Enhanced in vitro hepatic glucuronidation of thyroxine in rats following cutaneous application or ingestion of polychlorinated biphenyls

Bastomsky, C. H.; Murthy, P. V. N.

doi:10.1139/y76-004

Cited by 45 publications

(13 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…OH-PCBs bound to the estrogen receptor and transactivated the estrogen receptor to DNA binding and altered gene expression in in vitro reporter gene assays (9,10 (17). PCB mixtures are also capable of inducing T4 glucuronidation (18)(19)(20)(21). A negative correlation between plasma T4 levels and hepatic T4 UGT activity has been observed (17).…”

Section: Estrogen Receptor-mediated Effectsmentioning

confidence: 97%

“…Some reports indicate an increased TSH concomitant with a low T4 level in adult rats after exposure to PCBs (19,42,43); other reports, mainly from in utero exposure to PCBs, have not observed an effect on TSH despite severely depressed T4 levels (32). Reduced brain T4 levels (by 90%) were also observed in fetal rats following in utero exposure to Aroclor 1254 (32).…”

Section: Estrogen Receptor-mediated Effectsmentioning

confidence: 98%

See 1 more Smart Citation

Characterization of Potential Endocrine-Related Health Effects at Low-Dose Levels of Exposure to PCBs

Brouwer¹,

Longnecker²,

Birnbaum³

et al. 1999

Environmental Health Perspectives

View full text Add to dashboard Cite

This article addresses issues related to the characterization of endocrine-related health effects resulting from low-level exposures to polychlorinated biphenyls (PCBs). It is not intended to be a comprehensive review of the literature but reflects workshop discussions. "The Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels," workshop provided a forum to discuss the methods and data needed to improve risk assessments of endocrine disruptors. This article contains an overview of endocrine-related (estrogen and thyroid system) interactions and other low-dose effects of PCBs. The data set on endocrine effects includes results obtained from mechanistic methods/ and models (receptor based, metabolism based, and transport protein based), as well as from in vivo models, including studies with experimental animals and wildlife species. Other low-dose effects induced by PCBs, such as neurodevelopmental and reproductive effects and endocrine-sensitive tumors, have been evaluated with respect to a possible causative linkage with PCB-induced alterations in endocrine systems. In addition, studies of low-dose exposure and effects in human populations are presented and critically evaluated. A list of conclusions and recommendations is included.

show abstract

Section: Estrogen Receptor-mediated Effectsmentioning

confidence: 97%

Section: Estrogen Receptor-mediated Effectsmentioning

confidence: 98%

Characterization of Potential Endocrine-Related Health Effects at Low-Dose Levels of Exposure to PCBs

Brouwer¹,

Longnecker²,

Birnbaum³

et al. 1999

Environmental Health Perspectives

View full text Add to dashboard Cite

show abstract

“…The biliary excretion of thyroxine is increased several fold in rats treated with benzpyrene (29), 3-methylcholanthrene (6), polychlorinated biphenyl (5,17), and TCDD (4). This is in contrast to about a 50% increase in biliary excretion we observed in phenobarbital treated rats.…”

Section: Polycyclic Hydrocarbon-like Enzyme Inducersmentioning

confidence: 99%

The Significance of Hepatic Microsomal Enzyme Induction and Altered Thyroid Function in Rats: Implications for Thyroid Gland Neoplasia

1989

Toxicol Pathol

166

View full text Add to dashboard Cite

Hepatic microsomal enzymes play an important role in thyroid hormone homeostasis. Glucuronidation of thyroxine is the rate limiting step in the biliary excretion of thyroxine in the rat; the monodeiodinases are important in the conversion of T4 to T, and reverse T3 and subsequent deiodinations. Phenobarbital is known to affect thyroid function in rats due to an alteration of hormone disposition. We have further characterized these effects and have demonstrated that phenobarbital increases the biliary excretion of thyroxine glucuronide primarily as a result of an induction of hepatic thyroxine glucuronyltransferase. Studies on the mode of action for phenobarbital promotion of thyroid follicular neoplasia were conducted using an initiation-promotion model established by Hiasa et a1 (35). In this model, we demonstrated that supplemental administration of thyroxine blocked the promoting effect of phenobarbital and furthermore, using various dosages of thyroxine, we observed that the tumor promoting effect of phenobarbital was directly proportional to the level of plasma TSH. The results of these studies support the hypothesis that the the tumor promoting effect of phenobarbital in the thyroid gland is mediated via increased secretion of pituitary TSH as a compensatory response to the known effects of phenobarbital on peripheral thyroid hormone disposition. Since a number of microsomal enzyme inducing agents have increased the incidence of thyroid follicular neoplasia in rat carcinogenicity studies, thyroid function should be assessed and a secondary mechanism of hormone imbalance should be considered in the interpretation of the significance of these findings in rodents.

