scholarly journals Corticosterone-induced negative feedback mechanisms within the hypothalamo–pituitary–adrenal axis of the chicken

2005 ◽  
Vol 185 (3) ◽  
pp. 383-391 ◽  
Author(s):  
Kristien Vandenborne ◽  
Bert De Groef ◽  
Sofie M E Geelissen ◽  
Eduard R Kühn ◽  
Veerle M Darras ◽  
...  
Keyword(s):  
Gene Expression ◽  
Negative Feedback ◽  
Feedback Inhibition ◽  
Mrna Levels ◽  
Hypothalamic Area ◽  
Adrenal Axis ◽  
Pomc Mrna ◽  
Pituitary Adrenal Axis

This paper reports the results of in vivo and in vitro experiments on the feedback effects of corticosterone on the hypothalamo–pituitary–adrenal axis in embryos at day 18 of incubation and in 9-day-old chickens. In vivo, a significant negative feedback was detected on the levels of corticotropin-releasing factor (CRF) precursor (proCRF) mRNA and on the plasma concentration of corticosterone, two hours after a single intravenous injection with 40 μg corticosterone. In contrast, the levels of CRF peptide in the hypothalamic area, the CRF receptor type 1 (CRF-R1) mRNA and pro-opiomelanocortin (POMC) mRNA levels in the pituitary were not affected by the in vivo administration of corticosterone. In vitro, incubation with 1 μM corticosterone did not affect the CRF-R1 mRNA levels in the pituitary, but significant feedback inhibition was observed on the POMC mRNA levels. These in vitro effects were the same at the two ages studied. The in vitro feedback effect on the proCRF gene expression, however, differed with age. In 9-day-old animals a decrease in gene expression was observed which was not detectable in embryonic tissue at day 18 of the ontogeny.

The Hypothalamic Melanocortin System Stimulates the Hypothalamo-Pituitary-Adrenal Axis in vitro and in vivo in Male Rats

2002 ◽  
Vol 75 (4) ◽  
pp. 209-216 ◽  
Author(s):  
Waljit S. Dhillo ◽  
Caroline J. Small ◽  
Leighton J. Seal ◽  
Min-Seon Kim ◽  
Sarah A. Stanley ◽  
...  
Keyword(s):  
Male Rats ◽  
Melanocortin System ◽  
Adrenal Axis ◽  
Pituitary Adrenal Axis

scholarly journals A role for thioredoxin-interacting protein (Txnip) in cellular creatine homeostasis

2013 ◽  
Vol 305 (2) ◽  
pp. E263-E270 ◽  
Author(s):  
Sevasti Zervou ◽  
Tanmoy Ray ◽  
Natasha Sahgal ◽  
Liam Sebag-Montefiore ◽  
Rebecca Cross ◽  
...  
Keyword(s):  
Feedback Inhibition ◽  
Global Gene Expression ◽  
Negative Regulator ◽  
Specific Response ◽  
Mrna Levels ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Creatine Uptake

Creatine is important for energy metabolism, yet excitable cells such as cardiomyocytes do not synthesize creatine and rely on uptake via a specific membrane creatine transporter (CrT; SLC6A8). This process is tightly controlled with downregulation of CrT upon continued exposure to high creatine via mechanisms that are poorly understood. Our aim was to identify candidate endogenous CrT inhibitors. In 3T3 cells overexpressing the CrT, creatine uptake plateaued at 3 h in response to 5 mM creatine but peaked 33% higher ( P < 0.01) in the presence of cycloheximide, suggesting CrT regulation depends on new protein synthesis. Global gene expression analysis identified thioredoxin-interacting protein (Txnip) as the only significantly upregulated gene (by 46%) under these conditions ( P = 0.036), subsequently verified independently at mRNA and protein levels. There was no change in Txnip expression with exposure to 5 mM taurine, confirming a specific response to creatine rather than osmotic stress. Small-interfering RNA against Txnip prevented Txnip upregulation in response to high creatine, maintained normal levels of creatine uptake, and prevented downregulation of CrT mRNA. These findings were relevant to the in vivo heart since creatine-deficient mice showed 39.71% lower levels of Txnip mRNA, whereas mice overexpressing the CrT had 57.6% higher Txnip mRNA levels and 28.7% higher protein expression compared with wild types (mean myocardial creatine concentration 124 and 74 nmol/mg protein, respectively). In conclusion, we have identified Txnip as a novel negative regulator of creatine levels in vitro and in vivo, responsible for mediating substrate feedback inhibition and a potential target for modulating creatine homeostasis.

