Thyroxine and 3,3′,5-Triiodothyronine Are Glucuronidated in Rat Liver by Different Uridine Diphosphate-Glucuronyltransferases*

Beetstra, J. B.; Engelen, J.G.M. van; Karels, P.; Hoek, H. J. Van Der; Jong, Marion de; Docter, R.; Krenning, E. P.; Hennemann, G; Brouwer, Abraham; Visser, Theo J.

doi:10.1210/endo-128-2-741

Cited by 119 publications

(82 citation statements)

References 22 publications

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“…McCleary (2001) began development of this assay by modifying/combining the methods of Beetstra et al (1991), and Barter and Klaassen (1992a), which describe an assay previously validated for use on rodents. I further modified McCleary's methods for use in quail.…”

Section: Development Of An Assay For Measuring Avian Udp-gt Activity mentioning

confidence: 99%

Polychlorinated biphenyl effects on avian hepatic enzyme induction and thyroid function

Webb

McNabb

2008

General and Comparative Endocrinology

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Section: Development Of An Assay For Measuring Avian Udp-gt Activity mentioning

confidence: 99%

Polychlorinated biphenyl effects on avian hepatic enzyme induction and thyroid function

Webb

McNabb

2008

General and Comparative Endocrinology

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“…Cheek et al (35) found that it was only the hydroxylated PCBs, not the parent compounds, that bound to transthyretin and thyroid-binding globulin and report that they had the same affinity for transthyretin as thyroid hormone. They may also activate uridine diphosphate-glucuronyltransferase, which then increases the biliary excretion of T 4 -glucuronide (31,36). In a recent review, Brucker-Davis (37) concluded that except in the fetus the major mode of action of coplanar congeners is through increased glucuronidation, whereas the ortho-substituted congeners, and particularly their oxidative metabolites, act through multiple other pathways, including interference with transport proteins, direct action on the thyroid gland, and changes in the kinetics of thyroid hormone metabolism.…”

Section: Thyroid Diseasementioning

confidence: 99%

Incidence of endocrine disease among residents of New York areas of concern.

Carpenter

Shen

Nguyen

et al. 2001

Environ Health Perspect

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There are six Areas of Concern, as identified by the International Joint Commission, located in New York State. Three are contiguous in western New York and have similar contaminants (Buffalo River, Niagara River, and 18 Mile Creek). We used the Statewide Planning and Research Cooperative System database, which records diagnoses according to the (italic)International Classification of Disease, Ninth Revision(/italic) codes for all patients admitted to state-regulated hospital facilities, to compare incidence of selected diseases reported in hospitalized patients who reside in ZIP codes that are within 15 miles of any of these sites to those of residents of three different control populations: all residents of the rest of New York State (including New York City), all residents of ZIP codes outside New York City that do not contain any site identified as a federal or state Superfund site, and all residents of ZIP codes outside New York City that contain a federal or state Superfund site that does not have one or more persistent organic pollutants listed as a major contaminant. We found a significant elevation of disorders of the thyroid gland in women, but not in men, of all ages greater than 25 years on all three comparisons, as well as an increased incidence of morbidity from diseases of the female genital tract in women between age 25 to greater than 75 years for all comparison groups. There was also a significant elevation in incidence of endometriosis in women 25-44 years of age. All these elevations were significant at the 99% confidence level. Incidence of diseases of ovaries and testes and female infertility were not different from those in the rest of New York State. Although many factors influence incidence of thyroid and genital diseases, our results are consistent with the hypothesis that exposure to environmental contaminants through residence near polluted sites may be a factor.

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“…Analysis of thyroxin UDP-glucuronosyltransferase (T 4 UDPGT): T 4 UDPGT activities in hepatic microsomes were determined according to the method of Beetstra et al [2]. The microsome sample (1 mg protein/ml) was incubated with 1 µM T 4 (Sigma, St. Louis, MO, U.S.A.) and 0.1 µCi 125 I-T 4 (New England Nuclear, Boston, MA, U.S.A.) in 0.1 M Tris-HCl buffer (pH 7.4) containing 5 mM MgCl 2 and 0.05% Brij 56 (Sigma, St. Louis, MO, U.S.A.).…”

Section: Animals and Treatmentmentioning

confidence: 99%

Thyroid Hyperactivity Induced by Methimazole, Spironolactone and Phenobarbital in Marmosets (Callithrix jacchus): Histopathology, Plasma Thyroid Hormone Levels and Hepatic T4 Metabolism.

