Regulation of prostatic genes: role of androgens and zinc in gene expression

1986 ◽  
Vol 64 (6) ◽  
pp. 601-607 ◽  
Author(s):  
R. J. Matusik ◽  
C. Kreis ◽  
P. McNicol ◽  
R. Sweetland ◽  
C. Mullin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Peptide ◽  
Prostate Gland ◽  
Male Rats ◽  
Castration Resistant ◽  
Gene Transcripts ◽  
Specific Mrnas ◽  
Steady State Levels ◽  
Cloned Cdna

Gene expression in the rat dorsolateral prostate gland has been studied using cloned cDNA probes to the most abundant expressed mRNAs. One cDNA clone (pM-40) corresponds to two closely homologous mRNAs of about 880 nucleotides which code for two proteins of 23 and 21 kilodaltons (kDa). At least the 23-kDa protein contains a signal peptide. Another clone (pRWB) corresponds to a 1550-nucleotide mRNA which codes for a 52-kDa protein which also contains a signal peptide. The steady-state levels of these specific mRNAs increase in the dorsolateral prostate with sexual maturation. In castrated mature male rats, the M-40 mRNAs are inducible either by androgens or zinc, while the RWB mRNA is only responsive to androgens. In situ cDNA–mRNA hybridization histochemistry has been used to study the localization of the M-40 and RWB gene transcripts. Both M-40 and RWB mRNAs are most abundant in the epithelium of the lateral tip of the dorsolateral prostate. Following castration, the RWB mRNA decreases, while the M-40 mRNAs continue to be expressed in isolated areas of the epithelium. These castration-resistant cells maintain normal morphology in the absence of androgens.

scholarly journals Stress Modifies the Expression of Glucocorticoid-Responsive Genes by Acting at Epigenetic Levels in the Rat Prefrontal Cortex: Modulatory Activity of Lurasidone

2021 ◽  
Vol 22 (12) ◽  
pp. 6197
Author(s):  
Paola Brivio ◽  
Giulia Sbrini ◽  
Letizia Tarantini ◽  
Chiara Parravicini ◽  
Piotr Gruca ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chronic Stress ◽  
Chronic Mild Stress ◽  
Male Rats ◽  
Mild Stress ◽  
Experimental Conditions ◽  
Glucocorticoid Responsive Element ◽  
Responsive Element

Epigenetics is one of the mechanisms by which environmental factors can alter brain function and may contribute to central nervous system disorders. Alterations of DNA methylation and miRNA expression can induce long-lasting changes in neurobiological processes. Hence, we investigated the effect of chronic stress, by employing the chronic mild stress (CMS) and the chronic restraint stress protocol, in adult male rats, on the glucocorticoid receptor (GR) function. We focused on DNA methylation specifically in the proximity of the glucocorticoid responsive element (GRE) of the GR responsive genes Gadd45β, Sgk1, and Gilz and on selected miRNA targeting these genes. Moreover, we assessed the role of the antipsychotic lurasidone in modulating these alterations. Chronic stress downregulated Gadd45β and Gilz gene expression and lurasidone normalized the Gadd45β modification. At the epigenetic level, CMS induced hypermethylation of the GRE of Gadd45β gene, an effect prevented by lurasidone treatment. These stress-induced alterations were still present even after a period of rest from stress, indicating the enduring nature of such changes. However, the contribution of miRNA to the alterations in gene expression was moderate in our experimental conditions. Our results demonstrated that chronic stress mainly affects Gadd45β expression and methylation, effects that are prolonged over time, suggesting that stress leads to changes in DNA methylation that last also after the cessation of stress procedure, and that lurasidone is a modifier of such mechanisms.

