scholarly journals Nongenomic Steroid Action: Controversies, Questions, and Answers

2003 ◽  
Vol 83 (3) ◽  
pp. 965-1016 ◽  
Author(s):  
RALF M. LÖSEL ◽  
ELISABETH FALKENSTEIN ◽  
MARTIN FEURING ◽  
ARMIN SCHULTZ ◽  
HANNS-CHRISTIAN TILLMANN ◽  
...  

Lösel, Ralf M., Elisabeth Falkenstein, Martin Feuring, Armin Schultz, Hanns-Christian Tillmann, Karin Rossol-Haseroth, and Martin Wehling. Nongenomic Steroid Action: Controversies, Questions, and Answers. Physiol Rev 83: 965–1016, 2003; 10.1152/physrev.00003.2003.—Steroids may exert their action in living cells by several ways: 1) the well-known genomic pathway, involving hormone binding to cytosolic (classic) receptors and subsequent modulation of gene expression followed by protein synthesis. 2) Alternatively, pathways are operating that do not act on the genome, therefore indicating nongenomic action. Although it is comparatively easy to confirm the nongenomic nature of a particular phenomenon observed, e.g., by using inhibitors of transcription or translation, considerable controversy exists about the identity of receptors that mediate these responses. Many different approaches have been employed to answer this question, including pharmacology, knock-out animals, and numerous biochemical studies. Evidence is presented for and against both the participation of classic receptors, or proteins closely related to them, as well as for the involvement of yet poorly understood, novel membrane steroid receptors. In addition, clinical implications for a wide array of nongenomic steroid actions are outlined.

2012 ◽  
Vol 23 (16) ◽  
pp. 3133-3142 ◽  
Author(s):  
James R. LaFountain ◽  
Christopher S. Cohan ◽  
Rudolf Oldenbourg

We report on experiments directly in living cells that reveal the regulation of kinetochore function by tension. X and Y sex chromosomes in crane fly (Nephrotoma suturalis) spermatocytes exhibit an atypical segregation mechanism in which each univalent maintains K-fibers to both poles. During anaphase, each maintains a leading fiber (which shortens) to one pole and a trailing fiber (which elongates) to the other. We used this intriguing behavior to study the motile states that X-Y kinetochores are able to support during anaphase. We used a laser microbeam to either sever a univalent along the plane of sister chromatid cohesion or knock out one of a univalent's two kinetochores to release one or both from the resistive influence of its sister's K-fiber. Released kinetochores with attached chromosome arms moved poleward at rates at least two times faster than normal. Furthermore, fluorescent speckle microscopy revealed that detached kinetochores converted their functional state from reverse pac-man to pac-man motility as a consequence of their release from mechanical tension. We conclude that kinetochores can exhibit pac-man motility, even though their normal behavior is dominated by traction fiber mechanics. Unleashing of kinetochore motility through loss of resistive force is further evidence for the emerging model that kinetochores are subject to tension-sensitive regulation.


The transition chapter describes the physiological changes that occur during every newborn’s transition from intrauterine to extrauterine life. Understanding this complex and intensive process of adaptation in the human life cycle is essential for understanding ACoRN’s approach to stabilization. Transition is examined systemically—from respiratory, cardiovascular, neurobehavioural, feeding, glycemic, renal, hepatic, thermal, and immunological perspectives. Some aspects of transition occur at birth (e.g., the separation of the placenta, onset of breathing, and the switch from fetal to neonatal circulation). Cardiorespiratory, neurological, glycemic, and thermal adaptations occur within minutes, as extra-uterine life begins. Endocrine, metabolic, and immunological adaptations unfold over several hours and days. Signs and symptoms of problems during transition are discussed in ‘learning points’, along with clinical implications for stabilization. Review questions and answers are included.


2010 ◽  
Vol 162 (5) ◽  
pp. 825-830 ◽  
Author(s):  
Alexandra Wendler ◽  
Elisabetta Baldi ◽  
Brian J Harvey ◽  
Angel Nadal ◽  
Anthony Norman ◽  
...  

