The Hypothalamo–Pituitary–Adrenocortical Axis—An Overview of the Role of Glucocorticoids in the Pathophysiology of Endocrine Disorders and Perspectives for the Future

2011 ◽  
Vol 07 (01) ◽  
pp. 65
Author(s):  
Christopher D John ◽  
Julia C Buckingham ◽  
◽  
Keyword(s):  
Acute Stress ◽  
Subsequent Development ◽  
Endocrine Disorders ◽  
Adaptive Responses ◽  
Inhibitory Effects ◽  
Cellular Processes ◽  
Physiological Processes ◽  
Wear And Tear ◽  
Adaptive Processes

Glucocorticoids (GCs) are the end products of the hypothalamo–pituitary–adrenocortical axis (HPA) and, via activation of the ubiquitously expressed GC receptor, influence numerous physiological processes. GCs are also involved in the regulation of basal homeostasis as well as mediating adaptive responses to stress that act to restore homeostasis. This article discusses the various factors that are important in regulating plasma and intracellular GC concentrations and describes the genomic and non-genomic mechanisms used by GCs to influence cellular processes. We describe the concept of allostatic overload associated with chronic HPA activation and the subsequent development of tissue dysfunction and disease. While allostasis is associated with acute stress and a restoration of homeostasis, chronic stress is likely to induce allostatic overload owing to the sustained activation of adaptive processes. Increased wear and tear in GC-sensitive tissues can eventually lead to tissue dysfunction and disease. Chronic elevations in GCs can also induce dysfunction or disease associated with decreased tissue function owing to the prolonged inhibitory effects of GCs or the redistribution of metabolic resource away from physiological systems not involved in restoring homeostasis. Numerous endocrine-related disorders are associated with aberrant GC levels and in terms of pathophysiology may be linked with chronic tissue-specific alterations in GC actions.

The Hypothalamo–Pituitary–Adrenocortical Axis – An Overview of the Role of Glucocorticoids in the Pathophysiology of Endocrine Disorders and Perspectives for the Future

2010 ◽  
Vol 7 (1) ◽  
pp. 47
Author(s):  
Christopher D John ◽  
Julia C Buckingham ◽  
◽  
Keyword(s):  
Acute Stress ◽  
Subsequent Development ◽  
Endocrine Disorders ◽  
Adaptive Responses ◽  
Inhibitory Effects ◽  
Cellular Processes ◽  
Physiological Processes ◽  
Wear And Tear ◽  
Adaptive Processes

Glucocorticoids (GCs) are the end products of the hypothalamo–pituitary–adrenocortical axis (HPA) and, via activation of the ubiquitously expressed GC receptor, influence numerous physiological processes. GCs are also involved in the regulation of basal homeostasis as well as mediating adaptive responses to stress that act to restore homeostasis. This article discusses the various factors that are important in regulating plasma and intracellular GC concentrations and describes the genomic and non-genomic mechanisms used by GCs to influence cellular processes. We describe the concept of allostatic overload associated with chronic HPA activation and the subsequent development of tissue dysfunction and disease. While allostasis is associated with acute stress and a restoration of homeostasis, chronic stress is likely to induce allostatic overload owing to the sustained activation of adaptive processes. Increased wear and tear in GC-sensitive tissues can eventually lead to tissue dysfunction and disease. Chronic elevations in GCs can also induce dysfunction or disease associated with decreased tissue function owing to the prolonged inhibitory effects of GCs or the redistribution of metabolic resource away from physiological systems not involved in restoring homeostasis. Numerous endocrine-related disorders are associated with aberrant GC levels and in terms of pathophysiology may be linked with chronic tissue-specific alterations in GC actions.

scholarly journals Phosphodiesterase Activities in the Eye of Old and Young Rats in Normoxic, Hypoxic and Hyperoxic Atmospheres

2003 ◽  
Vol 1 (1) ◽  
pp. 25-32 ◽  
Author(s):  
G. Spoto ◽  
A. Contento ◽  
M. Di Nicola ◽  
G. Bianchi ◽  
C. Di Giulio ◽  
...  
Keyword(s):  
Cyclic Nucleotides ◽  
Biological Effects ◽  
Atmospheric Oxygen ◽  
Second Messengers ◽  
Camp Phosphodiesterase ◽  
Young Rats ◽  
Physiological Processes ◽  
Adaptive Processes ◽  
Old Rats