Gene expression during mammalian oogenesis and early embryogenesis: quantification of three messenger RNAs abundant in fully grown mouse oocytes

Development ◽  
1989 ◽  
Vol 106 (2) ◽  
pp. 251-261 ◽  
Author(s):  
R.J. Roller ◽  
R.A. Kinloch ◽  
B.Y. Hiraoka ◽  
S.S. Li ◽  
P.M. Wassarman
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Early Embryogenesis ◽  
Messenger Rnas ◽  
Oocyte Growth ◽  
Mouse Oocytes ◽  
Mouse Tissues ◽  
Specific Mrnas ◽  
Steady State Levels ◽  
Ribonuclease Protection

Ribonuclease protection assays have been used to quantitatively assess changes in steady-state levels of specific mRNAs during oogenesis and early embryogenesis in mice. The mRNAs encode ZP3 (a glycoprotein that serves as a sperm receptor), LDH-B (heart-type lactate dehydrogenase), and MOM-1 (a protein of unknown function). MOM-1 and LDH-B are expressed in a variety of adult mouse tissues and midgestation embryos, whereas ZP3 expression is restricted completely to oocytes. All three mRNAs are expressed by growing mouse oocytes and accumulate to unusually high levels in fully grown oocytes as compared to somatic cells; 240,000, 200,000 and 74,000 copies mRNA per fully grown oocyte for ZP3, LDH-B and MOM-1, respectively. Steady-state levels of LDH-B and MOM-1 mRNA undergo a modest decline (approximately 20–40%) during ovulation when fully grown oocytes become unfertilized eggs and, in general, mirror the reported change in poly(A)+RNA levels during this period of development. On the other hand, the level of ZP3 mRNA declines dramatically (approximately 98%) during ovulation, from approximately 240,000 copies per oocyte to approximately 5000 copies per unfertilized egg, and ZP3 mRNA is undetectable in fertilized eggs (less than 1000 copies per fertilized egg). MOM-1 mRNA is expressed at relatively low levels in morulae (approximately 2000 copies per embryo) and blastocysts (approximately 5000 copies per embryo), whereas ZP3 mRNA remains undetectable (less than 1000 copies per embryo) at these stages of preimplantation development. These findings are discussed in the context of overall gene expression during oocyte growth, meiotic maturation and early embryogenesis in mice.

scholarly journals Inhibition of Growth Hormone Receptor Gene Expression by Saturated Fatty Acids: Role of Krüppel-Like Zinc Finger Factor, ZBP-89

2006 ◽  
Vol 20 (11) ◽  
pp. 2747-2760 ◽  
Author(s):  
Jamuna Thimmarayappa ◽  
Jinhong Sun ◽  
Laura E. Schultz ◽  
Prapai Dejkhamron ◽  
Chunxia Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Palmitic Acid ◽  
Receptor Gene ◽  
Inhibitory Effect ◽  
Cis Elements ◽  
Gh Receptor ◽  
Steady State Levels ◽  
Receptor Gene Expression

Abstract The expression and function of the GH receptor is critical for the actions of pituitary GH in the intact animal. The role of systemic factors in the reduced expression of the GH receptor and consequent GH insensitivity in pathological states such as sepsis, malnutrition, and poorly controlled diabetes mellitus is unclear. In the current study, we demonstrate that saturated (palmitic and myristic; 50 μm) fatty acids (FA) inhibit activity of the promoter of the major (L2) transcript of the GH receptor gene; unsaturated (oleic and linoleic) FA (200 μm) do not alter activity of the promoter. Comparable effects with palmitic acid and the nonmetabolizable analog bromo-palmitic acid, and failure of triacsin C to abrogate palmitic acids effects on GH receptor expression indicate that this effect is due to direct action(s) of FA. Palmitic acid, but not the unsaturated FA linoleic acid, decreased steady-state levels of endogenous L2 mRNA and GHR protein in 3T3-L1 preadipocytes. The effect of FA was localized to two cis elements located approximately 600 bp apart on the L2 promoter. EMSA and chromatin immunoprecipitation assays established that both these cis elements bind the Krüppel-type zinc finger transcription factor, ZBP-89. Ectopic expression of ZBP-89 amplified the inhibitory effect of FA on L2 promoter activity and on steady-state levels of endogenous L2 mRNA in 3T3-L1 preadipocytes. Mutational analyses of the two ZBP-89 binding sites revealed that both the sites are essential for palmitic acid’s inhibitory effect on the L2 promoter and for the enhancing effect of ZBP-89 on palmitic acid-induced inhibition of the L2 promoter. Our results establish a molecular basis for FA-induced inhibition of GH receptor gene expression in the pathogenesis of acquired GH insensitivity in pathological states such as poorly controlled diabetes mellitus and small for gestational age.

