Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Effects of estradiol and growth hormone on liver transcriptome in hypothyroid-orquiectomized rats

ABSTRACT: E2 and GH are critical regulators of growth and intermediate metabolism in mammals. Hypothyroidism causes endocrine and metabolic disturbances in the liver with features that mimic deficiencies of E2 or GH signalling. In this work, we used the hypothyroid-orchiectomized (TXOX) adult rat model to evaluate the influence of E2 and GH on the liver in terms of global changes in gene expression. This study shows the changes in hepatic transcriptome that were provoked by E2 benzoate (50 ug/kg; sc; 5 days per week x 27 days), intermittent GH administration (0.3 mg/kg/day;sc injection divided into two daily injections x 7 days) or the combination of E2 plus GH in TXOX rats. E2 influenced the liver transcriptome, particularly genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, gender, and immune responses. E2 did not prevent the inhibitory effects of GH on urea and amino acid metabolism-related genes. Notably, the combination of E2 and GH caused deleterious effects on transcriptional immune response. These results highlight the role of E2 as a critical regulator of liver metabolism in mammals and provide insights into the functional interplay between E2 and GH in the liver. Groups=4; Biological replicates = 4 per group; Samples=16; Reference samples=TXOX group. Adult (3 months old) male Sprague-Dawley rats (n=4 per group) were used throughout these experiments. The generation of TXOX was performed by adding methimazole (MMI; 0.05%) to the drinking water for 5 weeks starting on postnatal day (PND) 59 until sacrifice on PND94. Two weeks after starting MMI administration, male rats were castrated (OX) to make TXOX rats. Four days after OX, we began treatment with E2 benzoate (TXOXE2) or vehicle (TXOX) to TXOX rats for 20 days followed for 7 days by either vehicle plus GH (TXOXGH) or by E2 plus GH (TXOXE2GH). Twenty-four hours (in the case of E2) or twelve hours (in the case of GH) after the last injection, the animals were killed by exsanguinations. Portions of the liver were snap frozen in liquid nitrogen and stored at -80C until processed for mRNA analysis.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Leandro Fernandez-Perez

PROVIDER: E-GEOD-50014 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Transcriptional profiling of rat liver comparing male rats with congenital hypothyrodism (CH) vs intact at adulhood. Here we studied how CH influences liver gene expression program in adulthood. Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology but its specific influence in liver is less understood. Here we studied how CH influences liver gene expression program in adulthood. Pregnant rats were given anti-thyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as a reduction in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, feed efficiency increased in CH and this was accompanied by significant catch-up growth. On PND80, significant reduction in body mass, tail length, and circulating IGF-I remained in CH rats. On the other hand, mRNA levels of known GH targeted genes were significantly up-regulated. Serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in expression for hepatic genes involved in lipid metabolism with an increased transcription of PPAR and reduced expression of genes involved in fatty acids and cholesterol uptake, cellular sterol efflux, triglycerides assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to hypothyroidism onset in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters, and to T3 replacement with enhanced activation of lipogenic transcriptional program. In summary, we provided in vivo evidence that neonatal hypothyroidism causes long-lasting effects on hepatic transcriptional program and tissue sensitivity to hormone treatment. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood. Two conditions CH vs INTACT male rats. Biological replicates: Four independent hybridizations: 4 controls (age-matched intact rats) vs 4 CH (male rats with congenital hypothyroidism) on postnatal day 80 for a total of four arrays. One replicate per array.

Project description:Insight into the mechanisms for the anaerobic metabolism of aromatic compounds by the hyperthermophilic archaeon Ferroglobus placidus is expected to improve understanding of the degradation of aromatics in hot (> 80 °C) environments and to identify enzymes that might have biotechnological applications. Analysis of the F. placidus genome revealed genes predicted to encode enzymes homologous to those previously identified as playing a role in benzoate and phenol metabolism in mesophilic bacteria. Surprisingly, F. placidus lacks genes for an ATP-independent class II benzoyl-CoA reductase found in all strictly anaerobic bacteria, but instead has two sets of genes for ATP-consuming class I benzoyl-CoA reductases, similar to those found in facultative bacteria. The lower portion of the benzoate degradation pathway appears to be more similar to that found in the phototroph Rhodopseudomonas palustris, than the pathway reported for all heterotrophic anaerobic benzoate degraders. Many of the genes predicted to be involved in benzoate metabolism were found in one of two gene clusters. Genes for a phenol carboxylation proceeding through a phenylphosphate intermediate and for conversion of p-hydroxybenzoate to benzoyl-CoA were identified in a single gene cluster. Analysis of transcript abundance with a whole-genome microarray and quantitative PCR demonstrated that most of the genes predicted to be involved in benzoate or phenol metabolism had higher transcript abundance during growth on those substrates versus growth on acetate. These results suggest that the general strategies for benzoate and phenol metabolism may be highly conserved between microorganisms living in moderate and hot environments, and that anaerobic metabolism of aromatic compounds might be analyzed in a wide range of environments with similar molecular targets. A four chip study using total RNA recovered from two separate cultures of Ferroglobus placidus DSM 10642 grown with 1 mM sodium benzoate (experimental condition) and two separate cultures of Ferroglobus placidus DSM 10642 grown on 10 mM acetate (control condition). Each chip measures the expression level of 2613 genes from Ferroglobus placidus DSM 10642 with nine 45-60-mer probe pairs (PM/MM) per gene, with three-fold technical redundancy.

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Effects of estradiol and growth hormone on liver transcriptome in hypothyroid-orquiectomized rats

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