scholarly journals Endocrine Disruption in Human Placenta: Expression of the Dioxin-Inducible Enzyme, Cyp1a1, Is Correlated With That of Thyroid Hormone-Regulated Genes

2014 ◽  
Vol 99 (12) ◽  
pp. E2735-E2743 ◽  
Author(s):  
Thomas L. Wadzinski ◽  
Katherine Geromini ◽  
Judy McKinley Brewer ◽  
Ruby Bansal ◽  
Nadia Abdelouahab ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Human Placenta ◽  
Placental Lactogen ◽  
Mrna Levels ◽  
Industrial Chemicals ◽  
Expression Of Genes ◽  
Inducible Enzyme ◽  
Cyp1a1 Expression ◽  
Cyp1a1 Mrna

Context: Thyroid hormone (TH) is essential for normal development; therefore, disruption of TH action by a number of industrial chemicals is critical to identify. Several chemicals including polychlorinated biphenyls are metabolized by the dioxin-inducible enzyme CYP1A1; some of their metabolites can interact with the TH receptor. In animals, this mechanism is reflected by a strong correlation between the expression of CYP1A1 mRNA and TH-regulated mRNAs. If this mechanism occurs in humans, we expect that CYP1A1 expression will be positively correlated with the expression of genes regulated by TH. Objective: The objective of the study was to test the hypothesis that CYP1A1 mRNA expression is correlated with TH-regulated mRNAs in human placenta. Methods: One hundred sixty-four placental samples from pregnancies with no thyroid disease were obtained from the GESTE study (Sherbrooke, Québec, Canada). Maternal and cord blood TH levels were measured at birth. The mRNA levels of CYP1A1 and placental TH receptor targets [placental lactogen (PL) and GH-V] were quantitated by quantitative PCR. Results: CYP1A1 mRNA abundance varied 5-fold across 132 placental samples that had detectable CYP1A1 mRNA. CYP1A1 mRNA was positively correlated with PL (r = 0.64; P < .0001) and GH-V (P < .0001, r = 0.62) mRNA. PL and GH-V mRNA were correlated with each other (r = 0.95; P < .0001), suggesting a common activator. The mRNAs not regulated by TH were not correlated with CYP1A1 expression. Conclusions: CYP1A1 mRNA expression is strongly associated with the expression of TH-regulated target gene mRNAs in human placenta, consistent with the endocrine-disrupting action of metabolites produced by CYP1A1.

Prepubertal male rats with high rates of germ-cell apoptosis present exacerbated rates of germ-cell apoptosis after serotonin depletion

2016 ◽  
Vol 28 (6) ◽  
pp. 806 ◽  
Author(s):  
Néstor Méndez Palacios ◽  
María Elena Ayala Escobar ◽  
Maximino Méndez Mendoza ◽  
Rubén Huerta Crispín ◽  
Octavio Guerrero Andrade ◽  
...  
Keyword(s):  
Gene Expression ◽  
Germ Cell ◽  
Mrna Expression ◽  
Cell Apoptosis ◽  
Differential Sensitivity ◽  
Male Rats ◽  
Mrna Levels ◽  
Germ Cell Apoptosis ◽  
Expression Of Genes ◽  
Prepubertal Rats

Male germ-cell apoptosis occurs naturally and can be increased by exposure to drugs and toxic chemicals. Individuals may have different rates of apoptosis and are likely to also exhibit differential sensitivity to outside influences. Previously, we reported that p-chloroamphetamine (pCA), a substance that inhibits serotonin synthesis, induced germ-cell apoptosis in prepubertal male rats. Here, we identified prepubertal rats with naturally high or low rates of germ-cell apoptosis and evaluated gene expression in both groups. Bax and Shbg mRNA levels were higher in rats with high rates of germ-cell apoptosis. Rats were then treated with pCA and the neuro-hormonal response and gene expression were evaluated. Treatment with pCA induced a reduction in serotonin concentrations but levels of sex hormones and gonadotrophins were not changed. Rats with initially high rates of germ-cell apoptosis had even higher rates of germ-cell apoptosis after treatment with pCA. In rats with high rates of germ-cell apoptosis Bax mRNA expression remained high after treatment with pCA. On the basis of category, an inverse relationship between mRNA expression of Bax and Bcl2, Bax and AR and Bax and Hsd3b2 was found. Here we provide evidence that innate levels of germ-cell apoptosis could be explained by the level of mRNA expression of genes involved with apoptosis and spermatogenesis.

