TCDD receptor

Hayashi, S., et. al., Expression of Ah receptor (TCDD receptor) during human monocytic differentiation, Carcinogenesis. 16, 1403, 1995. 

Safe S, Bandiera S, Sawyer T, et al. 1985. Effects of structure on binding to the 2,3,7,8-TCDD receptor protein and AHH induction-halogentated biphenyls. Environ Health Perspect 61 21-33. 

TCDD receptor) following a single intraperitoneal injection of 2,3,7,8-TCDD at doses of 50, 100, or 150 g/kg (Meyne et al. 1985). The samples were examined within 8-48 hours. The negative results may, however, have been due to the time-dependent detectability of chromosomal changes after CDD exposure reported earlier (Loprieno et al. 1982). 

Rannug U, Sjogren M, Rannug A, et al. 1991. Use of artificial intelligence in structure-affinity correlations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) receptor ligands. Carcinogenesis 12 2007-2015. 

S. Safe, S. Bandiera, T. Sawyer, B. Zmudzka, G. Mason, M. Romkes, M. A. Denomme, J. Sparling, A. B. Okey, and T. Fujita, Environ. Health Perspect., 61, 21 (1985). Effects of Structure on Binding to the 2,3,7,8-TCDD Receptor Protein and AHH Induction-Halogenated Biphenyls. 

Dibenzodioxins, including TCDD (dioxin), have been demonstrated to cause severe thymic atrophy with resulting effects on the immune system. The target seems to be the epithelial cells in the thymus, and it is interesting that thymus cells contain the TCDD receptor. Thymic atrophy correlates with the presence of this receptor, and other compounds which compete with TCDD for this receptor also cause thymic atrophy. The basis of the toxicity of TCDD to the thymus may be an effect on T-cell maturation and differentiation. The result of exposure of animals to TCDD is depressed antibody responses, increased susceptibility to infectious agents, and depressed T-cell function. In humans exposed to TCDD occupationally, decreased serum levels of some immunoglobulins and depressed lymphocyte responses to mitogens were reported. 

In addition to these reviews, Hansch analyses for binding affinities to the P-adrenergic receptor [738, 739], benzodiazepine receptor [740], tetrachlorodibenzodioxin (TCDD) receptor [741, 742], dopamine receptor [743], and estrogen receptor [744] as well as for... 

The remarkable potency of TCDD in eliciting its toxic effects in animals suggested the possible existence of a receptor for dioxin [167]. Biochemical and genetic evidence implicates the TCDD-receptor in the biological responses to dioxin-like compounds. Electrophoretic studies to evaluate the properties of specific proteins from inbred mouse strains reveal the existence of several forms of the TCDD-binding protein [168]. These observations imply the existence of multiple alleles at the Ah locus in mice [169], The biochemical properties of the different forms of the Ah receptor remain to be described. 

More subtle modes of action are also possible since the response to hormone receptor binding is complex and could be affected by chemical interference with receptor-related proteins, DNA methylation or histone acetylation. Dioxin (TCDD), for example, reduces the ability of the oestrogen-receptor complex to bind to the oestrogen response element of DNA, reducing gene transcription. ... 

The responsiveness of a tissue to a hormone depends on the density of receptors within its component cells. The number of receptors is determined by their rate of synthesis and catabolism, which is itself controlled by complex feedback mechanisms involving hormone action. Some chemicals are known to interfere with this regulation. For example, TCDD can act to increase or decrease the expression of the oestrogen receptor. ... 

There are even receptors that are known to become activated only due to interaction with a synthetic chemical, and no physiological agonist for such a receptor has been characterized. A model receptor in this class is the so-called Ah receptor complex that becomes activated subsequent to its exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxiu (TCDD). Activation of the. Ah receptor... 

Ah-receptor-mediated toxicity is particularly associated with the highly toxic compound 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), commonly referred to as dioxin. TCDD, and the concept of toxicity equivalency factors (TEFs) based on TCDDs, will be dealt with in Chapter 7. The main point to make at this juncture is that the toxicity of each individual coplanar congener in a mixture can be expressed in terms of a toxic equivalent calculated relative to the toxicity of dioxin. Summation of the toxic equivalents of the individual coplanar PCBs gives a measure of the toxicity of the whole mixture, as expressed through the Ah receptor mechanism. 

PCDDs and PCDEs, together with coplanar PCBs, can express Ah-receptor-mediated toxicity. TCDD (dioxin) is used as a reference compound in the determination of TEFs, which can be used to estimate TEQs (toxic equivalents) for residues of PHAHs found in wildlife samples. Biomarker assays for Ah-receptor-mediated toxicity have been based on the induction of P450 lAl. TEQs measured in field samples have sometimes been related to toxic effects upon individuals and associated ecological effects (e.g., reproductive success). 

Isolated liver membranes 0.17 or 0.79 pg 2,3,7,8-TCDD/kg FW Low dose caused 50% reduction in epidermal growth factor receptor high dose caused 50% increase in EROD activity 29... 

Atrophy of the thymus is a consistent finding in mammals poisoned by 2,3,7,8-TCDD, and suppression of thymus-dependent cellular immunity, particularly in young animals, may contribute to their death. Although the mechanisms of 2,3,7,8-TCDD toxicity are unclear, research areas include the role of thyroid hormones (Rozman et al. 1984) interference with plasma membrane functions (Matsumura 1983) alterations in ligand receptors (Vickers et al. 1985) the causes of hypophagia (reduced desire for food) and subsequent attempts to alter or reverse the pattern of weight loss (Courtney et al. 1978 Seefeld et al. 1984 Seefeld and Peterson 1984) and excretion kinetics of biotransformed metabolites (Koshakji et al. 1984). 

Group I planar PCBs are 10 times more toxic and 100 times more effective as inducers of cytochrome P-450c-dependent monooxygenase and 70 times more effective in competitively displacing 2,3,7,8-TCDD from a rat cytosol receptor protein than Group II planar PCBs (Table 24.4 ... 

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