Phosphodiesterase activity was tested on homogenized eyes of young and old rats kept in hypoxic and hyperoxic conditions, with the aim of correlating any difference in PDE activity with aging and variations in atmospheric oxygen contents. The activities of the two enzymes, cAMP phosphodiesterase (cAMP-PDE) and cGMP phosphodiesterase (cGMP-PDE), were tested. Phosphodiesterases seem to be particularly susceptible to variations in oxygen tension, suggesting an important role of cyclic nucleotides in cellular adaptive processes. Particularly, cAMP-PDE activity increases lightly both in hypoxic and hyperoxic conditions in young and old rats. For cGMP-PDE activity of young rats, a similar behaviour to cAMP-PDE activity is observed with a similar increase in hypoxic and hyperoxic conditions respect to the control rats. Instead old rats seem to be quite insensible to hypoxia, while they show a fair increase in cGMP-PDE activity in the case of hyperoxia. The second messengers cAMP and cGMP play important roles in mediating the biological effects of a wide variety of first messengers. The intracellular levels of cyclic nucleotides depend upon rates of synthesis and degradation, actuated, respectively, by cyclases and phosphodiesterases (PDEs). Therefore, PDEs seem to play an important role in a wide variety of physiological processes.

scholarly journals The Role of Prokineticin 2 in Oxidative Stress and in Neuropathological Processes

2021 ◽  
Vol 12 ◽  
Author(s):  
Roberta Lattanzi ◽  
Cinzia Severini ◽  
Daniela Maftei ◽  
Luciano Saso ◽  
Aldo Badiani
Keyword(s):  
Pain Perception ◽  
G Protein Coupled Receptors ◽  
Cellular Processes ◽  
Prokineticin 2 ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
Double Function ◽  
The Central Nervous System ◽  
G Protein Coupled

The prokineticin (PK) family, prokineticin 1 and Bv8/prokineticin 2 (PROK2), initially discovered as regulators of gastrointestinal motility, interacts with two G protein-coupled receptors, PKR1 and PKR2, regulating important biological functions such as circadian rhythms, metabolism, angiogenesis, neurogenesis, muscle contractility, hematopoiesis, immune response, reproduction and pain perception. PROK2 and PK receptors, in particular PKR2, are widespread distributed in the central nervous system, in both neurons and glial cells. The PROK2 expression levels can be increased by a series of pathological insults, such as hypoxia, reactive oxygen species, beta amyloid and excitotoxic glutamate. This suggests that the PK system, participating in different cellular processes that cause neuronal death, can be a key mediator in neurological/neurodegenerative diseases. While many PROK2/PKRs effects in physiological processes have been documented, their role in neuropathological conditions is not fully clarified, since PROK2 can have a double function in the mechanisms underlying to neurodegeneration or neuroprotection. Here, we briefly outline the latest findings on the modulation of PROK2 and its cognate receptors following different pathological insults, providing information about their opposite neurotoxic and neuroprotective role in different pathological conditions.

Abstract P141: GYY4137, a H 2 S Donor, Normalizes miR-132 Targeted Sirt1 and Ace2 Expression to Improve Kidney Function in Hypertension

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Gregory Weber ◽  
Sathnur Pushpakumar ◽  
Utpal Sen
Keyword(s):  
Blood Flow ◽  
Kidney Function ◽  
Expression Patterns ◽  
Sirtuin 1 ◽  
Ang Ii ◽  
Cellular Processes ◽  
Physiological Processes ◽  
Epigenetic Gene Silencing ◽  
Increased Blood Flow