Tumor VEGFA gene expression is associated with serum lactate dehydrogenase (LDH) levels and intratumoral mRNA expression of genes involved in glycolysis in patients with metastatic colorectal cancer (mCRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3530-3530 ◽  
Author(s):  
M. Azuma ◽  
M. M. Shi ◽  
C. J. Jacques ◽  
C. Barrett ◽  
K. D. Danenberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Lactate Dehydrogenase ◽  
Metastatic Colorectal Cancer ◽  
Mrna Expression ◽  
High Serum ◽  
Serum Lactate Dehydrogenase ◽  
Mrna Levels ◽  
Glut 1 ◽  
Expression Of Genes

3530 Background: It is well known that angiogenesis and glycolysis are regulated by hypoxic conditions. Recent clinical trials (CONFIRM1 and CONFIRM2) have shown that patients with mCRC with high serum LDH benefited from PTK787/ZK 222584, a VEGF receptor tyrosine kinase inhibitor. We tested the hypothesis that patients with high serum LDH have increased intratumoral expression of genes involved with hypoxia (hypoxia inducible factor (HIF1a and 2a) and lactate dehydrogenase A (LDHA) and glycolysis (glucose transporter 1 (Glut-1) and genes involved in angiogenesis such as vascular endothelial growth factor A (VEGFA) and neuropilin 1 (NRP1) in patients with mCRC. Methods: 78 formalin fixed paraffin embedded (FFPE) tumor samples from 36 patients (20 males, 16 females: Median age 59 years (range 29–84) with mCRC who underwent first line therapy (not from CONFIRM trials) were analyzed. In addition, tumor gene expression was correlated with serum LDH levels from the same group of patients. FFPE tissues were dissected using laser-captured microdissection and analyzed LDHA, VEGFA, HIF1a, HIF2a, Glut-1 and NRP1 mRNA expression using a quantitative real-time RT-PCR method. Gene expression values (relative mRNA levels) are expressed as ratios between the target gene and internal reference gene (beta-actin). Results: Spearman Rank Correlation Analysis of Associations Between serum LDH levels and Gene Expression values. Conclusions: Our results demonstrate that intratumoral gene expression of LDHA, HIF1a and HIF2a, Glut-1 and VEGFA are significantly correlated. Patients with high serum LDH have increased intratumoral gene expression of VEGFA. These results support the hypothesis that serum LDH levels may serve as a surrogate marker for activation of the HIF related genes in the tumor. These observations may explain the efficacy of PTK787 in metastatic colorectal cancer patients with high serum LDH levels. [Table: see text] [Table: see text]

scholarly journals Effects of LPS on the Secretion of Gonadotrophin Hormones and Expression of Genes in the Hypothalamus-Pituitary-Ovary (HPG) Axis in Laying Yangzhou Geese

Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2259
Author(s):  
Shijia Ying ◽  
Jialin Qin ◽  
Zichun Dai ◽  
Hao An ◽  
Huanxi Zhu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Time Course ◽  
Stocking Density ◽  
Gram Negative Bacteria ◽  
Mrna Levels ◽  
Hpg Axis ◽  
Expression Of Genes ◽  
Laying Performance ◽  
Gonadotrophin Releasing Hormone ◽  
Lps Treatment

Lipopolysaccharide (LPS) from gram-negative bacteria was found to be involved in the decrease in laying performance in goose flocks with high stocking density during summer months. LPS injection delayed the increase in the laying rate and altered hierarchical follicle morphology. While there is evidence that LPS exerts suppressive effects on goose reproduction, the time course effects of LPS on the hypothalamus-pituitary-ovary (HPG) axis remain elusive. In this study, we investigated the expression of genes in the HPG axis and the plasma gonadotrophin hormone concentrations in breeding geese at 0, 6, 12, 24, and 36 h after intravenous injection with LPS. The results showed that LPS treatment enhanced and suppressed expression of hypothalamic gonadotropin-inhibiting hormone (GnIH) and gonadotrophin-releasing hormone (GnRH) mRNA, respectively, and similar effects were observed on the mRNA expression of their receptors, GnIHR and GnRHR, in the pituitary. LPS treatment transiently increased follicle FSHβ mRNA expression at 12 h and exerted no significant effect on LHβ mRNA expression in the pituitary. Regardless of the expression of FSHβ and LHβ, plasma follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations were significantly increased during 24–36 h after LPS treatment. In the ovary, StAR and Cyp11a1 were mainly expressed in the granulosa layer (GL) of hierarchical follicles, while Cyp17a1 and Cyp19a1 were mainly expressed in white follicles (WFs) and yellowish follicles (YFs), and to a lesser extent in the theca layer (TL). After LPS treatment, the mRNA levels of Cyp11a1 in the GLs, Cyp17a1 in the WFs and TL, and Cyp19a1 in the WFs, YFs, and TL were significantly decreased. However, LPS treatment transiently upregulated StAR expression at 12 h. These results indicate that the exposure of laying geese to LPS may impair the HPG axis and disturb ovarian steroidogenesis. Our research provides new insights into reproductive dysfunction caused by LPS and the immune challenge in birds.