6 GENE EXPRESSION ANALYSIS OF IN VIVO- AND IN VITRO-MATURED PORCINE METAPHASE II OOCYTES

2014 ◽  
Vol 26 (1) ◽  
pp. 117 ◽  
Author(s):  
L. Cox ◽  
G. Saunders ◽  
J. Stevens ◽  
S. C. Isom
Keyword(s):  
Gene Expression ◽  
Rna Degradation ◽  
Functional Gene ◽  
Gene Set Enrichment Analysis ◽  
Developmental Competence ◽  
Mrna Levels ◽  
Multiple Testing Correction ◽  
Metaphase Ii Oocytes

In vitro-matured (IVM) oocytes lack the same developmental competence as oocytes that are matured in vivo (IVV), yet no compelling explanation for this discrepancy has been provided at the molecular level. The aim of this study was to quantify and compare mRNA levels in IVM and IVV oocytes for genes from a wide variety of functional gene categories, including RNA degradation, pluripotency, epigenome modification, oocyte-specific, and apoptosis. Quantitative real-time PCR (qPCR) was used to evaluate the relative gene expression levels of 70 genes in each of 33 individual IVM oocytes from 4 different collection days and 29 individual IVV oocytes from 4 different donor animals. The qPCR data were analysed using ANOVA and significance was assigned at P < 0.05. After a multiple testing correction was applied, relative transcript abundances for 32 of the 70 genes tested were found to be significantly different (q < 0.05) between the IVM and IVV oocytes. Of these significantly different genes, 23 were higher in the IVM oocytes and only 9 were higher in the IVV oocytes. The 32 significantly differentially expressed genes were then evaluated in relation to their corresponding functional gene categories. Of particular interest, transcripts for 7/14 RNA degradation-related genes (CNOT3, DCP1A, DDX6, LSM1, PABPN1, PABPN1L, PARN) and 3/9 oocyte specific genes (BMP15, YBX2, H1FOO) were significantly more abundant in the IVM oocytes. In contrast, transcripts for 4/8 epigenetic related transcripts (ASH2l, DNMT1, EHMT2, EZH2), 2/2 apoptosis related genes (BCL2, XIAP), and 1/4 pluripotency factors (LIN28) were significantly more abundant in the IVV oocytes. Gene set enrichment analysis confirmed that, within the context of this experimental design, RNA degradation and chromatin remodelling pathways are significantly perturbed in IVM oocytes. We conclude that in vitro maturation has profound effects on transcript populations of metaphase-II oocytes, with most transcripts being higher in IVM oocytes. We expect that this data will lead to a better understanding of how we can improve the quality of oocytes that are matured in vitro as well as provide information to help to identify markers that could be indicative of oocyte quality.

scholarly journals DNA Hypermethylation Downregulates Telomerase Reverse Transcriptase (TERT) during H. pylori-Induced Chronic Inflammation

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Françoise I. Bussière ◽  
Valérie Michel ◽  
Julien Fernandes ◽  
Lionel Costa ◽  
Vania Camilo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reverse Transcriptase ◽  
Chronic Inflammation ◽  
Telomerase Activity ◽  
Telomerase Reverse Transcriptase ◽  
Mrna Levels ◽  
Dna Hypermethylation ◽  
H Pylori

