scholarly journals Unexpected effects of metyrapone on corticosteroid receptor interaction with the genome and subsequent gene transcription in the hippocampus of male rats

2019 ◽  
Vol 32 (2) ◽  
Author(s):  
Clare L. M. Kennedy ◽  
Sylvia D. Carter ◽  
Karen R. Mifsud ◽  
Johannes M. H. M. Reul
Keyword(s):  
Gene Transcription ◽  
Male Rats ◽  
Receptor Interaction ◽  
Corticosteroid Receptor

Regulation of glucose transporter GLUT-4 and hexokinase II gene transcription by insulin and epinephrine

1997 ◽  
Vol 273 (4) ◽  
pp. E682-E687 ◽  
Author(s):  
Jared P. Jones ◽  
G. Lynis Dohm
Keyword(s):  
Skeletal Muscle ◽  
Gene Transcription ◽  
Glucose Transporter ◽  
Male Rats ◽  
Rat Skeletal Muscle ◽  
Hexokinase Ii ◽  
Epinephrine Infusion ◽  
Glut 4 ◽  
Gastrocnemius Muscles

Transport of glucose across the plasma membrane by GLUT-4 and subsequent phosphorylation of glucose by hexokinase II (HKII) constitute the first two steps of glucose utilization in skeletal muscle. This study was undertaken to determine whether epinephrine and/or insulin regulates in vivo GLUT-4 and HKII gene transcription in rat skeletal muscle. In the first experiment, adrenodemedullated male rats were fasted 24 h and killed in the control condition or after being infused for 1.5 h with epinephrine (30 μg/ml at 1.68 ml/h). In the second experiment, male rats were fasted 24 h and killed after being infused for 2.5 h at 1.68 ml/h with saline or glucose (625 mg/ml) or insulin (39.9 μg/ml) plus glucose (625 mg/ml). Nuclei were isolated from pooled quadriceps, tibialis anterior, and gastrocnemius muscles. Transcriptional run-on analysis indicated that epinephrine infusion decreased GLUT-4 and increased HKII transcription compared with fasted controls. Both glucose and insulin plus glucose infusion induced increases in GLUT-4 and HKII transcription of twofold and three- to fourfold, respectively, compared with saline-infused rats. In conclusion, epinephrine and insulin may regulate GLUT-4 and HKII genes at the level of transcription in rat skeletal muscle.

scholarly journals Regulation of glucose transporters GLUT-4 and GLUT-1 gene transcription in denervated skeletal muscle

1998 ◽  
Vol 84 (5) ◽  
pp. 1661-1666 ◽  
Author(s):  
Jared P. Jones ◽  
Edward B. Tapscott ◽  
Ann Louise Olson ◽  
Jeffrey E. Pessin ◽  
G. Lynis Dohm
Keyword(s):  
Skeletal Muscle ◽  
Gene Transcription ◽  
Male Rats ◽  
Mrna Levels ◽  
Rnase Protection ◽  
Glut 1 ◽  
Glut 4 ◽  
The Right ◽  
Gastrocnemius Muscles ◽  
Cat Gene

Because GLUT-4 expression is decreased whereas GLUT-1 expression is increased in denervated skeletal muscle, we examined the effects of denervation on GLUT-4 and GLUT-1 gene transcription. The right hindlimb skeletal muscle of male transgenic mice containing sequential truncations (2,400, 1,639, 1,154, and 730 bp) of the human GLUT-4 promoter linked to the chloramphenacol acyl transferase (CAT) gene was denervated, and the contralateral hindlimb was sham operated. RNase protection analysis revealed that after 72 h denervation decreased CAT mRNA and GLUT-4 mRNA levels 64–85%, respectively ( P < 0.05), in the gastrocnemius muscles. In contrast, denervation of the right hindlimb of male rats increased GLUT-1 gene transcription and GLUT-1 mRNA levels by 94 and 213%, respectively ( P < 0.05). In conclusion, GLUT-4 transcription is decreased but GLUT-1 transcription is increased in denervated skeletal muscle, suggesting that the effects of denervation on GLUT-4 and GLUT-1 expression are, in part, transcriptionally mediated. Furthermore, these data indicate that a DNA sequence regulated by denervation is located within 730 bp of the 5′-flanking promoter region of the human GLUT-4 gene.

