English Journal

Nanostructured sensors containing immobilized nuclear receptors for thyroid hormone detection.

Bendo L, Casanova M, Figueira AC, Polikarpov I, Zucolotto V.AbstractThyroid hormone receptors (TRs) are members of the nuclear receptors (NRs) superfamily, being encoded by two genes: TRa and TRbeta. In this paper, the ligand-binding domain (LBD) of the TRbeta1 isoform was immobilized on the surface of nanostructured electrodes for TR detection. The platforms containing TRbeta1-LBD were applied to the detection of specific ligand agonists, including the natural hormones T3 (triiodothyronine) and T4 (thyroxine), and the synthetic agonists TRIAC (3,5,3'-triiodothyroacetic acid) and GC-1 [3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl phenoxy) acetic acid]. Detection was performed via impedance spectroscopy. The biosensors were capable of distinguishing between the thyroid hormones T3 and T4, and/or the analogues TRIAC and GC-1 at concentrations as low as 50 nM. The detection and separation of thyroid hormones and analogue ligands by impedance techniques represents an innovative tool in the field of nanomedicine because it allows the design of inexpensive devices for the rapid and real-time detection of distinct ligand/receptor systems.
Journal of biomedical nanotechnology.J Biomed Nanotechnol.2014 May;10(5):744-50.
Thyroid hormone receptors (TRs) are members of the nuclear receptors (NRs) superfamily, being encoded by two genes: TRa and TRbeta. In this paper, the ligand-binding domain (LBD) of the TRbeta1 isoform was immobilized on the surface of nanostructured electrodes for TR detection. The platforms contai
PMID 24734526

Thyroid Hormone Signaling In Vivo Requires a Balance between Coactivators and Corepressors.

Vella KR1, Ramadoss P, Costa-E-Sousa RH, Astapova I, Ye FD, Holtz KA, Harris JC, Hollenberg AN.Author information 1Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.AbstractResistance to thyroid hormone (RTH), a human syndrome, is characterized by high thyroid hormone (TH) and thyroid-stimulating hormone (TSH) levels. Mice with mutations in the thyroid hormone receptor beta (TRβ) gene that cannot bind steroid receptor coactivator 1 (SRC-1) and Src-1(-/-) mice both have phenotypes similar to that of RTH. Conversely, mice expressing a mutant nuclear corepressor 1 (Ncor1) allele that cannot interact with TRβ, termed NCoRΔID, have low TH levels and normal TSH. We hypothesized that Src-1(-/-) mice have RTH due to unopposed corepressor action. To test this, we crossed NCoRΔID and Src-1(-/-) mice to create mice deficient for coregulator action in all cell types. Remarkably, NCoR(ΔID/ΔID) Src-1(-/-) mice have normal TH and TSH levels and are triiodothryonine (T3) sensitive at the level of the pituitary. Although absence of SRC-1 prevented T3 activation of key hepatic gene targets, NCoR(ΔID/ΔID) Src-1(-/-) mice reacquired hepatic T3 sensitivity. Using in vivo chromatin immunoprecipitation assays (ChIP) for the related coactivator SRC-2, we found enhanced SRC-2 recruitment to TR-binding regions of genes in NCoR(ΔID/ΔID) Src-1(-/-) mice, suggesting that SRC-2 is responsible for T3 sensitivity in the absence of NCoR1 and SRC-1. Thus, T3 targets require a critical balance between NCoR1 and SRC-1. Furthermore, replacement of NCoR1 with NCoRΔID corrects RTH in Src-1(-/-) mice through increased SRC-2 recruitment to T3 target genes.
Molecular and cellular biology.Mol Cell Biol.2014 May;34(9):1564-75. doi: 10.1128/MCB.00129-14. Epub 2014 Feb 18.
Resistance to thyroid hormone (RTH), a human syndrome, is characterized by high thyroid hormone (TH) and thyroid-stimulating hormone (TSH) levels. Mice with mutations in the thyroid hormone receptor beta (TRβ) gene that cannot bind steroid receptor coactivator 1 (SRC-1) and Src-1(-/-) mice both hav
PMID 24550004

Effects of waterborne cadmium on thyroid hormone levels and related gene expression in Chinese rare minnow larvae.

Li ZH1, Chen L2, Wu YH3, Li P4, Li YF2, Ni ZH5.Author information 1Key Laboratory of Freshwater Biodiversity Conservation (Ministry of Agriculture), Key Field Station for Fishery Resource and Environment in Upper-Middle Reaches of Yangtze River (Ministry of Agriculture), Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China; University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Research Institute of Fish Culture and Hydrobiology, Zátiší 728/II, 389 25 Vodňany, Czech Republic. Electronic address: zhihuali06@yahoo.com.2Key Laboratory of Freshwater Biodiversity Conservation (Ministry of Agriculture), Key Field Station for Fishery Resource and Environment in Upper-Middle Reaches of Yangtze River (Ministry of Agriculture), Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China.3Key Laboratory of Freshwater Biodiversity Conservation (Ministry of Agriculture), Key Field Station for Fishery Resource and Environment in Upper-Middle Reaches of Yangtze River (Ministry of Agriculture), Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China; Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, Chongqing 400715, China.4Key Laboratory of Freshwater Biodiversity Conservation (Ministry of Agriculture), Key Field Station for Fishery Resource and Environment in Upper-Middle Reaches of Yangtze River (Ministry of Agriculture), Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China; University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Research Institute of Fish Culture and Hydrobiology, Zátiší 728/II, 389 25 Vodňany, Czech Republic.5Key Laboratory of Freshwater Biodiversity Conservation (Ministry of Agriculture), Key Field Station for Fishery Resource and Environment in Upper-Middle Reaches of Yangtze River (Ministry of Agriculture), Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China. Electronic address: nizhaoh@yfi.ac.cn.AbstractCadmium is a heavy metal abundant in the environment that can induce endocrine disorder and toxicity in aquatic organisms at low levels. However, its effects on the thyroid system in fish are still unclear. In this study, the thyroid hormone (TH) levels and the expression profiles of genes related to hypothalamic- pituitary-thyroid (HPT) axis, including corticotropin-releasing hormone (crh), thyroid stimulating hormone beta (tshβ), solute carrier family 5 (sodium iodide symporter) member 5 (slc5a5), thyroglobulin (tg), thyroid hormone receptor alpha (trα) and thyroid hormone receptor beta (trβ), were determined in whole body of Chinese rare minnow (Gobiocypris rarus) larvae after exposure to different levels of Cd(2+) (0, 0.5 and 2.5mg/L) for 4days. And the 96-h lethal concentration of Cd(2+) on rare minnow larvae was determined as 2.59mg/L. The results showed that crh, slc5a5, tg and tshβ mRNA levels were significantly up-regulated in the larvae, but the gene expression of trα and trβ was down-regulated in a concentration-dependent manner. Besides, the THs levels decreased in the whole-body of fish, especially the thyroxine (T4) level. The above results indicated that Cd(2+) could alter gene expression in the HPT axis that might subsequently contribute to thyroid disruption.
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.Comp Biochem Physiol C Toxicol Pharmacol.2014 Apr;161:53-7. doi: 10.1016/j.cbpc.2014.02.001. Epub 2014 Feb 9.
Cadmium is a heavy metal abundant in the environment that can induce endocrine disorder and toxicity in aquatic organisms at low levels. However, its effects on the thyroid system in fish are still unclear. In this study, the thyroid hormone (TH) levels and the expression profiles of genes related t
PMID 24521933

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