MicroRNAs regulate several physiological processes and are implicated in various pathologies, including hypertension. Previous work indicates miR-132 targets Sirtuin 1 (Sirt1), a histone deacetylase and regulator of epigenetic gene silencing in various cellular processes. Sirt1 is expressed in the kidney; however, its role in hypertensive kidney and whether it is regulated by physiological gaseous molecules, such as hydrogen sulfide (H 2 S), is not known. In this study, we sought to determine the role of miR-132 in regulating Sirt1, Ace2 and At1 in hypertensive kidney and whether H 2 S donor, GYY4137 (GYY), could reverse these effects and mitigates renal dysfunction. Wild-type mice were treated without or with Ang-II (1000 ng/Kg/Min) and GYY (133 μM) for 4 weeks. Quantitative PCR, Western blot, and immunofluorescence assays were performed. Increased expression levels of miR-132 in hypertensive mice (3.79 fold vs control) were reduced in mice receiving GYY treatment (2.43 fold vs control). Sirt1 expression was reduced (-1.15 fold) in Ang-II mice but was upregulated in GYY (1.25 fold) and Ang-II+GYY (1.9 fold) groups. A similar effect was seen with Sirt1 protein where the expression was increased in animals treated with GYY and Ang-II+GYY (1.16, 1.03 respectively) compared to Ang-II (0.47). Ace2 in Ang-II+GYY (0.45) was increased compared to Ang-II (0.17), while At1 was reduced (0.46) compared to Ang-II (0.86). Immunofluorescence showed decreased signal of Sirt1 in the glomerulus in Ang-II mice and increased At1 in the blood vessels surrounding the glomerulus, leading to constriction of renal artery, decreased blood flow, and kidney dysfunction. These effects were alleviated in mice treated with GYY. Our data suggests that upregulation of miR-132 in hypertensive kidney decreases Sirt1 and Ace2 expression, leading to increased Ang-II signaling through the At1 receptor and GYY supplementation reverses these expression patterns, leading to increased blood flow and kidney function.

scholarly journals Simultaneous Quantitation of Isoprenoid Pyrophosphates in Plasma and Cancer Cells Using LC-MS/MS

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3275 ◽  
Author(s):  
Yashpal Chhonker ◽  
Staci Haney ◽  
Veenu Bala ◽  
Sarah Holstein ◽  
Daryl Murry
Keyword(s):  
Ammonium Hydroxide ◽  
Reversed Phase ◽  
Ion Source ◽  
Farnesyl Pyrophosphate ◽  
Ionization Source ◽  
Limit Of Quantification ◽  
Cellular Processes ◽  
Physiological Processes ◽  
Gradient Condition

Isoprenoids (IsoP) are an important class of molecules involved in many different cellular processes including cholesterol synthesis. We have developed a sensitive and specific LC-MS/MS method for the quantitation of three key IsoPs in bio-matrices, geranyl pyrophosphate (GPP), farnesyl pyrophosphate (FPP), and geranylgeranyl pyrophosphate (GGPP). LC-MS/MS analysis was performed using a Nexera UPLC System connected to a LCMS-8060 (Shimadzu Scientific Instruments, Columbia, MD) with a dual ion source. The electrospray ionization source was operated in the negative MRM mode. The chromatographic separation and detection of analytes was achieved on a reversed phase ACCQ-TAG Ultra C18 (1.7 µm, 100 mm × 2.1 mm I.D.) column. The mobile phase consisted of (1) a 10 mM ammonium carbonate with 0.1% ammonium hydroxide in water, and (2) a 0.1% ammonium hydroxide in acetonitrile/methanol (75/25). The flow rate was set to 0.25 mL/min in a gradient condition. The limit of quantification was 0.04 ng/mL for all analytes with a correlation coefficient (r2) of 0.998 or better and a total run time of 12 min. The inter- and intra-day accuracy (85–115%) precision (<15%), and recovery (40–90%) values met the acceptance criteria. The validated method was successfully applied to quantitate basal concentrations of GPP, FPP and GGPP in human plasma and in cultured cancer cell lines. Our LC-MS/MS method may be used for IsoP quantification in different bio-fluids and to further investigate the role of these compounds in various physiological processes.

scholarly journals Identification of Novel miRNAs and Their Target Genes in the Response to Abscisic Acid in Arabidopsis