scholarly journals Thyroid hormone effects on androgen receptor messenger RNA expression in rat Sertoli and peritubular cells

1998 ◽  
Vol 156 (1) ◽  
pp. 43-50 ◽  
Author(s):  
NK Arambepola ◽  
D Bunick ◽  
PS Cooke
Keyword(s):  
Androgen Receptor ◽  
Thyroid Hormone ◽  
Mrna Expression ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Mrna Levels ◽  
Serum Free Medium ◽  
Free Medium ◽  
Serum Free ◽  
Peritubular Cells

Postnatal Sertoli cell maturation is characterized by a pronounced rise in androgen receptor (AR) expression, which increases several fold between birth and adulthood. Since both 3,3',5-triiodothyronine (T3) and FSH regulate Sertoli cell proliferation and differentiation, we have determined the effects of T3 and FSH on AR mRNA expression in cultured Sertoli cells from 5-day-old rats. These cultures contain 5-9% peritubular cells, which also express AR mRNA. To insure that the observed T3 responses did not result from peritubular cells, we examined T3 effects on AR mRNA expression in cultured 20-day-old Sertoli cells (which contain minimal peritubular contamination) and peritubular cells, and measured thyroid hormone receptor (TR) mRNA expression in both of these cell types. Sertoli cells from 5- and 20-day-old rat testes were grown in serum-free medium alone (controls) or with ovine FSH (100 ng/ml) and/or T3 (100 nM) for 4 days. Peritubular cells purified from 20-day-old rat testes were grown in serum-containing medium for 8 days. These cells were split 1:4, and grown an additional 8 days, the last 4 days in serum-free medium with or without T3. TR and AR mRNA levels in all cultures were determined by Northern blotting. AR mRNA levels in 5- and 20-day-old cultured Sertoli cells were significantly (P < 0.05) increased by both T3 and FSH alone. Furthermore, AR mRNA levels in Sertoli cells treated with T3 and FSH were greater than with either alone. TR mRNA expression was detected in cultured peritubular cells, but TR mRNA levels in these cells were only approximately 30% of that seen in 20-day-old cultured Sertoli cells. In contrast to Sertoli cells, T3 did not affect peritubular AR mRNA expression. These results indicate that T3 is an important regulator of the postnatal Sertoli cell AR mRNA increase. The additive effects of maximally stimulatory doses of FSH and T3 suggest these hormones work through different mechanisms to increase AR mRNA. TR mRNA expression in peritubular cells indicates these cells may be direct T3 targets, though the function of T3 in these cells is unknown.

scholarly journals Thyroid hormone receptor β2 is strongly up-regulated at all levels of the hypothalamo–pituitary–thyroidal axis during late embryogenesis in chicken

2007 ◽  
Vol 196 (3) ◽  
pp. 519-528 ◽  
Author(s):  
Sylvia V H Grommen ◽  
Lutgarde Arckens ◽  
Tim Theuwissen ◽  
Veerle M Darras ◽  
Bert De Groef
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Thyroid Hormone Receptor ◽  
Expression Patterns ◽  
Perinatal Period ◽  
Mrna Levels ◽  
Late Embryogenesis ◽  
Mrna Content ◽  
Hpt Axis

In this study, we tried to elucidate the changes in thyroid hormone (TH) receptor β2 (TRβ2) expression at the different levels of the hypothalamo–pituitary–thyroidal (HPT) axis during the last week of chicken embryonic development and hatching, a period characterized by an augmented activity of the HPT axis. We quantified TRβ2 mRNA in retina, pineal gland, and the major control levels of the HPT axis – brain, pituitary, and thyroid gland – at day 18 of incubation, and found the most abundant mRNA content in retina and pituitary. Thyroidal TRβ2 mRNA content increased dramatically between embryonic day 14 and 1 day post-hatch. In pituitary and hypothalamus, TRβ2 mRNA expression rose gradually, in parallel with increases in plasma thyroxine concentrations. Using in situ hybridization, we have demonstrated the presence of TRβ2 mRNA throughout the diencephalon and confirmed the elevation in TRβ2 mRNA expression in the hypophyseal thyrotropes. In vitro incubation with THs caused a down-regulation of TRβ2 mRNA levels in embryonic but not in post-hatch pituitaries. The observed expression patterns in pituitary and diencephalon may point to substantial changes in TRβ2-mediated TH feedback active during the perinatal period. The strong rise in thyroidal TRβ2 mRNA content could be indicative of an augmented modulation of thyroid development and/or function by THs toward and after hatching. Finally, THs proved to exert an age-dependent effect on pituitary TRβ2 mRNA expression.