show abstract

“…The diseaseproducing capability of these compounds has been well-documented and includes alterations in reproduction, growth, and development, amongst others. Some of these changes may be related to the finding that exposure to PCB causes a significant reduction in serum levels of thyroid hormones due to alterations in thyroid structure, in addition to the well-known induction of hepatic UDP-glucuronyl transferase and increased secretion of thyroxineglucuronide in the bile (5)(6)(7)(8).…”

Section: Polychlorinated Biphenyls (Pcb)mentioning

confidence: 99%

The Effects of Xenobiotics on the Structure and Function of Thyroid Follicular and C-Cells

1989

View full text Add to dashboard Cite

The mammalian thyroid gland is composed of 2 distinct endocrine cell populations concerned with the synthesis of 2 different classes of hormones. Follicular cells secrete the metabolically active iodothyronines whereas the C-(parafollicular) cells are concerned with the production ofcalcitonin, a hormone that influences blood levels of calcium and phosphorus, and bone cell metabolism. The synthesis of metabolic thyroid hormones is different than in other endocrine glands because the final assembly of hormone occurs within the follicular lumen. This extracellular synthesis of thyroid hormones is made possible by thyroglobulin, a glycoprotein synthesized by follicular cells. The secretion of thyroid hormones under the influence of pituitary thyrotrophin (TSH) from stores in the luminal colloid is initiated by elongation of microvilli and formation of pseudopods. FD&C Red No. 3 is a tetraiodinated derivative of fluorescein which in lifetime studies increases the incidence of thyroid follicular cell adenomas in male Sprague-Dawley rats. The striking changes in circulating levels of thyroid hormones and morphologic evidence of follicular cell stimulation are the result of alterations in the peripheral metabolism of thyroxine. An inhibition by FD&C Red No. 3 of 5'-deiodinase in the liver and kidney would explain the lower serum triiodothyronine (T,) levels. The pituitary, sensing the lowered circulating levels of T,, increased the secretion of thyroid stimulating hormone which resulted in the morphologic evidence of follicular cell stimulation in the long-term studies. Other xenobiotics increase the incidence of thyroid tumors in rodents by a direct effect on the thyroid gland to disrupt 1 of 3 or more possible steps in the biosynthesis of thyroid hormones. Physiologic perturbations alone, such as iodine deficiency or partial thyroidectomy, can disrupt thyroid hormone economy in rodents and, if sustained, increase the development of thyroid tumors. The wide variety of drugs, chemicals, and physiologic perturbations which increase thyroid tumor development appear to act through a secondary (indirect) mechanism to promote tumor development by causing a long-standing hypersecretion of thyroid stimulating hormone. Nodular and/or diffuse hyperplasia of C-cells occurs with advancing age in many strains of laboratory rats and in response to long-term hypercalcemia in certain animal species and human beings. Focal or diffuse hyperplasia often precedes the development of C-cell neoplasms. Radiation and the feeding of diets high in vitamin D resulting in hypercalcemia have been reported to increase the incidence of C-cell tumors in rats.

show abstract

Enhanced in vitro hepatic glucuronidation of thyroxine in rats following cutaneous application or ingestion of polychlorinated biphenyls

Cited by 45 publications

References 0 publications

Characterization of Potential Endocrine-Related Health Effects at Low-Dose Levels of Exposure to PCBs

Characterization of Potential Endocrine-Related Health Effects at Low-Dose Levels of Exposure to PCBs

The Significance of Hepatic Microsomal Enzyme Induction and Altered Thyroid Function in Rats: Implications for Thyroid Gland Neoplasia

The Effects of Xenobiotics on the Structure and Function of Thyroid Follicular and C-Cells

Contact Info

Product

Resources

About