Decrease In Serum Thyroxine Level Research Articles

Comparative study on 2,2′,4,5,5′-pentachlorobiphenyl-mediated decrease in serum thyroxine level between C57BL/6 and its transthyretin-deficient mice

The relationships between the changes in the levels of serum total thyroxine (T4), serum T4-transthyretin (TTR) complex, and accumulation of T4 in tissues by 2,2′,4,5,5′-pentachlorobiphenyl (PentaCB) were examined using wild-type C57BL/6 (WT) and its TTR-deficient (TTR-null) mice. The constitutive level of serum total T4 was much higher in WT mice than in TTR-null mice. In WT mice 4days after a single intraperitoneal injection with PentaCB (112mg/kg), serum total T4 level was significantly decreased along with a decrease in serum T4–TTR complex, and the levels of serum total T4 in the PentaCB-treated WT mice were almost the same to those in PentaCB-untreated (control) TTR-null mice. In addition, a slight decrease in serum total T4 by PentaCB treatment was observed in TTR-null mice. Furthermore, clearance of [125I]T4 from the serum after [125I]T4-administration was promoted by the PentaCB-pretreatment in either strain of mice, especially WT mice. On the other hand, accumulation level of [125I]T4 in the liver, but not in extrahepatic tissues, was strikingly enhanced in the PentaCB-pretreated WT and TTR-null mice. Furthermore, in both strains of mice, PentaCB-pretreatment led to significant increases in the steady-state distribution volume of [125I]T4 and the concentration ratio of the liver to serum. The present findings demonstrate that PentaCB-mediated decrease in serum T4 level occurs mainly through increase in accumulation level of T4 in the liver and further indicate that the increased accumulation of T4 in the liver of WT mice is primarily dependent on the PentaCB-mediated inhibition of serum T4–TTR complex formation.

A possible mechanism for the decrease in serum thyroxine level by phenobarbital in rodents

Effects of phenobarbital (PB) on the levels of serum thyroid hormones such as total thyroxine (T 4) and triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs. One day after the final administration of PB (80 mg/kg, intraperitoneal, once daily for 4 days), significant decreases in the levels of the serum total T 4 and free T 4 occurred in mice, hamsters, and rats, while a significant decrease in the level of serum triiodothyronine was observed in hamsters and rats among the animals examined. In addition, a significant decrease in the level of serum thyroid-stimulating hormone was observed in only hamsters among the rodents examined. Significant increases in the level and activity of hepatic T 4-UDP-glucuronosyltransferase (UGT1A) after the PB administration occurred in mice, hamsters, and rats, while the increase in the amount of biliary [ 125I]T 4-glucuronide after an intravenous injection of [ 125I]T 4 to the PB-pretreated animals occurred only in rats. In mice, rats, and hamsters, but not guinea pigs, PB pretreatment promoted the clearance of [ 125I]T 4 from the serum, led to a significant increase in the steady-state distribution volumes of [ 125I]T 4, and raised the concentration ratio (Kp value) of the liver to serum and the liver distribution of [ 125I]T 4. The present findings indicate that the PB-mediated decreases in the serum T 4 level in mice, hamsters, and rats, but not guinea pigs, occur mainly through an increase in the accumulation level of T 4 in the liver.

Polychlorinated Biphenyl-Mediated Decrease in Serum Thyroxine Level in Rodents

Effects of Kanechlor-500 (KC500), a commercial polychlorinated biphenyl mixture, on the levels of serum thyroid hormones such as total thyroxine (T(4)) and triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs. Four days after a single intraperitoneal injection of KC500, significant decreases in the levels of the serum total T(4) and free T(4) occurred in all the animals examined, whereas a significant decrease in the level of serum triiodothyronine was observed only in guinea pigs among the animals examined. In addition, no significant change in the level of serum thyroid-stimulating hormone was observed in any of the rodents examined. A significant increase in the activity of hepatic T(4)-UDP-glucuronosyltransferase after the KC500 administration occurred only in guinea pigs, whereas the increase in the amount of biliary [(125)I]T(4) glucuronide after an intravenous injection of [(125)I]T(4) to the KC500-pretreated animals occurred only in rats. On the other hand, in all the rodents examined, KC500-pretreatment promoted the clearance of [(125)I]T(4) from the serum and led to a significant increase in the steady-state distribution volumes of [(125)I]T(4). Likewise, its pretreatment raised the concentration ratio (K(p) value) of the liver to serum and the liver distribution of [(125)I]T(4) in all the rodents tested. The present findings indicate that for the first time the KC500-mediated decrease in the serum T(4) level in mice, hamsters, rats and guinea pigs occurs mainly through an increase in the accumulation level of T(4) in the liver.