Helicobacter pylori infection causes chronic gastritis and is the major risk factor of gastric cancer. H. pylori induces a chronic inflammation-producing reactive oxygen species (ROS) which is a source of chromosome instabilities and contributes to the development of malignancy. H. pylori also promotes DNA hypermethylation, known to dysregulate essential genes that maintain genetic stability. The maintenance of telomere length by telomerase is essential for chromosome integrity. Telomerase reverse transcriptase (TERT) is the catalytic component of telomerase activity and an important target during host-pathogen interaction. We aimed to investigate the consequences of H. pylori on the regulation of TERT gene expression and telomerase activity. In vitro, hTERT mRNA levels and telomerase activity were analysed in H. pylori-infected human gastric epithelial cells. In addition, C57BL/6 and INS-GAS mice were used to investigate the influence of H. pylori-induced inflammation on TERT levels. Our data demonstrated that, in vitro, H. pylori inhibits TERT gene expression and decreases the telomerase activity. The exposure of cells to lycopene, an antioxidant compound, restores TERT levels in infected cells, indicating that ROS are implicated in this downregulation. In vivo, fewer TERT-positive cells are observed in gastric tissues of infected mice compared to uninfected, more predominantly in the vicinity of large aggregates of lymphocytes, suggesting an inflammation-mediated regulation. Furthermore, H. pylori appears to downregulate TERT gene expression through DNA hypermethylation as shown by the restoration of TERT transcript levels in cells treated with 5′-azacytidine, an inhibitor of DNA methylation. This was confirmed in infected mice, by PCR-methylation assay of the TERT gene promoter. Our data unraveled a novel way for H. pylori to promote genome instabilities through the inhibition of TERT levels and telomerase activity. This mechanism could play an important role in the early steps of gastric carcinogenesis.

scholarly journals Beta2-adrenoceptor desensitization in non-pregnant estrogen-primed rat myometrium involves modulation of oxytocin receptor gene expression

1998 ◽  
Vol 20 (2) ◽  
pp. 261-270 ◽  
Author(s):  
T Engstrom ◽  
P Bratholm ◽  
H Vilhardt ◽  
NJ Christensen
Keyword(s):  
Gene Expression ◽  
Contractile Response ◽  
Receptor Gene ◽  
Mrna Levels ◽  
Oxytocin Receptor Gene ◽  
Pregnant Rat ◽  
Homologous Desensitization ◽  
Stimulation Of

The nona-peptide oxytocin (OT) induces contraction of the myometrium by interaction with specific plasma membrane associated OT receptors (OTR), whereas stimulation of beta2-adrenoceptors (beta2AR) causes relaxation. Homologous desensitization of the myometrium to both hormones has been described. However, a possible interaction between the two systems has not been investigated. In the present study, long-term in vivo treatment of non-pregnant estrogen-primed rats with isoproterenol decreased maximal relaxation of isolated uterine strips challenged with isoproterenol. Increased EC50 values of similarly treated animals suggest that the coupling between receptor occupancy and contractile response was impaired. Since beta2AR mRNA levels were left unchanged, we conclude that the homologous desensitization to beta2 stimulation is not due to changes in beta2AR gene expression. OT infusion did not alter beta2AR mRNA levels or isoproterenol-induced relaxation of isolated uterine strips. Treatment with OT had no effect on the amount of myometrial OTR mRNA. We have previously found that OT down-regulates OTR in the non-pregnant rat myometrium, but this therefore does not appear to take place at the level of mRNA production. Isoproterenol treatment resulted in a three-fold increase in OTR mRNA. This was accompanied by a 91% rise in OTR binding and an augmented contractile response of isolated uterine strips to OT, suggesting that the increased production of mRNA reflects formation of active receptors. Neither OTR affinity nor EC50 of in vitro strips was affected by isoproterenol treatment. We conclude that stimulation of beta2AR causes heterologous up-regulation of OTR in the non-pregnant estrogen-primed rat myometrium.

