Thyroid Status Of Rats Research Articles

Regulatory Effects of 5-Day Oral and Intraperitoneal Administration of a Thienopyrimidine Derivative on the Thyroid Status in Rats.

In experiments on rats, we studied the effect of 5-day intraperitoneal (15 mg/kg/day) and oral (40 mg/kg/day) administration of compound TPY3m, a stimulator of the production of thyroid hormones by the thyroid gland developed by us, on the blood levels of thyroxine, triiodothyronine, and thyroid-stimulating hormone and on morphology of the thyroid gland. With both routes of administration, TPY3m caused a sustained moderate elevation of thyroid hormones, mainly thyroxine, with little effect on the level of thyroid-stimulating hormone. TPY3m did not reduce the stimulating effect of thyroliberin on the levels of thyroid hormones and had no damaging effect on the thyroid gland. During long-term administration, compound TPY3m stimulates the production of thyroid hormones without weakening the activity of the thyroid axis. Thus, TPY3m is a prototype of drugs for correcting thyroid hormone deficiency.

Effects of High Doses of Sodium Metavanadate on the Thyroid Status in Rats

Introduction: The widespread use of vanadium in the metallurgical industry leads to its high content in the workplace air, which poses a threat to human health both in the workforce and the community. Vanadium accumulates in many organs and has a toxic effect; yet, studies of its effects on the thyroid gland are scarce and narrowly focused. This study is aimed at establishing the effect of vanadium on the functioning of the thyroid gland. Objective: To establish thyroid status in rats after a single intraperitoneal injection of sodium metavanadate. Materials and methods: Twenty-six male Wistar rats aged 3 months weighing more than 200 g were divided into a control group (10 animals) exposed to distilled water and two exposure groups (V11 and V18) of eight animals each intraperitoneally exposed to 11 and 18 mg of sodium metavanadate per kg of body weight, respectively. Serum levels of the thyroid-stimulating hormone, total and free thyroxine and triiodothyronine were determined by enzyme immunoassay. Results: We observed that the high single exposure dose of sodium metavanadate caused significant changes in thyroid hormone levels. Administration of sodium metavanadate at the dose of 11 mg/kg b.w. induced an increase in the levels of total and free thyroxine but a decrease in the ratio of total triiodothyronine to total thyroxine compared with the controls. Administration of a higher dose of the compound (18 mg/kg b.w.) increased the levels of free triiodothyronine, free thyroxine, the ratio of free triiodothyronine to total triiodothyronine, and the ratio of free thyroxine to total thyroxine compared with the controls. We also noted the differences in health effects between the exposure groups, such as a higher level of free triiodothyronine and higher ratios of free triiodothyronine to total triiodothyronine and of free thyroxine to total thyroxine in the V11 exposure group. Conclusions: Our findings show that a single intraperitoneal injection of sodium metavanadate at high doses of 11 and 18 mg/kg b.w. suppresses thyroid function and induces hypothyroidism, even 14 days after administration.

On the significance of the activity of liver arginase and Kupffer cells in the development of secondary atherogenic dyslipidemia and the formation of thyroid status in rats with experimental peritonitis

Peritonitis is one of the most severe complications of various diseases and injuries of the abdominal organs. The diagnosis of peritonitis in a general sense implies any form and severity of inflammation of the peritoneum. Currently, the problem of peritonitis remains actual, despite the achievements of scientific and technological progress. So, despite the successes of modern surgery, the achievements of asepsis and antiseptics, the rather wide possibilities of antibacterial, infusion and detoxification therapy, the incidence of peritonitis and mortality from it remain at a high level. The aim of the study was to elucidate the significance of the activity of liver arginase and Kupffer cells in the development of secondary atherogenic dyslipidemia and the formation of thyroid status in rats with experimental peritonitis. It has been established that under conditions of experimental peritonitis in rats, the activity of liver arginase decreases, the content of NO3 – /NO2 – increases and the level of iodine-containing thyroid hormones in the blood decreases, secondary atherogenic dyslipoproteinemia develops. Liver arginase and Kupffer cells are involved in changes in the content of total cholesterol in the liver, total cholesterol, lipoprotein cholesterol, the level of iodine-containing hormones in the blood and body temperature in peritonitis. A decrease in the activity of Kupffer cells in peritonitis is accompanied by an increase in the level of triiodothyronine in the blood, a less pronounced decrease in the activity of liver arginase and a weakening of the development of characteristic changes in the content of total cholesterol in the liver, lipoprotein cholesterol in the blood and prevents the development of secondary dyslipoproteinemia. Depression of liver arginase in conditions of peritonitis aggravates changes in the content of total cholesterol in blood and liver lipoproteins, triiodothyronine in the blood and contributes to the development of secondary dyslipoproteinemia.