scholarly journals Liver X Receptor-α Gene Expression Is Positively Regulated by Thyroid Hormone

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4667-4675 ◽  
Author(s):  
Koshi Hashimoto ◽  
Shunichi Matsumoto ◽  
Masanobu Yamada ◽  
Teturou Satoh ◽  
Masatomo Mori
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Mrna Expression ◽  
Cross Talk ◽  
Promoter Activity ◽  
Gene Promoter ◽  
Retinoid X Receptor ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Transcription Analysis

The nuclear oxysterol receptors, liver X receptors (LXRs), and thyroid hormone receptors (TRs) cross talk mutually in many aspects of transcription, sharing the same DNA binding site (direct repeat-4) with identical geometry and polarity. In the current study, we demonstrated that thyroid hormone (T3) up-regulated mouse LXR-α, but not LXR-β, mRNA expression in the liver and that cholesterol administration did not affect the LXR-α mRNA levels. Recently, several groups have reported that human LXR-α autoregulates its own gene promoter through binding to the LXR response element. Therefore, we examined whether TRs regulate the mouse LXR-α gene promoter activity. Luciferase assays showed that TR-β1 positively regulated the mouse LXR-α gene transcription. Analysis of serial deletion mutants of the promoter demonstrated that the positive regulation by TR-β1 was not observed in the −1240/+30-bp construct. EMSA(s) demonstrated that TR-β1 or retinoid X receptor-α did not bind to the region from −1300 to −1240 bp (site A), whereas chromatin-immunoprecipitation assays revealed that TR-β1 and retinoid X receptor-α were recruited to the site A, indicating the presence of intermediating protein between the nuclear receptors and DNA site. We also showed that human LXR-α gene expression and promoter activities were up-regulated by thyroid hormone. These data suggest that LXR-α mRNA expression is positively regulated by TR-β1 and thyroid hormone at the transcriptional level in mammals. This novel insight that thyroid hormone regulates LXR-α mRNA levels and promoter activity should shed light on a cross talk between LXR-α and TR-β1 as a new therapeutic target against dyslipidemia and atherosclerosis.

scholarly journals Differential Influence of Inositol Hexaphosphate on the Expression of Genes Encoding TGF-βIsoforms and Their Receptors in Intestinal Epithelial Cells Stimulated with Proinflammatory Agents

2013 ◽  
Vol 2013 ◽  
pp. 1-10
Author(s):  
Małgorzata Kapral ◽  
Joanna Wawszczyk ◽  
Stanisław Sośnicki ◽  
Ludmiła Węglarz
Keyword(s):  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Inositol Hexaphosphate ◽  
Inflammatory Conditions ◽  
Expression Of Genes ◽  
Genes Encoding

Transforming growth factorβ(TGF-β) is a multifunctional cytokine recognized as an important regulator of inflammatory responses. The effect of inositol hexaphosphate (IP6), a naturally occurring phytochemical, on the mRNA expression of TGF-β1, TGF-β2, TGF-β3 and TβRI, TβRII, and TβRIII receptors stimulated with bacterial lipopolysaccharides (Escherichia coliandSalmonella typhimurium) and IL-1βin intestinal cells Caco-2 for 3 and 12 h was investigated. Real-time qRT-PCR was used to validate mRNAs level of examined genes. Bacterial endotoxin promoted differential expression of TGF-βs and their receptors in a time-dependent manner. IL-1βupregulated mRNA levels of all TGF-βs and receptors at both 3 h and 12 h. IP6 elicited the opposed to LPS effect by increasing downregulated transcription of the examined genes and suppressing the expression of TGF-β1 at 12 h. IP6 counteracted the stimulatory effect of IL-1βon TGF-β1 and receptors expression by decreasing their mRNA levels. IP6 enhanced LPS- and IL-1β-stimulated mRNA expression of TGF-β2 and -β3. Based on these studies it may be concluded that IP6 present in the intestinal milieu may exert immunoregulatory effects and chemopreventive activity on colonic epithelium under inflammatory conditions or during microbe-induced infection/inflammation by modulating the expression of genes encoding TGF-βs and their receptors at transcriptional level.

scholarly journals TDCPP exposure affects the concentrations of thyroid hormones in zebrafish