Effects of diabetes and recurrent hypoglycemia on the regulation of the sympathoadrenal system and hypothalamo-pituitary-adrenal axis

2005 ◽  
Vol 288 (2) ◽  
pp. E422-E429 ◽  
Author(s):  
Karen E. Inouye ◽  
Owen Chan ◽  
Jessica T. Y. Yue ◽  
Stephen G. Matthews ◽  
Mladen Vranic
Keyword(s):  
Diabetic Rats ◽  
Hyperinsulinemic Hypoglycemia ◽  
Mrna Levels ◽  
Sympathoadrenal System ◽  
Adrenal Axis ◽  
Basal Expression ◽  
Pomc Mrna ◽  
Recurrent Hypoglycemia ◽  
Pituitary Adrenal Axis ◽  
Th Mrna

Epinephrine, norepinephrine, and corticosterone responses to hypoglycemia are impaired in diabetic rats. Recurrent hypoglycemia further diminishes epinephrine responses. This study examined the sympathoadrenal system and hypothalamo-pituitary-adrenal axis for molecular adaptations underlying these defects. Groups were normal (N) and diabetic (D) rats and diabetic rats exposed to 4 days of 2 episodes/day of hyperinsulinemic hypoglycemia (D-hypo) or hyperinsulinemic hyperglycemia (D-hyper). D-hypo and D-hyper rats differentiated effects of hypoglycemia and hyperinsulinemia. Adrenal tyrosine hydroxylase (TH) mRNA was reduced ( P < 0.05 vs. N) 25% in all diabetic groups. Remarkably, mRNA for phenylethanolamine N-methyltransferase (PNMT), which converts norepinephrine to epinephrine, was reduced ( P < 0.05 vs. all) 40% only in D-hypo rats. Paradoxically, dopamine β-hydroxylase mRNA was elevated ( P < 0.05 vs. D, D-hyper) in D-hypo rats. Hippocampal mineralocorticoid receptor (MR) mRNA was increased ( P < 0.05 vs. N) in all diabetic groups. Hippocampal glucocorticoid receptor (GR), hypothalamic paraventricular nucleus (PVN) GR and corticotropin-releasing hormone (CRH), and pituitary GR and proopiomelanocortin (POMC) mRNA levels did not differ. We conclude that blunted corticosterone responses to hypoglycemia in diabetic rats are not due to altered basal expression of GR, CRH, and POMC in the hippocampus, PVN, and pituitary. The corticosterone defect also does not appear to be due to increased hippocampal MR, since we have reported normalized corticosterone responses in D-hypo and D-hyper rats. Furthermore, impaired epinephrine counterregulation in diabetes is associated with reduced adrenal TH mRNA, whereas the additional epinephrine defect after recurrent hypoglycemia is associated with decreases in both TH and PNMT mRNA.

scholarly journals Yeast GMP Kinase Mutants Constitutively Express AMP Biosynthesis Genes by Phenocopying a Hypoxanthine-Guanine Phosphoribosyltransferase Defect

Genetics ◽  
2000 ◽  
Vol 156 (3) ◽  
pp. 953-961
Author(s):  
Karine Lecoq ◽  
Manfred Konrad ◽  
Bertrand Daignan-Fornier
Keyword(s):  
Gene Expression ◽  
Vegetative Growth ◽  
Kinase Activity ◽  
Feedback Inhibition ◽  
Purine Base ◽  
Growth Defects ◽  
Hypoxanthine Guanine Phosphoribosyltransferase ◽  
Lines Of Evidence

Abstract We have characterized a new locus, BRA3, leading to deregulation of the yeast purine synthesis genes (ADE genes). We show that bra3 mutations are alleles of the GUK1 gene, which encodes GMP kinase. The bra3 mutants have a low GMP kinase activity, excrete purines in the medium, and show vegetative growth defects and resistance to purine base analogs. The bra3 locus also corresponds to the previously described pur5 locus. Several lines of evidence indicate that the decrease in GMP kinase activity in the bra3 mutants results in GMP accumulation and feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), encoded by the HPT1 gene. First, guk1 and hpt1 mutants share several phenotypes, such as adenine derepression, purine excretion, and 8-azaguanine resistance. Second, overexpression of HPT1 allows suppression of the deregulated phenotype of the guk1 mutants. Third, we show that purified yeast HGPRT is inhibited by GMP in vitro. Finally, incorporation of hypoxanthine into nucleotides is similarly diminished in hpt1 and guk1 mutants in vivo. We conclude that the decrease in GMP kinase activity in the guk1 mutants results in deregulation of the ADE gene expression by phenocopying a defect in HGPRT. The possible occurrence of a similar phenomenon in humans is discussed.

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