Роль тиреоїдних гормонів у формуванні просторової пам’яті щурів у ранньому онтогенезі

Changes in behavioral and mnestic activity, as well as their neurochemical support in thyroid dysfunction were determined in juvenile Wistar rats. Behavioral activity was studied in an elevated cruciform labyrinth, the study of spatial memory was performed by the development of protective avoidance reaction in the Morris water labyrinth, and by the production of food reactions in the 8-beam labyrinth. The content of free amino acids of the neurotransmitter spectrum and serotonin was determined by thin layer chromatography followed by spectrophotometry. It was found that thyroid dysfunction in early ontogenesis was accompanied by significant impairments of emotional and cognitive activity depending on the thyroid status of rats; differences in the mechanisms of the formation of spatial memory with negative and positive reinforcement were also found. At the same time, the anxiolytic type of behavior and formation of spatial memory in juvenile animals with experimental hyperthyroidism are possibly provided by an increase in GABA content in the neocortex by 40% and a decrease in serotonin level in the hippocampus by 32%. Experimental hypothyroidism caused an anxiogenic effect and cognitive impairment, which were accompanied by an excessive increase by 51% in the neocortical serotonin content.

Interaction of liver arginase and L-arginine-NO system in the processes of detoxification, lipid peroxidation and the formation of the thyroid status in rats with chronic ethanol intoxication

A sufficient number of facts testifying the importance of liver arginase and nitrogen monoxide in the life processes in the normal and pathological conditions have been accumulated to date. The aim of the study was to determine the significance of the relationship and interaction of liver arginase and L-arginine-NO system in the processes of detoxification, lipid peroxidation and the formation of the thyroid status in rats with chronic ethanol intoxication. In rat experiments using the modern physiological, biochemical research methods and a pharmacological approach, it was found that chronic ethanol intoxication leads to a decrease in the liver arginase activity and the triiodothyronine concentration. At the same time, the increase in the level of “average molecules”, NO3 – /NO2 –, the content of lipid peroxidation products in the plasma, as well as the increase in the blood toxicity degree, the activity of alanine amino transferase, aspartate amino transferase and the narcotic sleep duration were observed. Hyperthyroid rats demonstrated the increased liver arginase activity, the processes of detoxification, lipid peroxidation and body temperature while rats with the experimental hypothyroidism showed the opposite results. The liver arginase depression caused by the injection of Nω-hydroxy-nor-L-arginine (Nor-NOHA), or L-valine into the body prevents the body temperature increase and the development of characteristic changes in the detoxification and lipid peroxidation processes acted upon by exogenous triiodothyronine. Under the conditions of the liver arginase inhibition by Nor-NOHA or L-valine, the ethanol action is accompanied by a more significant inhibition of the liver detoxification function and an increase of NO3 – /NO2 – levels in blood plasma. The preliminary injection of an NG-nitro-L-arginine methyl ester inhibitor of NO-synthase into the animal’s body weakensthe toxic ethanol effect on the liver, as well asthe development of characteristic changes in the liver arginase activity, in the processes of detoxification and lipid peroxidation in rats with chronic ethanol intoxication. Apparently, the activity of liver arginase and L-arginine-NO system determines the severity of detoxification, lipid peroxidation processes and the formation of the thyroid status in the conditions of chronic alcoholization, which is important in the ethanol intoxication pathogenesis.

