Interaction of chlorinated phenols with thyroxine binding sites of human transthyretin, albumin and thyroid binding globulin

Berg, K.J. van den

doi:10.1016/0009-2797(90)90034-k

Cited by 126 publications

(67 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Metabolites and derivatives of PCBs, several brominated flame retardants and phenol compounds had remarkably stronger binding affinity than their parent compounds, indicating an important role for hydroxylation and halogenation in thyroid toxicity (118). In contrast to the interference with TTR, no environmental chemicals have been demonstrated to compete with THs for binding to TBG or albumin with significant strength (122,123).…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Environmental chemicals and thyroid function

Boas¹,

Feldt‐Rasmussen

Skakkebæk³

et al. 2006

eur j endocrinol

457

290

View full text Add to dashboard Cite

There is growing evidence that environmental chemicals can disrupt endocrine systems. Most evidence originates from studies on reproductive organs. However, there is also suspicion that thyroid homeostasis may be disrupted. Several groups of chemicals have potential for thyroid disruption. There is substantial evidence that polychlorinated biphenyls, dioxins and furans cause hypothyroidism in exposed animals and that environmentally occurring doses affect human thyroid homeostasis. Similarly, flame retardants reduce peripheral thyroid hormone (TH) levels in rodents, but human studies are scarce. Studies also indicate thyroid-disruptive properties of phthalates, but the effect of certain phthalates seems to be stimulative on TH production, contrary to most other groups of chemicals. Thyroid disruption may be caused by a variety of mechanisms, as different chemicals interfere with the hypothalamic -pituitary -thyroid axis at different levels. Mechanisms of action may involve the sodium-iodide symporter, thyroid peroxidase enzyme, receptors for THs or TSH, transport proteins or cellular uptake mechanisms. The peripheral metabolism of the THs can be affected through effects on iodothyronine deiodinases or hepatic enzymes. Even small changes in thyroid homeostasis may adversely affect human health, and especially fetal neurological development may be vulnerable. It is therefore urgent to clarify whether the animal data showing effects of chemicals on thyroid function can be extended to humans. European Journal of Endocrinology 154 599-611

show abstract

Section: Mechanisms Of Actionmentioning

confidence: 99%

Environmental chemicals and thyroid function

Boas¹,

Feldt‐Rasmussen

Skakkebæk³

et al. 2006

eur j endocrinol

457

290

View full text Add to dashboard Cite

show abstract

“…Indeed, several studies have established a causal relationship between PCB exposure and decreased T4 levels in rats [24] and monkeys [25].…”

Section: Polychlorinated Biphenylsmentioning

confidence: 99%

Endocrine disruptors and thyroid hormone physiology

Jugan

Lévi

Blondeau

2010

Biochemical Pharmacology

210

115

View full text Add to dashboard Cite

Endocrine disruptors are man-made chemicals that can disrupt the synthesis, circulating levels, and peripheral action of hormones. The disruption of sex hormones was subject of intensive research, but thyroid hormone synthesis and signaling are now also recognized as important targets of endocrine disruptors. The neurological development of mammals is largely dependent on normal thyroid hormone homeostasis, and it is likely to be particularly sensitive to disruption of the thyroid axis. Here, we survey the main thyroid-disrupting chemicals, such as polychlorinated biphenyls, perchlorates, and brominated flame retardants, that are characteristic disruptors of thyroid hormone homeostasis, and look at their suspected relationships to impaired development of the human central nervous system. The review then focuses on disrupting mechanisms known to be directly or indirectly related to the transcriptional activity of the thyroid hormone receptors.

show abstract

“…This type of interaction is not limited to OH-PCBs. Pentachlorophenol (PCP) binds with 2 times the affinity of T4 to TTR (15), indicating that other chlorinated phenolic compounds may also be interfering in thyroid hormone transport.…”

mentioning

confidence: 99%

“…Articles * Hydroxylated metabolites in Inuit whole blood hormone (15) and is responsible for 14-89% of the total phenolic comnpounds quantitated. Geyer et al (34) calculated the half-life of PCP as approximately 19 days and concluded that the German cohort's calculated intake of PCP exceeded the elimination rate and approximated a bioconcentration factor of 1.4 for blood.…”

mentioning

confidence: 99%

Analysis of hydroxylated metabolites of PCBs (OH-PCBs) and other chlorinated phenolic compounds in whole blood from Canadian inuit.

Sandau

Ayotte

Dewailly

et al. 2000

Environ Health Perspect

180

View full text Add to dashboard Cite

In this study, we identified the main hydroxylated polychlorinated biphenyls (OH-PCBs) and other chlorinated phenolic compounds and we determined their relative concentrations in whole blood from 13 male and 17 female Inuit from northern Quebec, Canada, and from a pooled whole blood sample from southern Quebec. We also determined concentrations of polychlorinated biphenyls (PCBs). Total OH-PCB concentrations were variable among the Inuit samples, ranging over 2 orders of magnitude (0.117-11.6 ng/g whole blood wet weight). These concentradions were equal to and up to 70 times those found for the southern Quebec pooled whole blood sample. Geometric mean concentrations of tota OH-PCBs were 1.73 and 1.01 nglg whole blood for Inuit men and women, respectively, and 0.161 nglg whole blood for the southern population pool. There are limited data available for comparison, but the levels of OH-PCBs in Imuit are higher thn those previously reported in the literature for other populations. There was a significant correlation (p < 0.005) between OH-PCBs and PCBs (r = 0.84) and both correlated significandy (p < 0.005) with age (r= 0.68 and 0.78, respectively). The ratio of OH-PCBs to PCBs was lower in Inuit (0.11) than in the southern Quebec pool (0.33). There is no apparent explanation for the difference. There was considerable variability in the congener pattem of the identified OH-PCBs. The main metabolite, 4-OH-CB109 (4-0H-2,3,3',4',5-pentachlorobiphenyl), constituted 12-62% of the total OH-PCBs in the samples. Pentachlorophenol (PCP) was the dominant phenolic compound in blood, constituting 46% (geometric mean) of the total quantitated chlorinated phenolic compounds. PCP concentrations in Imuit blood ranged from 0.558 to 7.77 ng/g on a wet weight basis. All but two Inuit samples had lower concentrations than the southern Quebec pool (6.29 ng/g). The possible role of OH-PCBs in mediating PCB-induced adverse effects needs to be investigated fiuther.

show abstract

Interaction of chlorinated phenols with thyroxine binding sites of human transthyretin, albumin and thyroid binding globulin

Cited by 126 publications

References 28 publications

Environmental chemicals and thyroid function

Environmental chemicals and thyroid function

Endocrine disruptors and thyroid hormone physiology

Analysis of hydroxylated metabolites of PCBs (OH-PCBs) and other chlorinated phenolic compounds in whole blood from Canadian inuit.

Contact Info

Product

Resources

About