scholarly journals Cyclin F drives proliferation through SCF-dependent degradation of the retinoblastoma-like tumor suppressor p130/RBL2

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Taylor P Enrico ◽  
Wayne Stallaert ◽  
Elizaveta T Wick ◽  
Peter Ngoi ◽  
Xianxi Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Cell Cycle Gene ◽  
E3 Ligases ◽  
Gene Transcripts ◽  
Cyclin F ◽  
Cell Cycle Gene Expression

Cell cycle gene expression programs fuel proliferation and are universally dysregulated in cancer. The retinoblastoma (RB)-family of proteins, RB1, RBL1/p107 and RBL2/p130, coordinately repress cell cycle gene expression, inhibiting proliferation and suppressing tumorigenesis. Phosphorylation of RB-family proteins by cyclin dependent kinases is firmly established. Like phosphorylation, ubiquitination is essential to cell cycle control, and numerous proliferative regulators, tumor suppressors, and oncoproteins are ubiquitinated. However, little is known about the role of ubiquitin signaling in controlling RB-family proteins. A systems genetics analysis of CRISPR/Cas9 screens suggested the potential regulation of the RB-network by cyclin F, a substrate recognition receptor for the SCF family of E3 ligases. We demonstrate that RBL2/p130 is a direct substrate of SCFcyclin F. We map a cyclin F regulatory site to a flexible linker in the p130 pocket domain, and show that this site mediates binding, stability, and ubiquitination. Expression of a mutant version of p130, which cannot be ubiquitinated, severely impaired proliferative capacity and cell cycle progression. Consistently, we observed reduced expression of cell cycle gene transcripts, as well a reduced abundance of cell cycle proteins, analyzed by quantitative, iterative immunofluorescent imaging. These data suggest a key role for SCFcyclin F in the CDK-RB network and raise the possibility that aberrant p130 degradation could dysregulate the cell cycle in human cancers.

scholarly journals Histological modifications of the rat prostate following transection of somatic and autonomic nerves

2010 ◽  
Vol 82 (2) ◽  
pp. 397-404 ◽  
Author(s):  
Rosaura Diaz ◽  
Luis I. Garcia ◽  
Jose Locia ◽  
Milagros Silva ◽  
Sara Rodriguez ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Androgen Receptors ◽  
Prostate Gland ◽  
Male Rats ◽  
Autonomic Nerves ◽  
Neural Pathways ◽  
Cell Height ◽  
Afferent Nerves ◽  
Rat Prostate

It is known that hormones influence significantly the prostate tissue. However, we reported that mating induces an increase in androgen receptors, revealing a neural influence on the gland. These data suggested that somatic afferents (scrotal and genitofemoral nerves) and autonomic efferents (pelvic and hypogastric nerves) could regulate the structure of the prostate. Here we assessed the role of these nerves in maintaining the histology of the gland. Hence, afferent or efferent nerves of male rats were transected. Then, the ventral and dorsolateral regions of the prostate were processed for histology. Results showed that afferent transection affects prostate histology. The alveoli area decreased and increased in the ventral and dorsolateral prostate, respectively. The epithelial cell height increased in both regions. Efferent denervation produced dramatic changes in the prostate gland. The tissue lost its configuration, and the epithelium became scattered and almost vanished. Thus, afferent nerves are responsible for spinal processes pertaining to the trophic control of the prostate, activating its autonomic innervation. Hence, our data imply that innervation seems to be synergic with hormones for the healthy maintenance of the prostate. Thus, it is suggested that some prostate pathologies could be due to the failure of the autonomic neural pathways regulating the gland.