Steroids exert their actions through several pathways. The classical genomic pathway, which involves binding of steroids to receptors and subsequent modulation of gene expression, is well characterized. Besides this, rapid actions of steroids have been shown to exist. Since 30 years, research on rapid actions of steroids is an emerging field of science. Today, rapid effects of steroids are well established, and are shown to exist for every type of steroid. The classical steroid receptors have been shown to be involved in rapid actions, but there is also strong evidence that unrelated structures mediate these rapid effects. Despite increasing knowledge about the mechanisms and structures which mediate these actions, there is still no unanimous acceptance of this category. This article briefly reviews the history of the field including current controversies and challenges. It is not meant as a broad review of literature, but should increase the awareness of the endocrinology society for rapid responses to steroids. As members of the organizing committee of the VI International Meeting on Rapid Responses to Steroid Hormones 2009, we propose a research agenda focusing on the identification of new receptoral structures and the identification of mechanisms of actions at physiological steroid concentrations. Additionally, efforts for the propagation of translational studies, which should finally lead to clinical benefit in the area of rapid steroid action research, should be intensified.


PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e105204 ◽  
Author(s):  
Hatice Z. Nenseth ◽  
Xavier Dezitter ◽  
Martina Tesikova ◽  
Florian Mueller ◽  
Tove I. Klokk ◽  
...  

2018 ◽  
Vol 466 ◽  
pp. 51-72 ◽  
Author(s):  
Viroj Boonyaratanakornkit ◽  
Nalo Hamilton ◽  
Diana C. Márquez-Garbán ◽  
Prangwan Pateetin ◽  
Eileen M. McGowan ◽  
...  

2007 ◽  
Vol 177 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Martin E. van Royen ◽  
Sónia M. Cunha ◽  
Maartje C. Brink ◽  
Karin A. Mattern ◽  
Alex L. Nigg ◽  
...  

Steroid receptors regulate gene expression in a ligand-dependent manner by binding specific DNA sequences. Ligand binding also changes the conformation of the ligand binding domain (LBD), allowing interaction with coregulators via LxxLL motifs. Androgen receptors (ARs) preferentially interact with coregulators containing LxxLL-related FxxLF motifs. The AR is regulated at an extra level by interaction of an FQNLF motif in the N-terminal domain with the C-terminal LBD (N/C interaction). Although it is generally recognized that AR coregulator and N/C interactions are essential for transcription regulation, their spatiotemporal organization is largely unknown. We performed simultaneous fluorescence resonance energy transfer and fluorescence redistribution after photobleaching measurements in living cells expressing ARs double tagged with yellow and cyan fluorescent proteins. We provide evidence that AR N/C interactions occur predominantly when ARs are mobile, possibly to prevent unfavorable or untimely cofactor interactions. N/C interactions are largely lost when AR transiently binds to DNA, predominantly in foci partly overlapping transcription sites. AR coregulator interactions occur preferentially when ARs are bound to DNA.


2003 ◽  
Vol 21 ◽  
pp. S21-S24 ◽  
Author(s):  
John Chalmers ◽  
Harold P. Adams ◽  
Geoffrey A. Donnan ◽  
Kim Fox ◽  
Stephen MacMahon ◽  
...  

2021 ◽  
Vol 41 ◽  
pp. 05003
Author(s):  
Alfino Sebastian ◽  
Widya Wasityastuti ◽  
Dwi Aris Nugrahaningsih ◽  
Hevi Wihadmadyatami ◽  
Tutik Sri Wahyuni ◽  
...  

Metabolism syndrome has many negative impacts on human health. Various efforts and methods are attempted in the treatment of this disease. One of the methods used is CRISPR/Cas9 gene therapy. Re-testing of knock out cells using the CRISPR/Cas9 method is needed to evaluate its success. In conducting the test, the right medium is needed so that the results are optimal and can be evaluated properly. In this study, we optimized the medium for three types of cells (fibroblasts, myoblasts and macrophages) in high and low glucose medium to evaluate gene knockout results. The medium was modified by adding high concentrations of glucose and sodium. The results, in macrophage culture, giving variations in glucose concentration in low glucose medium gave a significantly different percentage of live cells between treatments, while the treatment with variations in glucose concentration in macrophages in high glucose medium and fibroblasts and myoblasts in high and low glucose medium did not show any difference in the percentage of living cells. In the treatment of various concentrations of natrium, macrophages, fibroblasts and myoblasts on high and low glucose medium all showed significantly different percentages of living cells. Therefore, DMEM low glucose medium is suitable as a medium for the treatment of high glucose and natrium induction in macrophage cells, but is not suitable for fibroblast and myoblast cells.


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