The thyroid status of rats immunized with peptides derived from the extracellular regions of the types 3 and 4 melanocortin receptors and the 1B-subtype 5-hydroxytryptamine receptor

The activity of the hypothalamic-pituitary-thyroid (HPT) axis is controlled by the brain neurotransmitter systems, including the melanocortin signaling system. Pharmacological inhibition of type 4 melanocortin receptor (M4R) leads to disruption of the functioning of HPT axis and to reduction of the level of thyroid hormones. At the same time, the data on how prolonged inhibition of M4R affects this axis and on its role in regulation of M3R are absent. The relationship between the thyroid status and the activity of 1B-subtype 5-hydroxytryptamine receptor (5-HT1BR) is scarcely explored. The aim of this work to study the effects of chronic inhibition of M3R, M4R and 5-HT1BR induced by immunization of rats with BSA-conjugated peptide derived from the extracellular regions of these receptors on the thyroid status and the activity of thyroid stimulating hormone (TSH)-sensitive adenylyl cyclase signaling system (ACSS) in the thyroid glarid (TG) of the immunized animals. In rats immunized with the peptides K-[TSLHL WNRSSHGLHG11-25]-A of M4R, A[PTNPYCICTTAH269-280]-A of M3R and. [QAKAEE-EVSEC(Acm)-VVNTDH189-205]-A of 5-HT1BR levels of thyroid hormones such as fT4, tT4 and tT3 were significantly reduced. In rats immunized with M4R and M3R peptides, an increase of TSH was detected whereas in the animals immunized with 5-HT1BR peptide the level of TSH, on the contrary, was reduced. In the TG of rats immunized with M4R and M3R peptides, the stimulatory effects of hormones (TSH, PA-CAP-3 8) and GppNHp on adenylyl cyclase activity were attenuated, and the changes were most pronounced in the case M4R peptide immunization. After immunization with 5-HT1BR peptide the stimulatory effects of TSH, PACAP-38 and GppNHp were retained. Thus, the main cause of thyroid hormones deficit in rats immunized with M4R and M3R peptides was the decreased sensitivity of ACSS thyrocytes to TSH, whereas in rats iimunized with 5-HT1BR peptide the deficit of thyroid hormones was associated with decreased level of TSH. Our data on the negative impact of long-term immunization of rats with BSA-conjugated peptides derived from the extracellular regions of M4R, M3R.and 5-HT1BR on their thyroid status is a strong argument in favor of participation of these receptors and intracellular signaling pathways associated with them in the regulation of HPT axis.

Proportions of Myosin Heavy Chain mRNAs, Protein Isoforms and Fiber Types in the Slow and Fast Skeletal Muscles Are Maintained After Alterations of Thyroid Status in Rats

Recently, we have established that slow soleus (SOL) and fast extensor digitorum longus (EDL) muscles of euthyroid (EU) Lewis rats posses the same proportions between their four myosin heavy chain (MyHC) mRNAs, protein isoforms and fiber types as determined by real time RT-PCR, SDS-PAGE and 2-D stereological fiber type analysis, respectively. In the present paper we investigated if these proportions are maintained in adult Lewis rats with hyperthyroid (HT) and hypothyroid (HY) status. Although HT and HY states change MyHC isoform expression, results from all three methods showed that proportion between MyHC mRNA-1, 2a, -2x/d, -2b, protein isoforms MyHC-1, -2a, -2x/d, -2b and to lesser extent also fiber types 1, 2A, 2X/D, 2B were preserved in both SOL and EDL muscles. Furthermore, in the SOL muscle mRNA expression of slow MyHC-1 remained up to three orders higher compared to fast MyHC transcripts, which explains the predominance of MyHC-1 isoform and fiber type 1 even in HT rats. Although HT status led in the SOL to increased expression of MyHC-2a mRNA, MyHC-2a isoform and 2A fibers, it preserved extremely low expression of MyHC-2x and -2b mRNA and protein isoforms, which explains the absence of pure 2X/D and 2B fibers. HY status, on the other hand, almost completely abolished expression of all three fast MyHC mRNAs, MyHC protein isoforms and fast fiber types in the SOL muscle. Our data present evidence that a correlation between mRNA, protein content and fiber type composition found in EU status is also preserved in HT and HY rats.

Changes in thyroid status of rats after prolonged exposure to low dose dichlorodiphenyltrichloroethane.

The effect of low dose dichlorodiphenyltrichloroethane (DDT), omnipresent ecotoxicant and endocrine disruptor, on the functioning of the endocrine system is an urgent problem. We studied the effect of low dose DDT on thyroid status in rats. Rats receiving DDT in a dose of 1.890±0.086 μg/kg for 6 weeks showed increased concentrations of thyroid hormones, particularly triiodothyronine, and reduced level of thyrotropin. Longer exposure reduced the production of thyroid hormones. The dynamics of thyroid status parameters during DDT treatment in a low dose was similar to changes observed during the development of hypothyroidism induced by iodine deficiency.