scholarly journals Epidermal growth factor inhibits intestinal NHE8 expression via reducing its basal transcription

2010 ◽  
Vol 299 (1) ◽  
pp. C51-C57 ◽  
Author(s):  
Hua Xu ◽  
Bo Zhang ◽  
Jing Li ◽  
Huacong Chen ◽  
James Tooley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mrna Expression ◽  
Cell Volume Regulation ◽  
Male Rats ◽  
Basal Transcription ◽  
Intestinal Maturation ◽  
Epidermal Growth

Sodium/hydrogen exchangers (NHEs) play a major role in Na+ absorption, cell volume regulation, and intracellular pH regulation. Of the nine identified mammalian NHEs, three (NHE2, NHE3, and NHE8) are localized on the apical membrane of epithelial cells in the small intestine and the kidney. Although the regulation of NHE2 and NHE3 expression has been extensively studied in the past decade, little is known about the regulation of NHE8 gene expression under physiological conditions. The current studies were performed to explore the role of epidermal growth factor (EGF) on NHE8 expression during intestinal maturation. Brush-border membrane vesicles (BBMV) were isolated from intestinal epithelia, and Western blot analysis was performed to determine NHE8 protein expression of sucking male rats treated with EGF. Real-time PCR was used to quantitate NHE8 mRNA expression in rats and Caco-2 cells. Human NHE8 promoter activity was characterized through transfection of Caco-2 cells. Gel mobility shift assays (GMSAs) were used to identify the promoter sequences and the transcriptional factors involved in EGF-mediated regulation. Our results showed that intestinal NHE8 mRNA expression was decreased in EGF-treated rats and Caco-2 cells, and NHE8 protein abundance was also decreased in EGF-treated rats. The activity of the human NHE8 gene promoter transfected in Caco-2 cells was also reduced by EGF treatment. This could be explained by reduced binding of transcription factor Sp3 on the NHE8 basal promoter region in the presence of EGF. Pretreatment with MEK1/2 inhibitor UO-126 could prevent EGF-mediated inhibition of NHE8 gene expression. In conclusion, this study showed that EGF inhibits NHE8 gene expression through reducing its basal transcription, suggesting an important role of EGF in regulating NHE expression during intestinal maturation.

scholarly journals Effect of Phoenix dactylifera pollen grains suspension in fertility of male rats.

2012 ◽  
Vol 9 (4) ◽  
pp. 575-583
Author(s):  
Baghdad Science Journal
Keyword(s):  
Body Weight ◽  
Prostate Gland ◽  
White Male ◽  
Pollen Grains ◽  
Phoenix Dactylifera ◽  
Male Rats ◽  
Reproductive Efficiency ◽  
Control Group ◽  
Hormonal Levels

This study was conducted to determine the role of Phoenix dactylifera pollen grains suspension in improving reproductive efficiency of white male rats. In thisexperiment 40 adult male rats were divided randomly into five equal groups and by following oral administration:the first group was given Phoenix d. pollen grains suspension with concentration 18 mg/kg body weight daily, the second group was given 54 mg/kg, the third group was given 108 mg/kg and fourth group 216 mg/kg body weight, and the last group which represented a control group administrated distilled water only, the administration continued for 40 consecutive days. The effect of Phoenix d. pollen grains in reproductive efficiency was evaluated depending on some parameters such as: weights of (testes, epididymes, seminal vesicle and prostate gland), Some testes parameters of epididymis sperms (sperms concentration, percentage of both sperms motility and viability and percentage of normal sperms).and measuring of some hormonal levels which affect on spermatogenesis like [Luteinizing hormone(LH), Follicle stimulating hormone(FSH) and Testosterone hormone(T)]. The results showed a significant increase (P

scholarly journals Dysregulation of splicing-related proteins in prostate cancer is controlled by FOXA1

2018 ◽  
Author(s):  
John G. Foster ◽  
Rebecca Arkell ◽  
Marco Del Giudice ◽  
Chinedu Anene ◽  
Andrea Lauria ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Patient Outcomes ◽  
Transcriptional Networks ◽  
Over Expression ◽  
Castration Resistant ◽  
Related Proteins ◽  
First Time