IGF-I and serine protease inhibitor 2·1 nuclear transcript abundance in rat liver during protein restriction

1995 ◽  
Vol 145 (3) ◽  
pp. 397-407 ◽  
Author(s):  
J M Hayden ◽  
D S Straus
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Gene Transcription ◽  
Transcript Abundance ◽  
Serine Protease Inhibitor ◽  
Protein Restriction ◽  
Male Rats ◽  
Igf I ◽  
I Gene ◽  
Nuclear Transcript

Abstract Restriction of dietary protein consumption of young male rats results in decreased growth velocity and a reduction in the abundance of hepatic IGF-I mRNA. It is not known whether the reduction in IGF-I mRNA abundance in the liver of protein-restricted rats results from a decrease in IGF-I gene transcription. In the present study, three experiments were performed with 4-week-old male rats to examine the effect of protein restriction on IGF-I gene transcription in liver. In these experiments, we monitored IGF-I nuclear transcripts (pre-mRNA) within total cellular RNA using a ribonuclease protection assay. In the first experiment, a consistent decrease in IGF-I mRNA from animals fed isocaloric diets containing 20% (control), 12%, 8% and 4% protein (dietary effect, P<0·001) was not paralleled by a decrease (P>0·50) in IGF-I pre-mRNA. Two additional experiments examining the effect of 4% vs 20% protein diets yielded comparable results. Pooled results from these two studies (n=12/treatment) demonstrated that a 64% reduction (P<0·0001) in IGF-I mRNA abundance was not accompanied by a decrease in IGF-I pre-mRNA (1·17 vs 1·31 ±0·21 image density units for 4% and 20% protein treatments). Unlike IGF-I, the abundance of carbamyl phosphate synthetase-I (CPS-I) pre-mRNA and mRNA was comparably reduced (∼70%, P<0·001), indicating that the decrease in mRNA of this urea cycle enzyme during protein restriction occurs predominantly by a transcriptional mechanism. A common feature of all experiments was a pronounced variability in the expression of hepatic IGF-I pre-mRNA among animals, which was not diet specific. To test whether the variability in IGF-I gene transcription was correlated with variability in the transcription of another gene that is regulated by GH, we quantified the abundance of nuclear transcripts for the serine protease inhibitor 2·1 (SPI 2·1 gene. A positive association (r=0·81, P<0·0001) between SPI 2·1 and IGF-I nuclear transcripts was demonstrated. The correlation between IGF-I and SPI 21 transcripts was specific, because the quantity of IGF-I and CPS-I nuclear transcripts was not correlated in this study. Although transcription of the IGF-I and SPI 2·1 genes was similar, the abundance of SPI 21 mRNA was not altered by protein deprivation. In summary, these studies indicated that protein restriction does not substantially alter the mean quantity of IGF-I nuclear transcripts, suggesting that the decrease in IGF mRNA occurs predominantly by a post-transcriptional mechanism. In addition, nuclear transcript abundance of the IGF-I and SPI 21 genes varies in a co-ordinate manner, supporting the hypothesis that transcription of these genes responds rapidly to a common variable factor such as plasma GH. Journal of Endocrinology (1995) 145, 397–407

scholarly journals Using RNA-Seq to Explore the Hub Genes in the Trigeminal Root Entry Zone of Rats by Compression Injury

2021 ◽  
pp. E573-E581
Keyword(s):  
Animal Model ◽  
Male Rats ◽  
Receptor Interaction ◽  
Rna Seq ◽  
Compression Injury ◽  
Hub Genes ◽  
Entry Zone ◽  
Kegg Analysis ◽  
Root Entry Zone ◽  
Trigeminal Root