Serum Thyroid Hormone Levels in Epileptic Children Receiving Anticonvulsive Drugs

How to Cite this Article: Mahyar A, Ayazi P, Dalirani R, Hosseini SM, Daneshi Kohan MM. Serum Thyroid Hormone Levels in Epileptic Children Receiving AnticonvulsiveDrugs. Iranian Journal of Child Neurology 2011;5(4):21-24.ObjectiveThe aim of this study was to investigate serum thyroid hormone levels in epileptic children receiving anticonvulsive drugs.Materials & MethodsIn this case- control study, 30 epileptic children who were receiving anticonvulsive drugs (case group) were compared with 30 healthy children (control group). This study was carried out in the Qazvin Children's Hospital (Qazvin, Iran) from October to December 2007. Both groups were matched for age and sex. Thyroid hormone levels were measured using a radioimmunoassay and immunoradiometric assay. Data were analyzed using Chi-square and Student's t-tests.ResultsThe mean serum T3 and T4 levels in the case group were 2.36 ± 0.73 nmol/L and 95.96 ± 27.01 nmol/L, respectively, and the corresponding values in the control group were 1.88 ± 0.93 nmol/L and 147.46 ± 35.77 nmol/L, respectively. The mean serum thyroid-stimulating hormone (TSH) levels in the case and control groups were 2.73±0.73 mIU/mL and 2.49 ± 2.17mIU/mL, respectively.ConclusionThis study revealed that long-term consumption of anticonvulsive drugs resulted in a decline in serum T4 levels and an increase in serum T3 levels, but had no effect on TSH levels. 1. Johnston M. Neurodegenerative disorders of childhood;Spingolipidoses. Nelson textbook of pediatrics, 17th edPhiladelphia: Saunders; 2004.P.2031-2.2. Sankar R, Koh S, Wu J, Menkes J. Paroxysmal disorders.In(eds): Menkes JH, Sarnat HB, Maria BL. ChildNeurology; 2006.P.7:877.3. Shiva S, Ashrafi M, Mostafavi F, Abasi F, RahbariA, Shabanian R. Effects of anticonvulsant drugs onthyroid function tests. Iranian Journal of pediatrics2003;13(02):101.4. Kimura M, Yoshino K, Suzuki N, Maeoka Y. Effect ofantiepileptic drugs on thyroid function. Psychiatry andclinical neurosciences. 1995;49(4):227-9.5. Eris Pural J, Delrio-Garma M, Delrio - Castro – GagoM. Long Term treatment of children with epilepsy withvalprovats or carbamazepin, may cause subclinicalhypothyroidism. Epilepsia 1999;40(12):1961.6. Isojarvi JIT, Turkka J, Pakarinen AJ, Kotila M,Rattya J, Myllyla VV. Thyroid function in men takingcarbamazepine, oxcarbazepine, or valproate for epilepsy.Epilepsia 2001;42(7):930-4.7. Vainionpaa LK, Mikkonen K, Rattya J, Knip M,Pakarinen AJ, Myllyla VV, et al. Thyroid function ingirls with epilepsy with carbamazepine, oxcarbazepine,or valproate monotherapy and after withdrawal ofmedication. Epilepsia 2004;45(3):197-203.8. Verrotti A, Basciani F, Morresi S, Morgese G, ChiarelliF. Thyroid hormones in epileptic children receivingcarbamazepine and valproic acid. Pediatric neurology2001;25(1):43-6.9. Kantrowitz L, Peterson M, Trepanier L, Melian C,Nichols R. Serum total thyroxine, total triiodothyronine,free thyroxine, and thyrotropin concentrations in epilepticdogs treated with anticonvulsants. Journal of the AmericanVeterinary Medical Association 1999;214(12):1804.10. Schroder-van der Elst J, Van der Heide D, Van der BentC, Kaptein E, Visser T, DiStefano J. Effects of 5, 5 -diphenylhydantoin on the thyroid status in rats. Europeanjournal of endocrinology 1996;134(2):221.11. Schonberger W, Grimm W, Schonberger G, SinterhaufK, Scheidt E, Ziegler R. [The influence of primidone onthyroid function (author’s transl)]. Dtsch Med Wochenschr1979;104(25):915-7.12. Tiihonen M, Liewendahl K, Waltimo O, Ojala M,Valimaki M. Thyroid status of patients receiving longtermanticonvulsant therapy assessed by peripheralparameters: a placebo-controlled thyroxine therapy trial.Epilepsia 1995;36(11):1118-25.13. Benedetti MS, Whomsley R, Baltes E, Tonner F. Alterationof thyroid hormone homeostasis by antiepileptic drugsin humans: involvement of glucuronosyltransferaseinduction. Eur J Clin Pharmacol 2005;61(12):863-72.

