scholarly journals Primary Generalized Glucocorticoid Resistance and Hypersensitivity Syndromes: A 2021 Update

2021 ◽  
Vol 22 (19) ◽  
pp. 10839
Author(s):  
Nicolas C. Nicolaides ◽  
Evangelia Charmandari
Keyword(s):  
Target Genes ◽  
Glucocorticoid Resistance ◽  
Cellular Biology ◽  
Short Term ◽  
Cognate Receptor ◽  
Glucocorticoid Signaling ◽  
Tremendous Progress ◽  
Pleiotropic Actions ◽  
Optimal Effect ◽  
Pituitary Adrenal Axis

Glucocorticoids are the final products of the neuroendocrine hypothalamic–pituitary—adrenal axis, and play an important role in the stress response to re-establish homeostasis when it is threatened, or perceived as threatened. These steroid hormones have pleiotropic actions through binding to their cognate receptor, the human glucocorticoid receptor, which functions as a ligand-bound transcription factor inducing or repressing the expression of a large number of target genes. To achieve homeostasis, glucocorticoid signaling should have an optimal effect on all tissues. Indeed, any inappropriate glucocorticoid effect in terms of quantity or quality has been associated with pathologic conditions, which are characterized by short-term or long-lasting detrimental effects. Two such conditions, the primary generalized glucocorticoid resistance and hypersensitivity syndromes, are discussed in this review article. Undoubtedly, the tremendous progress of structural, molecular, and cellular biology, in association with the continued progress of biotechnology, has led to a better and more in-depth understanding of these rare endocrinologic conditions, as well as more effective therapeutic management.

scholarly journals A Transcription Factor Pulse Can Prime Chromatin for Heritable Transcriptional Memory

2016 ◽  
Vol 37 (4) ◽  
Author(s):  
Aimee Iberg-Badeaux ◽  
Samuel Collombet ◽  
Benoit Laurent ◽  
Chris van Oevelen ◽  
Kuo-Kai Chin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Rna Polymerase Ii ◽  
Target Genes ◽  
Short Term Memory ◽  
Epigenetic Mechanism ◽  
Short Term ◽  
Term Memory ◽  
Pol Ii ◽  
Transcriptional Memory

ABSTRACT Short-term and long-term transcriptional memory is the phenomenon whereby the kinetics or magnitude of gene induction is enhanced following a prior induction period. Short-term memory persists within one cell generation or in postmitotic cells, while long-term memory can survive multiple rounds of cell division. We have developed a tissue culture model to study the epigenetic basis for long-term transcriptional memory (LTTM) and subsequently used this model to better understand the epigenetic mechanisms that enable heritable memory of temporary stimuli. We find that a pulse of transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) induces LTTM on a subset of target genes that survives nine cell divisions. The chromatin landscape at genes that acquire LTTM is more repressed than at those genes that do not exhibit memory, akin to a latent state. We show through chromatin immunoprecipitation (ChIP) and chemical inhibitor studies that RNA polymerase II (Pol II) elongation is important for establishing memory in this model but that Pol II itself is not retained as part of the memory mechanism. More generally, our work reveals that a transcription factor involved in lineage specification can induce LTTM and that failure to rerepress chromatin is one epigenetic mechanism underlying transcriptional memory.

Diverse signaling pathways in the cellular actions of insulin

1996 ◽  
Vol 270 (3) ◽  
pp. E375-E385 ◽  
Author(s):  
A. R. Saltiel
Keyword(s):  
Signal Transduction ◽  
Insulin Receptor ◽  
Cellular Growth ◽  
Lipid Homeostasis ◽  
Signal Transduction Pathways ◽  
Hormone Binding ◽  
Short Term ◽  
Paradoxical Effects ◽  
Glucose And Lipid Homeostasis ◽  
Pleiotropic Actions

Insulin is one of the most important regulators of glucose and lipid homeostasis. Many of its cellular actions are mediated by changes in protein phosphorylation. The consequences of these phosphorylation events extend from a series of different short-term metabolic actions to longer-term effects of the hormone on cellular growth and differentiation. Although the insulin receptor itself is a tyrosine kinase that is activated upon hormone binding, the ensuing changes in phosphorylation occur predominantly on serine and threonine residues. Moreover, insulin can simultaneously stimulate the phosphorylation of some proteins and the dephosphorylation of others. These paradoxical effects of insulin suggest that separate signal transduction pathways may emanate from the receptor itself to produce the pleiotropic actions of the hormone.

scholarly journals The nutrigenomic metabolite L‑carnitine directly modulates the activity and expression of nuclear receptors in adipocytes, liver and muscle cells