BACKGROUND: Mechanical compression on the trigeminal root entry zone (TREZ) by microvascular is the main etiology of primary trigeminal neuralgia (TN). OBJECTIVES: To study the pathogenesis of TN, hub genes screening in the TREZ of TN in an animal model was performed. STUDY DESIGN: A double blind, randomized study was designed in a controlled animal trial. SETTING: The research took place in the Laboratory of Clinical Applied Anatomy at the School of Basic Medical Science of Fujian Medical University. METHODS: Twelve male rats were randomly divided into a sham operation group and a TN animal model group. TN animal model was induced by chronic compression of trigeminal nerve root (CCT) operation. Gene expression in the TREZ were analyzed by RNA sequencing (RNA-Seq) technique. KEGG analysis, GO analysis, and PPI analysis were performed in the DEGs. Key signaling pathways analyzing by GSEA and the hub genes in the DEGs were also studied. Reverse transcription real-time polymerase chain reaction (RT-qPCR) was used to verify the RNA-Seq results. RESULTS: Transcriptome data showed that 352 genes up-regulated and 59 genes down-regulated in DEGs on post-operation day 21, after CCT operation in the TN group. KEGG analysis revealed that, “neuroactive ligand receptor interaction” and “cytokine cytokine receptor interaction” may be related to the pathogenesis of TN. GO analysis showed “regulation of signing receptor activity”, “chemokine activity”, and “carbohydrate binging” may be related to TN. The RT-qPCR results were consistent with the test results, indicating that the transcriptome sequencing results were reliable. LIMITATIONS: Although the incidence of TN in female rats was higher than in male rats, we only used male SD rats to establish the TN animal model, to avoid the effect of estrogen on experimental results. This study only presents some respects of RNA-Seq technique and, therefore, did not identify the DEGs at the protein level. The relationship between the DEGs at different levels shoud be done in the future. CONCLUSIONS: Based on the results of RNA-seq, this study discovered 6 hub genes in the TREZ that are closely related to the TN animal model, which provide a potential breakthrough point to explore the pathogenesis of TN. KEY WORDS: Animal model, compression injury, hub gene, rat, RNA-seq, transcriptome, trigeminal neuralgia, trigeminal root entry zone

scholarly journals Low dose effects of dichlorodiphenyltrichloroethane (DDT) on gene transcription and DNA methylation in the hypothalamus of young male rats: implication of hormesis-like effects

2009 ◽  
Vol 34 (5) ◽  
pp. 469-482 ◽  
Author(s):  
Yasufumi Shutoh ◽  
Makio Takeda ◽  
Ryoichi Ohtsuka ◽  
Atsuko Haishima ◽  
Satoru Yamaguchi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Transcription ◽  
Low Dose ◽  
Young Male ◽  
Male Rats ◽  
Dose Effects ◽  
Low Dose Effects

scholarly journals Distinct Alterations in Chromatin Organization of the Two IGF-I Promoters Precede Growth Hormone-Induced Activation of IGF-I Gene Transcription

2010 ◽  
Vol 24 (4) ◽  
pp. 779-789 ◽  
Author(s):  
Dennis J. Chia ◽  
Jennifer J. Young ◽  
April R. Mertens ◽  
Peter Rotwein
Keyword(s):  
Gene Transcription ◽  
Histone H3 ◽  
Male Rats ◽  
Open Chromatin ◽  
Preinitiation Complex ◽  
Rna Pol Ii ◽  
Pol Ii ◽  
Igf I ◽  
The Impact ◽  
I Gene

Abstract Many of the physiological actions of GH are mediated by IGF-I, a secreted 70-residue peptide whose gene expression is induced by GH in the liver and other tissues via mechanisms that remain incompletely characterized but depend on the transcription factor Stat5b. Here we investigate the chromatin landscape of the IGF-I gene in the liver of pituitary-deficient young adult male rats and assess the impact of a single systemic GH injection. Despite minimal ongoing transcription in the absence of GH, both IGF-I promoters appear to reside in open chromatin environments, at least as inferred from relatively high levels of acetylation of core histones H3 and H4 when compared with adjacent intergenic DNA and from enhanced trimethylation of histone H3 at lysine 4. This landscape of open chromatin may reflect maturation of the liver. Surprisingly, in the absence of hormone, IGF-I promoter 1 appears poised to be activated, as evidenced by the presence of the transcriptional coactivator p300 and recruitment of RNA polymerase (Pol) II into a preinitiation complex. By contrast, chromatin surrounding IGF-I promoter 2 is devoid of both p300 and RNA Pol II. Systemic GH treatment causes an approximately 15-fold increase in transcription from each IGF-I promoter within 60 min of hormone administration, leading to a sustained accumulation of IGF-I mRNA. The coordinated induction of both IGF-I promoters by GH is accompanied by hyperacetylation of histones H3 and H4 in promoter-associated chromatin, a decline in monomethylation at lysine 4 of histone H3, and recruitment of RNA Pol II to IGF-I promoter 2. We conclude that GH actions induce rapid and dramatic changes in hepatic chromatin at the IGF-I locus and activate IGF-I gene transcription in the liver by distinct promoter-specific mechanisms: at promoter 1, GH causes RNA Pol II to be released from a previously recruited paused preinitiation complex, whereas at promoter 2, hormone treatment facilitates recruitment and then activation of RNA Pol II to initiate transcription.