Biologic markers in blood reflecting thyroid hormone effect at peripheral tissue level in patients receiving levothyroxine replacement for hypothyroidism.

Plasma fibronectin, serum procollagen-III-peptide and sex-hormone binding globulin as not specific markers of thyroid hormone effect at peripheral tissue level were determined and their values were related with serum levels of TSH, free-thyroxine and triiodothyronine during levothyroxine sodium replacement therapy for hypothyroidism. Low levels of biologic markers characteristic of hypothyroidism were normalized in consequence of hormone replacement and a negative correlation between their serum levels and TSH concentration was demonstrated in most subjects. However, in some patients a discrepancy in the response to levothyroxine between the pituitary and other target organs could be revealed. Additional evidence was disclosed that the pituitary thyrotroph sensitizes a minor decrease in serum thyroxine level, which would not be recognized by other target organs. Furthermore, it was revealed that during L-T4 replacement therapy in a large fraction of patients with subnormal serum TSH concentration blood levels of the measured markers often exceeded the upper limit of the normal range indicating the possibility of "tissue"-thyrotoxicosis beside the pituitary in other target organs, too. According to the present study which takes into consideration markers reflecting end-organ responsiveness to thyroid hormones it is recommended to adjust the dose of levothyroxine to maintain serum TSH in the normal range. For patients with subnormal TSH concentration a close follow-up is obligatory and in case od concomitantly raised free-thyroxine level the reduction of the levothyroxine dosage is proposed.

4-Hydroxy-2,2′,3,4′,5,5′,6-heptachlorobiphenyl-Mediated Decrease in Serum Thyroxine Level in Mice Occurs through Increase in Accumulation of Thyroxine in the Liver

4-Hydroxy-2,2',3,4',5,5',6-heptachlorobiphenyl (4-OH-CB187) was selected as a major hydroxylated polychlorinated biphenyl metabolite detected from serum of wildlife and humans and was examined for its effect on level of serum thyroid hormone in mice. Four days after treatment of C57BL/6 and DBA/2 mice with 4-OH-CB187 (1.0 mg/kg), the serum total thyroxine (T(4)) and free T(4) levels were decreased in both strains of mice. On the other hand, no significant changes in the level and activity of the T(4)-UDP-glucuronosyltransferases, including UGT1a and UGT1a1, by the 4-OH-CB187 treatment were observed in either strain of mice. No 4-OH-CB187-mediated change in level of serum thyroid-stimulating hormone was observed in either strain of mice. Binding levels of [(125)I]T(4) to serum proteins after administration of [(125)I]T(4) were significantly changed in 4-OH-CB187-pretreated mice: a decrease in the level of serum [(125)I]T(4)-transthyretin (TTR) complex and an increase in the binding level of [(125)I]T(4) to serum albumin and thyroxine binding protein in both strains of mice. Clearance from serum of T(4) was promoted by 4-OH-CB187 pretreatment in both C57BL/6 and DBA/2 mice, and the levels of T(4) in several tissues, especially the liver, were increased. In addition, 4-OH-CB187-mediated decreases in serum total T(4) and free T(4) levels were observed in wild-type and TTR-heterozygous mice but not in TTR-deficient mice. The present findings show that 4-OH-CB187 shows a definite ability to decrease serum T(4) level and further indicate that the 4-OH-CB187-induced decrease would occur through increase in accumulation of T(4) in the liver.