Morphofunctional Analysis of Development of Nonthyroid Disease Syndrome in Experimental Endotoxicosis

The development of the nonthyroid disease syndrome in acute endotoxicosis involves mechanisms related to polarization of the immune response by the Th1 type. Thyroid status of rats with pronounced and weak polarization of the immune response was evaluated. Morphofunctional changes in the thyroid gland in animals with the central and peripheral mechanisms of the development and regression of the nonthyroid disease syndrome were detected.

Inhibitory effect of aluminium on calcium absorption in small intestine of rats with different thyroid hormone status

To analyse the influence of thyroid status on the effect of aluminium (Al) upon intestinal calcium (Ca) absorption, adult male Wistar rats with experimentally altered thyroid hormones circulating levels, were orally treated (o.g.) with 0 (control), or 50 mg elemental Al (as chloride)/kg body weight (b.w.) per day, for a 14 d period. Hyper- and hypo-thyroid conditions were respectively achieved by means of administration of either sodium levothyroxine (50 microg/kg b.w. per day, o.g.) or methimazole, a thyroxine synthesis inhibitor (1mg/kg b.w. per day, o.g.). In duodenum-jejunum segments, in vitro mucosa-to-serosa (45)Ca flux (JCa(ms)) and kinetics of (45)Ca uptake in isolated enterocytes, were determined. In serum, concentrations of thyroxine (T4) and triiodothyronine (T3) were measured by chemiluminescent enzyme immunoassay. Unlike non-Al-treated rats, JCa(ms) of Al-exposed rats decreased as serum levels of T4 and T3 increased, showing a significant inverse correlation in both cases (T4: r(2)=0.414, P=0.024; T3: r(2)=0.443, P=0.018). Enterocytes isolated from rats treated with Al plus thyroxine showed a reduction of both maximum Ca uptake (4.86+/-0.44 vs. 6.85+/-1.04 nmol Ca/mg protein, P<0.05) and K(m) (0.84+/-0.18 vs. 1.05+/-0.36 mM, P<0.05) when compared to control. The observed variability in the Al effect on Ca transport with thyroid status of rats could be reflecting a negative interaction of Al with thyroid hormone action mechanisms on intestinal Ca absorption, which would take place mainly at Ca entry into enterocyte from lumen.

Effects of dietary curcumin on thyroid status in rats

Effects of dietary curcumin on thyroid status in rats

Negative bias from analog methods used in the analysis of free thyroxine in rat serum containing perfluorooctanesulfonate (PFOS)

Decreases in serum total thyroxine (TT4) and free thyroxine (FT4) without a compensatory rise in thyroid stimulating hormone (thyrotropin or TSH) or histological changes of the thyroid have been observed in studies with perfluorooctanesulfonate (PFOS) treatments in rats. Prior observations do not fit the clinical profile of a hypothyroid state. PFOS is known to compete with fatty acids for albumin binding, and serum free fatty acids (FFA) are known to interfere with FT4 measurement using analog methods due to competition for protein binding. Therefore, we hypothesized that measured decreases in serum FT4 by analog methods in the presence of PFOS were due to carrier protein binding interference. We compared FT4 analog assay methods with a reference method using equilibrium dialysis (ED-RIA) for FT4 measurement in rat sera in vitro and in vivo. We also measured hepatic malic enzyme mRNA transcripts and activity as a marker for hepatic thyroid hormone response. PFOS did not reduce serum TT4 and FT4 in vitro at concentrations up to 200 μM. After three daily 5 mg/kg oral doses of potassium PFOS to female rats, serum TSH and FT4 by ED-RIA were unchanged (although FT4 determined by two common analog methods was decreased), and malic enzyme was not suppressed. These data suggest that prior reports of reduced free thyroid hormone in the presence of PFOS were due to negative bias in analog methods and that short-term PFOS treatment does not suppress the physiological thyroid status in rats. A reference method such as ED-RIA should be used for determination of serum FT4 in the presence of PFOS.