2021 ◽  
Vol 22 (13) ◽  
pp. 7153
Author(s):  
Syed Muhammad Muntazir Mehdi ◽  
Sivakumar Krishnamoorthy ◽  
Michal Wojciech Szczesniak ◽  
Agnieszka Ludwików
Keyword(s):  
Target Genes ◽  
Differentially Expressed ◽  
Small Rna Sequencing ◽  
Plant Responses ◽  
Biological Processes ◽  
Adaptive Responses ◽  
Cellular Processes ◽  
Potential Target ◽  
Novel Mirna

miRNAs are involved in various biological processes, including adaptive responses to abiotic stress. To understand the role of miRNAs in the response to ABA, ABA-responsive miRNAs were identified by small RNA sequencing in wild-type Arabidopsis, as well as in abi1td, mkkk17, and mkkk18 mutants. We identified 10 novel miRNAs in WT after ABA treatment, while in abi1td, mkkk17, and mkkk18 mutants, three, seven, and nine known miRNAs, respectively, were differentially expressed after ABA treatment. One novel miRNA (miRn-8) was differentially expressed in the mkkk17 mutant. Potential target genes of the miRNA panel were identified using psRNATarget. Sequencing results were validated by quantitative RT-PCR of several known and novel miRNAs in all genotypes. Of the predicted targets of novel miRNAs, seven target genes of six novel miRNAs were further validated by 5′ RLM-RACE. Gene ontology analyses showed the potential target genes of ABA-responsive known and novel miRNAs to be involved in diverse cellular processes in plants, including development and stomatal movement. These outcomes suggest that a number of the identified miRNAs have crucial roles in plant responses to environmental stress, as well as in plant development, and might have common regulatory roles in the core ABA signaling pathway.

scholarly journals RFamide-Related Peptide Gene Is a Melatonin-Driven Photoperiodic Gene

Endocrinology ◽  
2007 ◽  
Vol 149 (3) ◽  
pp. 902-912 ◽  
Author(s):  
Florent G. Revel ◽  
Michel Saboureau ◽  
Paul Pévet ◽  
Valérie Simonneaux ◽  
Jens D. Mikkelsen
Keyword(s):  
Wistar Rat ◽  
Reproductive Activity ◽  
Inhibitory Effects ◽  
Related Peptide ◽  
Physiological Processes ◽  
Siberian Hamsters ◽  
Long Day ◽  
General Inhibitor ◽  
Peptide Gene

In seasonal species, various physiological processes including reproduction are organized by photoperiod via melatonin, but the mechanisms of melatonin action are still unknown. In birds, the peptide gonadotropin-inhibiting hormone (GnIH) has been shown to have inhibitory effects on reproductive activity and displays seasonal changes of expression. Here we present evidence in mammals that the gene orthologous to GnIH, the RFamide-related peptide (RFRP) gene, expressed in the mediobasal hypothalamus, is strongly regulated by the length of the photoperiod, via melatonin. The level of RFRP mRNA and the number of RFRP-immunoreactive cell bodies were reduced in sexually quiescent Syrian and Siberian hamsters acclimated to short-day photoperiod (SD) compared with sexually active animals maintained under long-day photoperiod (LD). This was contrasted in the laboratory Wistar rat, a non-photoperiodic breeder, in which no evidence for RFRP photoperiodic modulation was seen. In Syrian hamsters, the reduction of RFRP expression in SD was independent from secondary changes in gonadal steroids. By contrast, the photoperiodic variation of RFRP expression was abolished in pinealectomized hamsters, and injections of LD hamsters with melatonin for 60 d provoked inhibition of RFRP expression down to SD levels, indicating that the regulation is dependent on melatonin. Altogether, these results demonstrate that in these hamster species, the RFRP neurons are photoperiodically modulated via a melatonin-dependent process. These observations raise questions on the role of RFRP as a general inhibitor of reproduction and evoke new perspectives for understanding how melatonin controls seasonal processes via hypothalamic targets.

scholarly journals Connexin43 controls N-cadherin transcription during collective cell migration

2017 ◽  
Author(s):  
Maria Kotini ◽  
Elias H. Barriga ◽  
Jonathan Leslie ◽  
Marc Gentzel ◽  
Alexandra Schambony ◽  
...  
Keyword(s):  
Cell Migration ◽  
Gap Junctions ◽  
Neural Crest ◽  
Cancer Metastasis ◽  
Embryonic Cell ◽  
Collective Cell Migration ◽  
List Type ◽  
Cellular Processes ◽  
Physiological Processes