Kurata

Wako

Tanaka³

et al. 2000

The Journal of Veterinary Medical Science

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ABSTRACT. To determine drug-induced hyperfunction of marmoset thyroids due to inhibition of synthesis or enhancement of metabolic elimination of thyroid hormones, males were orally administered 10 and 30 mg/kg/day methimazole (MMI), 30 and 100 mg/kg/day spironolactone (SPL), or 50 mg/kg/day phenobarbital (PB) for 4 weeks. MMI caused marked hypertrophy of follicular epithelial cells in accordance with a significant decrease in the plasma thyroxin (T 4 ) level. Hypertrophied epithelial cells were filled with dilated rough endoplasmic reticulum and reabsorbed intracellular colloids, and the luminal surface was covered with abundant microvilli. The colloid included vacuoles positive to anti T 4 immuno-staining. SPL and PB also caused similar histomorphological changes, although they were less severe than those due to MMI and were not clearly associated with decrease in the plasma T 4 levels. Hepatic T 4 UDPGT activities tended to increase due to SPL and PB treatment, however, which were not so significant as increases in microsomal cytochrome P-450 contents. Some animals treated with SPL and PB showed marked increases in thyroid weights due to inactive dilated follicles. In conclusion, hyperactivity of thyroid follicles was induced in marmosets not only due to inhibition of T 4 synthesis produced by MMI but also because of enhancement of hepatic T 4 elimination produced by SPL and PB. However, hypertrophic effects of SPL and PB were less severe than MMI, because plasma T 4 levels were maintained at almost pretreatment or control levels after SPL or PB treatment.-KEY WORDS: marmoset, methimazole, phenobarbital, spironolactone, thyroid hyperactivity.Many chemicals cause thyroid proliferative lesions through non-genotoxic mechanisms in the rat. These chemicals disturb the hypothalamus-pituitary-thyroid gland axis by inhibiting thyroid hormone synthesis (i.e. antithyroid drugs) or by enhancing hormone metabolism (i.e. hepatic microsomal enzyme inducers) and cause thyroid proliferative lesions secondary to hormone imbalance. Under normal conditions, circulating levels of thyroid hormones are maintained at constant levels via the feedback mechanism among the hypothalamus, pituitary and thyroid glands. Continuous reduction in circulating levels of thyroid hormones due to chemical-treatment also results in a compensatory increase of thyroid stimulating hormone (TSH) through the feedback mechanism. Overstimulation of the thyroid gland by TSH induces follicular cell hypertrophy, hyperplasia and finally neoplasia [3,6,8,10,21].However, there are marked species differences in thyroid gland physiology. The most obvious species difference between the rat and humans is the lack of thyroxin binding globulin (TBG) in the rat [13,24]. TBG has the highest affinity for thyroxin [4]. Lack of this protein leads to more T 4 free of protein binding and makes it easier to remove from the body in rats than in humans. Therefore, the halflife of serum T 4 is 12 to 24 hrs in the rat versus 6 to 7 days in humans and serum TSH is 20-fold higher i...

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Thyroxine and 3,3′,5-Triiodothyronine Are Glucuronidated in Rat Liver by Different Uridine Diphosphate-Glucuronyltransferases*

Cited by 119 publications

References 22 publications

Polychlorinated biphenyl effects on avian hepatic enzyme induction and thyroid function

Polychlorinated biphenyl effects on avian hepatic enzyme induction and thyroid function

Incidence of endocrine disease among residents of New York areas of concern.

Thyroid Hyperactivity Induced by Methimazole, Spironolactone and Phenobarbital in Marmosets (Callithrix jacchus): Histopathology, Plasma Thyroid Hormone Levels and Hepatic T4 Metabolism.

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