Decrease In Serum T4 Concentration Research Articles

Hydroxylated Polybrominated Diphenyl Ethers and Bisphenol A in Pregnant Women and Their Matching Fetuses: Placental Transfer and Potential Risks

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are suspected endocrine disruptors, which can pass through the mammalian placenta and accumulate in the human maternal-fetal-placental unit. However, little is known about mechanisms of placental transfer and the associated risk(s). Ten OH-PBDE congeners, bisphenol A (BPA), total 17beta-estradiol (E2), and total thyroxine (T4) were quantified in blood serum from 26 pregnant women and 28 matching fetuses, including three pairs of twins from South Korea. Only 6-OH-BDE-47, a naturally occurring OH-PBDE, was detected at relatively great concentrations (maternal serum: 17.5 +/- 26.3 pg/g ww, fetal cord blood serum: 30.2 +/- 27.1 pg/g ww), which suggests that exposure was related to diets among Korean women. Concentrations of 6-OH-BDE-47 in maternal and cord serum were positively correlated, with concentrations being significantly greater in cord blood serum. The placental transfer ratio between fetal and maternal blood serum for 6-OH-BDE-47 (F/M ratio: 1.4 +/- 1.1) was different than the observed placental transfer ratio of BPA and previously reported values for hydroxylated polychlorinated biphenyls (OH-PCBs). This result is possibly due to large affinities to T4 transport proteins. Lesser concentrations of E2 and T4 were detected in cord blood serum (E2: 4.7 +/- 2.2 ng/mL, T4: 8.5 +/- 1.7 microg/dL) compared to maternal blood serum (E2: 8.0 +/- 3.0 ng/mL, T4: 9.7 +/- 1.8 microg/dL). A major effect of OH-PBDE exposure might be a decrease in serum T4 concentrations. Potential risks associated with disruption of T4 transport to the developing fetus such as negative consequences for fetal neurological development should be considered in further studies.

Role of the Constitutive Androstane Receptor in Xenobiotic-Induced Thyroid Hormone Metabolism

The induction of hepatic drug metabolizing enzymes alters not only the metabolism of the xenobiotic substances that induce them but also the metabolism of various endogenous hormones. The xenobiotic receptor constitutive androstane receptor (CAR) (NR1I3) mediates the well-studied induction of CYP2B genes and other drug-metabolizing enzymes by phenobarbital (PB), an antiepileptic drug that has been shown to alter thyroid hormone (TH) levels. Here we show that CAR is required for PB-mediated disruption of TH homeostasis and the induction of thyroid follicular cell proliferation. Treatment with PB or the more potent and more effective CAR ligand 1, 4-bis-[2-(3, 5,-dichloropyridyloxy)] benzene resulted in universal induction of thyroid hormone glucuronidation and sulfation pathways in a CAR-dependent manner. This resulted in a decrease in serum T4 concentration and a concomitant increase in serum TSH levels. CAR activation also decreased serum T3 levels in mice in which T3 production was blocked. The increase in serum TSH levels resulted in the stimulation of thyroid-follicular cell proliferation. These results highlight the central role of the xenosensor CAR in drug-hormone interactions.

Endotoxn-induced nonthyroidal illness in dogs.

To determine the effects of endotoxin administration on thyroid function test results and serum tumor necrosis factor-alpha (TNF-alpha) activity in healthy dogs. 6 healthy adult male dogs. Serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3'5'-triiodothyronine (rT3), free T4 (fT4), and endogenous canine thyroid stimulating hormone (TSH), and TNF-alpha activity were measured before (day-1; baseline), during (days 0 to 3), and after (days 4 to 24) IV administration of endotoxin every 12 hours for 84 hours. Compared with baseline values, serum T3 concentration decreased significantly, whereas rT3 concentration increased significantly 8 hours after initial endotoxin administration. Serum T4 concentration decreased significantly at 8 and 12 hours after initiating endotoxin administration. Serum T4 concentration returned to reference range limits, then decreased significantly on days 6 to 12 and 16 to 20. Serum fT4 concentration increased significantly at 12, 24, and 48 hours after cessation of endotoxin treatment, compared with baseline values. Serum rT3 concentration returned to reference range, then decreased significantly days 5 and 7 after stopping endotoxin treatment. Serum TNF-alpha activity was significantly increased only 4 hours after initial endotoxin treatment, compared with baseline activity. Endotoxin administration modeled alterations in thyroid function test results found in dogs with spontaneous nonthyroidal illness syndrome. A decrease in serum T4 andT3 concentrations and increase in serum rT3 concentration indicate impaired secretion and metabolism of thyroid hormones. The persistent decrease in serum T4 concentration indicates that caution should be used in interpreting serum T4 concentrations after resolution of an illness in dogs.

Effects of Amiodarone and Desethylamiodarone on Pituitary Deiodinase Activity and Thyrotropin Secretion in the Rat

The effect of acute administration of amiodarone, its major metabolite desethylamiodarone and iodine in an amount equal to that contained in amiodarone on serum thyroid hormone and thyrotropin (TSH) concentrations and hepatic and pituitary 5' deiodination of thyroxine (T4) in the euthyroid and hypothyroid rat was evaluated. Amiodarone, desethylamiodarone and iodine all caused a decrease in serum T4 and triiodothyronine (T3) concentrations in euthyroid rats, while serum TSH concentrations and pituitary and hepatic 5' deiodinase activities were decreased only in the amiodarone and desethylamiodarone-treated animals. Serum TSH was increased in the iodine treated rats. Amiodarone, but not iodine, decreased serum T3 and TSH concentrations and pituitary and hepatic 5' deiodinase activities in hypothyroid rats. Inhibition of hepatic 5' deiodinase activity was also observed by the addition of amiodarone in vitro in the absence of dithiothreitol (DTT) but not in the presence of DTT. The decrease in the serum T4 concentration observed with amiodarone and desethylamiodarone administration is probably secondary to the inhibitory effect of iodine released from the drugs on thyroidal T4 synthesis and secretion. Iodine inhibition of thyroidal T3 synthesis and secretion, decreased T4 substrate for a peripheral generation of T3 and inhibition of T4 to T3 conversion all contribute to the decrease in serum T3 observed. The decrease in the serum TSH concentration, despite low serum T4 and T3 concentrations and inhibition of pituitary 5' deiodinase, suggest that amiodarone may function as a thyroid hormone agonist in the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)