AbstractConnexins are the primary components of gap junctions, providing direct links between cells in many physiological processes, including cell migration and cancer metastasis. Exactly how cell migration is controlled by gap junctions remains a mystery. To shed light on this, we investigated the role of Connexin43 in collective cell migration during embryo development using the neural crest, an embryonic cell population whose migratory behavior has been likened to cancer invasion. We discovered that Connexin43 is required for contact inhibition of locomotion by directly regulating the transcription of N-cadherin. For this function, the Connexin43 carboxy tail interacts with Basic Transcription Factor 3, which mediates its translocation to the nucleus. Together, they bind to the n-cad promotor regulating n-cad transcription. Thus, we uncover an unexpected, gap junction-independent role for Connexin43 in collective migration that illustrates the possibility that connexins, in general, may be important for a wide variety of cellular processes that we are only beginning to understand.HighlightsCx43 regulates collective directional migration of neural crest cellsCx43 carboxy tail controls cell polarity via n-cad regulationCx43 carboxy tail localises at the nucleus and that depends on BTF3BTF3 and Cx43 carboxy tail directly interact to bind and regulate n-cad promoter activity

scholarly journals SELENIUM LEVELS IN PEDIATRIC PATIENTS WITH ENDOCRINE DISEASES: EVIDENCE FROM A SYSTEMATIC REVIEW

2021 ◽  
pp. 25
Author(s):  
Vladimir Vuković ◽  
Ljiljana Šaranac ◽  
Marko Jović ◽  
Bojko Bjelaković
Keyword(s):  
Systematic Review ◽  
Endocrine Disorders ◽  
Endocrine Diseases ◽  
Physiological Processes ◽  
Newcastle Ottawa Scale ◽  
Different Populations ◽  
Se Deficiency ◽  
Age Studies

Selenium (Se) is essential micronutrient involved in several physiological processes. In many regions around the world, a suboptimal intake of Se has been reported in several health conditions, also in pediatric age. Studies on association between Se level and diseases in children reported contrasting results. We took an aim to perform a systematic review of literature and provide evidence-based conclusion on the magnitude of Se deficit in endocrine diseases in children. PubMed, ISI WoS, and Scopus databases were searched to identify eligible studies, published until July 25, 2019. Methodological quality was assessed using Newcastle–Ottawa Scale. After careful selection, 13 eligible studies were included. Majority were conducted in Turkey (n=5) and Iran (n=5), and sample size varied from 61 to 628 children, with a mean (±SD) age of cases from 5.1±1.6 months up to 13.8±4.5 years. Eleven studies focused on different thyroid diseases, and two on children with type 1 diabetes mellitus (T1DM). In goitrous patients, Se level ranged from mean (±SD), 25.71±20.68 μg/L to 114.9±34.1 μg/L, while in patients with T1DM was 20.9±12.9 μg/mL and mean (95% CI)=58.4 μg/L (55.0–63.09). We may conclude that goiter and thyroid dysfunction are prominent signs of Se deficiency in children. Although deficiency of iodine and selenium are usually combined in some area, our systematic review showed that Se deficiency is important goitrogenic factor in school children. Further randomized controlled trials are needed to adequately explore the role of Se in endocrine disorders in children, across different populations and regions.

Stimuli-dependent cleavage of Dicer during apoptosis

2008 ◽  
Vol 412 (3) ◽  
pp. 527-534 ◽  
Author(s):  
Alexey A. Matskevich ◽  
Karin Moelling
Keyword(s):  
Acute Stress ◽  
Protein Kinase C Inhibitors ◽  
Physiological Processes ◽  
Individual Mirnas ◽  
Infected Cells ◽  
Pkc Protein Kinase C ◽  
Mirna Pathway ◽  
Factor Α ◽  
Late Stages

miRNAs (microRNAs) play important roles in diverse physiological processes, including stress response, apoptosis and carcinogenesis. Even though the role of individual miRNAs has been demonstrated, expression of proteins involved in miRNA production in response to acute stress or harmful agents has not been extensively investigated. Here, we have studied the role of Dicer, one of the central proteins of the miRNA processing machinery during apoptosis, and show that down-regulation of Dicer results in accelerated apoptosis of HeLa cells, triggered by TNFα (tumour necrosis factor α). We have also investigated the integrity of Dicer, and provide evidence that Dicer is a target for caspases during apoptosis. The cleavage of Dicer is stimulidependent and more pronounced when apoptosis is induced by PKC (protein kinase C) inhibitors, and can also be observed in HIV-1-infected cells at late stages of infection. Thus the apoptotic machinery may regulate the miRNA pathway by affecting individual proteins, such as Dicer.

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