2017 ◽  
Author(s):  
Jingxin Song
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Survival Rates ◽  
Mrna Levels ◽  
Expression Levels ◽  
Hormone Levels ◽  
Zebrafish Larvae ◽  
Thyroid Hormone Levels ◽  
Hpt Axis ◽  
Mrna Expression Levels

AbstractPrevious studies show that TDCPP may interrupt the thyroid endocrine system, however, the potential mechanisms involved in these processes were largely unknown. In this study, zebrafish embryos/larvae were exposed to TDCPP until 120 hpf, by which time most of the organs of the larvae have completed development. In this study, the effects of TDCPP on HPT axis were examined and the thyroid hormone levels were measured after TDCPP treatment. Zebrafish (Danio rerio) embryos were treated with a series concentration of TDCPP (10, 20, 40, 80, 160 and 320 μg/L) from 1 day post-fertilization (dpf) to 5 dpf. Exposure concentrations of TDCPP were determined based on the survival rates in each group. Total mRNA were isolated, first-strand cDNA were synthesis and qPCR were performed to detect the mRNA expression levels in hypothalamic-pituitary-thyroid (HPT) axis. The mRNA expression levels of genes involved in thyroid hormone homeostasis were increased in the TDCPP-treated larvae. The mRNA levels of genes involved in thyroid hormone synthesis were also increased in the embryos treated with TDCPP. Furthermore, exposure to TDCPP led to a dose-dependent effect on zebrafish development, including diminished hatching and survival rates, increased malformation. TDCPP treatment significantly reduced the T4 concentration in the 5 dpf zebrafish larvae, but increased the concentration of T3, suggesting the function of thyroid endocrine were interrupted in the TDCPP-exposed zebrafish. Taken together, these data indicated that TDCPP affected the thyroid hormone levels in the zebrafish larvae and could increased the mRNA expression levels of genes related to HPT axis, which further impaired the endocrine homeostasis and thyroid system.

149 THYROID HORMONE MARKER DEIODINASE 1 INDUCED BY 2,4,6-TRIBROMOPHENOL IN GH3 PITUITARY CELLS

2016 ◽  
Vol 28 (2) ◽  
pp. 204
Author(s):  
D. Lee ◽  
J.-U. Hwang ◽  
H. Y. Kang ◽  
E.-B. Jeung
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Thyroid Function ◽  
Gh3 Cells ◽  
Type I ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Phenol Red ◽  
Iodothyronine Deiodinase ◽  
Thyroid Receptor

Numerous medical materials and products in daily use are made of chemicals that are rarely found in the environment. Some of these chemicals may alter reproductive and thyroid function by interfering with endogenous estrogens, progesterone, and thyroid hormones. They are called endocrine-disrupting chemicals (EDC). To inhibit ignition and to reduce flammability of products, brominated flame retardants (BFR) are added to some products. 2,4,6-Tribromophenol (TBP) is an emerging EDC that is produced in some countries. To compare this emerging chemical to traditional EDC, we investigated this chemical in a rat pituitary cell line, GH3 cells. The GH3 cells were starved without phenol red for 7 days to eliminate any steroidogenic effect. Then, GH3 cells were incubated with 1–850 (thyroid receptor antagonist; 5.0 × 10–6 M) for 1 day before treatment with vehicle, triiodothyronine (T3; 1.0 × 10–9 M) and TBP (1.0 × 10–6 M) for 24 h, respectively. The TBP dose was determined from a previous pilot experiment using high, middle, and low doses. Each group of cells was prepared in triplicate and experiments were performed twice. Type I iodothyronine deiodinase (Dio1; thyromimetic marker), thyroid hormone receptor β, isoform 2 (Thrβ2), and growth hormone (Gh) were quantified by RT-qPCR. All data were analysed with a one-way ANOVA and Tukey’s studentized range test. Statistical analyses were performed with SAS software (SAS Institute Inc., Cary, NC, USA); P-values <0.05 were considered significant. RT-qPCR analysis was performed using the 2–ΔΔCT method employing 18S RNA (18S) as endogenous reference gene. Each gene of interest was normalized to vehicle. The mRNA expression of Dio1 and Gh were up-regulated via TBP treatment, but was lower than that of the T3-treated positive control. In pretreatments of 1–850 with T3 or TBP, mRNA levels of Dio1 were diminished through inhibition of thyroid receptor, but Gh mRNA level was not diminished. The mRNA expression of Thrβ2 was decreased in independent treatment of T3 or TBP, and no change in pretreatments of 1–850 with T3 or TBP. Although interfering effects of TBP on thyroid function have been partly studied, the dangers of TBP have been not yet obviously verified. In this study, we confirmed a thyromimetic effect of TBP mediated by thyroid receptor on GH3 cells.

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