Transcription of the rat skeletal muscle hexokinase II gene is increased by acute exercise

1996 ◽  
Vol 81 (2) ◽  
pp. 789-793 ◽  
Author(s):  
R. M. O'Doherty ◽  
D. P. Bracy ◽  
D. K. Granner ◽  
D. H. Wasserman
Keyword(s):  
Gene Transcription ◽  
Acute Exercise ◽  
Recovery Period ◽  
Male Rats ◽  
Fiber Types ◽  
Hexokinase Ii ◽  
Alpha Tubulin ◽  
Tubulin Genes ◽  
Beta Actin ◽  
Single Bout

A single bout of acute exercise increases hexokinase (HK) II mRNA and enzyme activity [R. M. O'Doherty, D. P. Bracy, H. Osawa, D. H. Wasserman, and D. K. Granner. Am. J. Physiol. 266 (Endocrinol. Metab. 29): E171-E178, 1994]. The present study addresses the mechanism of the increase in HK II mRNA. Male rats undertook a single bout of treadmill exercise and were then killed immediately or after a predetermined recovery period. The gastrocnemius/plantaris muscle complex, composed of mixed fiber types, was excised; the nuclei were isolated; and HK I, HK II, beta-actin, and alpha-tubulin gene transcription rates were measured. Genomic DNA and plasmid DNA were used as positive and negative controls, respectively. Immediately after the cessation of 30, 45, or 90 min of exercise, HK II gene transcription rates were 1.3 +/- 0.3-,2.9 +/- 0.3-, and 4.0 +/- 0.6-fold, respectively, above those of sedentary controls. The increases after 45 and 90 min of exercise were statistically significant (P < 0.01). One hour after the cessation of 30 min of exercise, HK II gene transcription was significantly increased (1.40 +/- 0.03-fold; P < 0.05). At all time points, transcription of the HK I, beta-actin, and alpha-tubulin genes was unchanged. We conclude that the exercise-induced increase in HK II gene transcription appears to play a major role in the increase of HK II mRNA and activity.

Neurotrophic ACTH analogue promotes plasticity of type I corticosteroid receptor in brain of senescent male rats

1988 ◽  
Vol 9 ◽  
pp. 253-260 ◽  
Author(s):  
Johannes M.H.M. Reul ◽  
Jeroen A.D.M. Tonnaer ◽  
E. Ronald De Kloet
Keyword(s):  
Male Rats ◽  
Type I ◽  
Corticosteroid Receptor ◽  
Acth Analogue

scholarly journals Neonatal Estrogen Down-Regulates Prostatic Androgen Receptor through a Proteosome-Mediated Protein Degradation Pathway

Endocrinology ◽  
2003 ◽  
Vol 144 (11) ◽  
pp. 4841-4850 ◽  
Author(s):  
Carl Woodham ◽  
Lynn Birch ◽  
Gail S. Prins
Keyword(s):  
Androgen Receptor ◽  
Protein Degradation ◽  
Gene Transcription ◽  
Male Rats ◽  
Ventral Prostate ◽  
Severe Dysplasia ◽  
Mrna Levels ◽  
Down Regulation ◽  
Normal Prostate