AbstractProstate cancer (PCa) is genomically driven by dysregulation of transcriptional networks involving the transcriptional factors (TFs) FOXA1, ERG, AR, and HOXB13. However, the role of these specific TFs in the regulation of alternative pre-mRNA splicing (AS), which is a proven therapeutic vulnerability for cancers driven by the TF MYC, is not described. Using transcriptomic datasets from PCa patients, we tested for an association between expression of FOXA1, ERG, AR, HOXB13, and MYC, and genes involved in AS - termed splicing-related proteins (SRPs), which have pleiotropic roles in RNA metabolism. We identified FOXA1 as the strongest predictor of dysregulated SRP gene expression, which was associated with PCa disease relapse after treatment. Subsequently, we selected a subset of FOXA1-binding and actively-transcribed SRP genes that phenocopy the FOXA1 dependency of PCa cells, and confirmed in vitro via knockdown and over-expression that FOXA1 regulates SRP gene expression. Finally, we demonstrated the persistence of a FOXA1-SRP gene association in treatment-relapsed castration-resistant PCa (CRPCa) patients. Our data demonstrate, for the first time, that FOXA1 controls dysregulated SRP gene expression, which is associated with poor PCa patient outcomes. Analogous to MYC-driven cancers, our findings implicate the therapeutic targeting of SRPs and AS in FOXA1-overexpressing PCa.

scholarly journals The role of local propolis extract against harmful effects of acrylamide on some male reproductive parameters in rats

2013 ◽  
Vol 12 (1) ◽  
pp. 87
Author(s):  
A. M. Ghazi
Keyword(s):  
Group Treatment ◽  
Prostate Gland ◽  
Sperm Concentration ◽  
Male Rats ◽  
Control Group ◽  
Albino Rats ◽  
Reproductive Parameters ◽  
Propolis Extract ◽  
Harmful Effects

Propolis is a natural resinous substance obtained from bee hives living on various plant sources. The present experiment was designed to investigate the protective role of ethanolic extract of local propolis against the possible reproductive harmful effects induced by acrylamide when administered orally in male rates. A total of Thirty sexually mature male albino rats were randomly divided equally into three different groups (n = 10) , the first one : served as normal control , the second group received acrylamide alone (150 mg / Kg BW) , the third group received acrylamide in same dose and treated with local propolis extract (200 mg / Kg BW) twice daily. Doses were given by drenching for four weeks. The result of study revealed that administration of acrylamide induced significant decrease in the sperm concentration , sperm motility , rate of viability and normal sperms as well as decrease in weights of testes , epidydemis ,prostate gland , seminal vesicles , serum testosterone , FSH , LH levels with significant increase in sperm abnormalities compared with control group. Treatment with local propolis extract improved the harmful effects of acrylamide on reproductive parameters in male rats toward the normal values.

scholarly journals Regulation of concentrations of mRNA for amylase, trypsinogen I and chymotrypsinogen B in rat pancreas by secretagogues

1986 ◽  
Vol 235 (1) ◽  
pp. 305-308 ◽  
Author(s):  
W Renaud ◽  
D Giorgi ◽  
J Iovanna ◽  
J C Dagorn
Keyword(s):  
Gene Expression ◽  
Translational Regulation ◽  
Protein Gene ◽  
Secretory Protein ◽  
Serine Proteinases ◽  
Rat Pancreas ◽  
Rna Transcripts ◽  
Specific Mrnas ◽  
Cloned Cdna

Regulation of pancreatic gene expression by the secretory stimulants cholecystokinin-pancreozymin, caerulein and pilocarpine was studied in the rat, by using cloned cDNA probes to quantify concentrations of specific mRNAs (amylase, trypsinogen I and chymotrypsinogen B). It is concluded that long-term pancreatic stimulation results in pre-translational regulation of secretory-protein gene expression, with a preferential accumulation of RNA transcripts encoding serine proteinases, compared with that for amylase.

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