2019 ◽  
Author(s):  
Lorenz Förster ◽  
Dominic Indra ◽  
Reinhold Hofbauer
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Target Genes ◽  
Muscle Cells ◽  
Carnitine Deficiency ◽  
Mrna Levels ◽  
Carnitine Supplementation ◽  
Short Term ◽  
Protein Activity ◽  
Expression Levels

Abstract Background: L‑carnitine is an indispensable metabolite in eukaryotic cells, which facilitates transport of long‑chain fatty acids into the mitochondrial matrix for subsequent β-oxidation and helps to safeguard the acetyl-CoA level. Additionally, L‑carnitine has been proven to exert a nutrigenomic effect, modulating the expression of numerous target genes. However, the diverging time-dependent effects of short-term and extended L‑carnitine supplementation have not been investigated in more detail yet, especially in the interplay of adipocytes, liver and muscle cells. A cell culture model with conditions of L‑carnitine deficiency and supplementation for these cell types was established to investigate the effects of L‑carnitine on key nuclear receptors and their pathways. Results: L‑carnitine deficiency as well as L‑carnitine supplementation to hepatocytes modulated protein activity of multiple nuclear receptor pathways (RAR, RXR, VDR, PPAR, HNF4, ER, LXR). On the transcriptional level, short‑term L‑carnitine supplementation initially exerted an inhibitory effect on the steady state mRNA levels of PPAR‑α, PPAR‑δ, PPAR-γ, RAR‑β , LXR‑α and RXR‑α in adipocytes, liver and muscle cells. However, extended L‑carnitine supplementation for 24 and 48 hours led to a significant upregulation of PPAR‑α and PPAR‑δ , being key regulators of lipid catabolism, thereby promoting lipolysis and β-oxidation. In addition, significant differences in transcriptional modulation were found between adipocytes, liver and muscle cells. Extended L‑carnitine administration to hepatocytes also modulated mRNA expression levels of nuclear receptor target genes CYP2R1 , ALDH1A1 , HSD11B2 , OGT and HMGCR. Conclusions: These findings show a clear nutrigenomic effect of L‑carnitine on the protein activity and expression levels of selected nuclear receptors in different tissues, promoting lipolytic gene expression as well as decreasing transcription of adipogenic and insulin-resistance linked genes. Therefore L‑carnitine supplementation obviously is a promising strategy supporting established antihyperlipidemic therapies.

Susceptibility of reproduction in female pigs to impairment by stress and the role of the hypothalamo - pituitary - adrenal axis

2002 ◽  
Vol 14 (6) ◽  
pp. 377 ◽  
Author(s):  
A. I. Turner ◽  
P. H. Hemsworth ◽  
A. J. Tilbrook
Keyword(s):  
Acute Stress ◽  
Adrenocorticotrophic Hormone ◽  
Short Term ◽  
Corticotrophin Releasing Factor ◽  
Other Substances ◽  
Reproductive Processes ◽  
The Impact ◽  
Prolonged Stress ◽  
Pituitary Adrenal Axis

Although it is generally considered that stress can impair reproduction, we suggest that the impact of acute or repeated acute stress or acute or repeated acute elevations of cortisol are of little consequence in female pigs, even if these occur during the series of endocrine events that induce oestrus and ovulation. It is important to understand the impact of acute stress on reproduction because, in the intensive production of livestock, animals are often subjected to short-term challenges. There seems little doubt that reproduction in a proportion of female pigs is susceptible to impairment by severe and prolonged stress or the sustained elevation of cortisol but only when this continues for a substantial period. In female pigs, where reproduction is susceptible to impairment by severe prolonged stress, it is possible that the mediators of this suppression are cortisol, corticotrophin-releasing factor and vasopressin but, in pigs, there is evidence to suggest that adrenocorticotrophic hormone is not involved. Other substances secreted during stress may be involved but these are not considered in this review. It is possible that the mediators of stress act at any level of the hypothalamo–pituitary–ovarian axis. Although a variety of experimental manipulations have provided potential mediators and mechanisms for the stress-induced suppression of reproduction, these experimental manipulations rarely represented physiological circumstances so it is not clear if such mechanisms would be important in a physiological context. The precise mediators and mechanisms by which hormones released during stress may inhibit reproductive processes during severe prolonged stress are yet to be determined.

Effects of short-term dexamethasone treatment during pregnancy on the development of the immune system and the hypothalamo-pituitary adrenal axis in the rat

1995 ◽  
Vol 63 (2) ◽  
pp. 183-191 ◽  
Author(s):  
Joost M. Bakker ◽  
E.Donné Schmidt ◽  
Hilde Kroes ◽  
Annemieke Kavelaars ◽  
Cobi J. Heijnen ◽  
...  
Keyword(s):  
Immune System ◽  
Dexamethasone Treatment ◽  
Short Term ◽  
Adrenal Axis ◽  
Pituitary Adrenal Axis
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