cells (ERβ, 54.2±12.2%; PR-B, 73.6±18.9%) and inflammatory cells (ERβ, 74.6±16.2%; PR-B, 75.9±16.1%) than in fibroblasts (ERβ, 36.5±15.6%; PR-B, 49.4±18.0%). Labelling indices for ERα and AR were significantly higher in lining cells (ERα, 14.4±8.6%; AR, 31.2±11.3%) and fibroblasts (ERα, 12.1±7.5%; AR, 20.1±9.6%) than those in inflammatory cells (ERα, 5.7±3.3%; AR, 9.2±4.4%). There were significant differences (P<0.05) in the labelling indices for ERα, ERβ and PR-B between men and women under 50 years of age in fibroblasts of RA synovial tissues. These results indicate that sex steroid receptors are present in RA and non-inflamed synovial tissues, including inflammatory cells in RA, and suggest that sex steroids may play important roles in the regulation of inflammation of RA synovial tissue.


1996 ◽  
Vol 63 (6) ◽  
pp. 530-539 ◽  
Author(s):  
Gerardo G. Piroli ◽  
Claudia A. Grillo ◽  
Monica G. Ferrini ◽  
Victoria Lux-Lantos ◽  
Alejandro F. De Nicola

2014 ◽  
Vol 24 (12) ◽  
pp. 1450161 ◽  
Author(s):  
Ying Li ◽  
Zengrong Liu

MicroRNAs (miRNAs) interact with 3′untranslated region (UTR) elements of target genes to regulate mRNA stability or translation, and play a crucial role in regulating many different biological processes. bantam, a conserved miRNA, is involved in several functions, such as regulating Drosophila growth and circadian rhythm. Recently, it has been discovered that bantam plays a crucial role in the core circadian pacemaker. In this paper, based on experimental observations, a detailed dynamical model of bantam-regulated circadian clock system is developed to show the post-transcriptional behaviors in the modulation of Drosophila circadian rhythm, in which the regulation of bantam is incorporated into a classical model. The dynamical behaviors of the model are consistent with the experimental observations, which shows that bantam is an important regulator of Drosophila circadian rhythm. The sensitivity analysis of parameters demonstrates that with the regulation of bantam the system is more sensitive to perturbations, indicating that bantam regulation makes it easier for the organism to modulate its period against the environmental perturbations. The effectiveness in rescuing locomotor activity rhythms of mutated flies shows that bantam is necessary for strong and sustained rhythms. In addition, the biological mechanisms of bantam regulation are analyzed, which may help us more clearly understand Drosophila circadian rhythm regulated by other miRNAs.


Metabolism ◽  
2005 ◽  
Vol 54 (9) ◽  
pp. 1162-1167 ◽  
Author(s):  
Xin Huang ◽  
Marc R. Blackman ◽  
Karen Herreman ◽  
Katharine M. Pabst ◽  
S. Mitchell Harman ◽  
...  

1983 ◽  
Vol 19 ◽  
pp. 166
Author(s):  
J. Hassoun ◽  
P.M. Martin ◽  
R.P. Vigouroux ◽  
M. Toga ◽  
M. Moguilewsky ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document