Abstract Brief exposure of male rats to estrogens during the neonatal period interrupts normal prostate development, alters epithelial cell differentiation, and predisposes this gland to hyperplasia and severe dysplasia analogous to prostatic intraepithelial neoplasia (PIN) with aging. Previous work demonstrated that the reduced growth, secretory activity, and androgen sensitivity that are observed in the adult ventral lobe are a function of reduced androgen receptor (AR) levels. Down-regulation of AR protein was found to occur immediately following neonatal exposure to estradiol benzoate (EB) and persist through adulthood and aging, indicating a permanent imprint on the ability of the prostate to express normal AR levels. To determine the intracellular mechanism of AR down-regulation by estrogens, the present study examined the effect of neonatal EB on AR gene transcription, mRNA levels, protein translation, and protein degradation in the d 10 ventral prostate glands. Nuclear run-on assays showed no alteration in AR gene transcription following exposure to EB on d 1–5 compared with controls. In situ hybridization and quantitative (q) RT-PCR revealed no difference in mRNA levels in the stromal or epithelial cells in response to estrogen exposure which, taken together, indicate that estrogen down-regulation of AR is mediated at the posttranscriptional level. AR translation was assessed with an in vitro transcription-translation assay in the presence of prostatic lysates from oil and estrogen-exposed animals, and no treatment effect was noted. AR degradation was examined in an in vitro assay validated with adult intact and castrate prostates. Prostatic lysates from intact rats initiated AR degradation with a t1/2 of 2.31 h, whereas proteins from castrate rats accelerated AR degradation to a t1/2 of 1.34 h (P &lt; 0.001). Prostatic lysates from control d 10 prostates induced AR degradation with a t1/2 of 1.49 h, whereas estrogenized prostates increased AR degradation to a t1/2 of 1.11 h (P &lt; 0.001). Proteosome inhibitors MG132 and ALLnL were able to reverse AR degradation induced by prostatic lysates from adult intact and castrate rats as well as from developing and estrogenized prostates, indicating that AR degradation was mediated through the proteosome pathway. Furthermore, the proteosome-mediated AR degradation in the estrogenized d 10 prostate was associated with a marked suppression of Akt phosphorylation that has been linked to AR degradation in other systems. Taken together, the present data show that exposure to neonatal estrogens down-regulates AR protein levels in the ventral prostate gland by accelerating AR degradation, which is mediated through the proteosome pathway.

scholarly journals Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors α and β by coactivators and corepressors

2004 ◽  
Vol 33 (2) ◽  
pp. 387-410 ◽  
Author(s):  
C M Klinge ◽  
S C Jernigan ◽  
K A Mattingly ◽  
K E Risinger ◽  
J Zhang
Keyword(s):  
Estrogen Receptors ◽  
Gene Transcription ◽  
Dna Sequences ◽  
Mammalian Cells ◽  
Transcriptional Activity ◽  
Steroid Receptor ◽  
Receptor Interaction ◽  
Arginine Methyltransferase ◽  
Estrogen Response ◽  
Methyltransferase 1

One mechanism by which ligand-activated estrogen receptors α and β (ERα and ERβ) stimulate gene transcription is through direct ER interaction with specific DNA sequences, estrogen response elements (EREs). ERE-bound ER recruits coactivators that stimulate gene transcription. Binding of ER to natural and synthetic EREs with different nucleotide sequences alters ER binding affinity, conformation, and transcriptional activity, indicating that the ERE sequence is an allosteric effector of ER action. Here we tested the hypothesis that alterations in ER conformation induced by binding to different ERE sequences modulates ER interaction with coactivators and corepressors. CHO-K1 cells transfected with ERα or ERβ show ERE sequence-dependent differences in the functional interaction of ERα and ERβ with coactivators steroid receptor coativator 1 (SRC-1), SRC-2 (glucocorticoid receptor interacting protein 1 (GRIP1)), SRC-3 amplified in breast cancer 1 (AIB1) and ACTR, cyclic AMP binding protein (CBP), and steroid receptor RNA activator (SRA), corepressors nuclear receptor co-repressor (NCoR) and silencing mediator for retinoid and thyroid hormone recpetors (SMRT), and secondary coactivators coactivator associated arginine methyltransferase 1 (CARM1) and protein arginine methyltransferase 1 (PRMT1). We note both ligand-independent as well estradiol- and 4-hydroxytamoxifen-dependent differences in ER-coregulator activity. In vitro ER-ERE binding assays using receptor interaction domains of these coregulators failed to recapitulate the cell-based results, substantiating the importance of the full-length proteins in regulating ER activity. These data demonstrated that the ERE sequence impacts estradiol-and 4-hydroxytamoxifen-occupied ERα and ERβ interaction with coregulators as measured by transcriptional activity in mammalian cells.

Sign in / Sign up

Export Citation Format

Share Document