4-OH-2,2',3,4',5,5',6-heptachlorobiphenylによる血中甲状腺ホルモン濃度の低下作用機構の解明

4-OH-2,2',3,4',5,5',6-heptachlorobiphenylによる血中甲状腺ホルモン濃度の低下作用機構の解明

A Novel Mechanism for Polychlorinated Biphenyl-Induced Decrease in Serum Thyroxine Level in Rats

We have previously suggested that the decrease in the levels of serum total thyroxine (T(4)) and free T(4) by a single administration to rats of Kanechlor-500 (KC500) at a dose of 100 mg/kg is not necessarily dependent on the increase in hepatic T(4)-UDP-glucuronosyltransferase (UDP-GT). In the present study, we determined whether or not a consecutive treatment with KC500 at a relatively low dose (10 mg/kg i.p., once daily for 10 days) results in a decrease in the level of serum total T(4) and further investigated an exact mechanism for the KC500-induced decrease in the T(4). At 4 days after final treatment with KC500, the serum total T(4) and free T(4) levels were markedly decreased in both Wistar and UGT1A-deficient Wistar (Gunn) rats, whereas significant increases in hepatic T(4)-UDP-GT activity were observed in Wistar rats but not in Gunn rats. The level of serum thyroid-stimulating hormone was not significantly changed in either Wistar or Gunn rats. Clearance from serum of the [(125)I]T(4) administered to the KC500-pretreated Wistar and Gunn rats was faster than that to the corresponding control (KC500-untreated) rats. The accumulated level of [(125)I]T(4) was increased in several tissues, especially the liver, in the KC500-pretreated rats. The present findings demonstrated that a consecutive treatment with KC500 resulted in a significant decrease in the level of serum total T(4) in both Wistar and Gunn rats and further indicated that the KC500-induced decrease would occur through increase in accumulation of T(4) in several tissues, especially the liver, rather than increase in hepatic T(4)-UDP-GT activity.

Delay in natural decline of lactase activity in the small intestine of prematurely weaned rats as related to changes in their thyroid status.

Premature weaning of suckling rats on the 15th day of life delayed the natural reduction of lactase activity in the small intestine and reduced the level of T4 in serum. Preliminary treatments (from day 12 to 14 of life) with exogenous T4 (1 mg/kg BW) or exposure to cold (10 degrees C) significantly increased the level of T4 in serum on the 15th day of life, and sharply accelerated the reduction of lactase activity. It is concluded that the delay in lactase reduction in prematurely weaned rats may be related to a decrease in serum thyroxine level. Cold as well as exogenous thyroxine may be considered as a means for regulation of the functional maturation of the small intestine.

Functional alterations in the hypothalamic-pituitary-thyroid axis in rats exposed prenatally to diazepam

Prenatal exposure to diazepam in the rat from day 15 to day 21 of gestation induced a decrease in serum thyroxine levels in both male and female animals at 3 and 6 weeks of age. Furthermore, female rats exposed prenatally to diazepam showed an increase in the TSH response to synthetic thyrotropinreleasing hormone (TRH) when tested at 10–12 weeks of age, though their serum thyroxine level was normal. The results suggest that prenatal exposure to diazepam in rats during the last week of gestation affects the functional development of hypothalamic-pituitary-thyroid axis.

Effects of hypothyroidism on development of nitrosomethylurea-induced tumors of the mammary gland, thyroid gland, and other tissues.

AbstractFemale rats were injected with the mammary gland carcinogen N-nitrosomethylurea (NMU) and were made hypothyroid by treatment with either propylthiouracil (PTU) or 131I. NMU (25–100 mg/kg) itself caused a dose-related increase in serum thyroxine levels. PTU (1.0–3.0 mg/100 ml of drinking water) caused a decrease in serum thyroxine and triiodothyronine levels in NMU-treated rats. At 28–31 weeks after injection of NMU alone, 9/43 rats (21%) had malignant mammary tumors. This incidence was increased to 11/30 (37% P > 0.1) and 13/30 (43% P P > 0.05) and caused a 33% decrease in final body weight. Treatment with 10 μCi of 131I gave a small decrease in serum thyroxine levels in NMU-treated rats and increased the incidence of malignant mammary tumors to 11/26 rats (42%, 0.1 > P > 0.05). In addition, PTU (0.3 mg/100 ml) plus NMU induced ...