Effects of 5, 5'-diphenylhydantoin on the thyroid status in rats.

Treatment of rats with phenytoin (DPH), an anti-epileptic drug, results in lower tissue thyroid hormone (TH) levels. To investigate if this is accompanied by tissue hypothyroidism, rats were treated for 3 weeks with DPH (50 mg/kg body wt in food). Thyroid hormone-dependent parameters were measured, and the results were compared to those of control rats and to those of athyreotic rats substituted with thyroxine + triiodothyronine (Tx + TH) to reach the same plasma TH levels as DPH-treated rats. These rats were mildly hypothyroid with regard to their TH and TSH levels and TH-dependent parameters. Both DPH and Tx + TH led to a decrease in plasma thyroxine (T4) and triiodothyronine (T3) (+/-70% of the control). The percentage free T4 was unchanged. Plasma thyrotropin (TSH) was increased only in the Tx + TH rats (sixfold). For DPH rats, pituitary hormone content was not different from the control; growth hormone was lower and TSH was higher in Tx + TH rats. In DPH and Tx + TH rats, an increase in hepatic T4 and T3 uridine-diphosphate glucuronyltransferase activity was found, likewise indicating a change in the metabolic pathway of TH. Hepatic iodothyronine deiodinase (ID) type I activity decreased in Tx + TH rats but did not alter in DPH rats. Hepatic alpha-glycerophosphate dehydrogenase (alpha-GPD) decreased in DPH and Tx + TH rats. Malic enzyme in liver was enhanced in DPH rats. In the brains of DPH rats the level of alpha-GPD activity was raised; in Tx + TH it was lowered. The ID type II activity in the brain was reduced in DPH rats, but ID type III did not change for either group. Total body oxygen consumption increased in DPH rats (13%); it decreased in Tx + TH rats (9%). Our results show that DPH causes changes comparable to mild hypothyroidism. The lack of or a diminished hypothyroid response can be explained as the attenuating agonistic effect of DPH, which is supported by O2 consumption, brain ID type II and alpha-GPD activities. The T4 content was reduced by 30% in thyroid digests; this, together with a reduced T4 secretion, can lead to serious hypothyroxinemia during prolonged DPH treatment.

Hepatic indices of thyroid status in rats treated with hexachlorobenzene.

The functional thyroid status of hexachlorobenzene (HCB)-treated rats was studied. HCB caused a depletion of serum thyroxine (T4), but did not change L-3,5,3'-triiodothyronine (T3) levels in serum of rats. The activities of the thyroid regulated mitochondrial enzyme L-glycerolphosphate dehydrogenase (LGPD) and cytosolic enzymes, malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were assayed in livers of normal and HCB (100 mg/100 g bw) treated Wistar rats. Mitochondrial LGPD activity did not change significantly, however ME, 6GPD and G6PD were induced by HCB only in non-thyroidectomized animals. The absence of cytosolic enzymes induction in thyroidectomized rats treated with HCB indicates that HCB is not intrinsically thyromimetic. The induction of hepatic ME, G6PD and 6PGD activities in HCB thyroidectomized rats was dependent on the presence of thyroid hormone. The unchanged activity of mitochondrial LGPD in contrast to the increased activities of the cytosolic enzymes ME, G6PD and 6PGD is not consistent with a shift in functional thyroid status following HCB treatment.

Different responses between thyroxine 5′-monodeiodinase and protein disulfide isomerase activities to dietary fat and thyroid status in rat liver

On the hypothesis that rat hepatic microsomal type I iodothyronine 5′-monodeiodinase (MDI) would be identical to hepatic protein disulfide isomerase (PDI) (Boado et al. Biochem. Biophys. Res. Commun. 155 1297– 1304 (1988)), we examined the responses of these enzyme activities to dietary fat and thyroid status in rats. The hepatic MDI activity was higher in rats fed high fat diet than in rats fed low fat diet, but the hepatic PDI activity showed the reverse responses to the diets. Propylthiouracil administration (hypothyroidism) lowered the MDI activity, but elevated the PDI activity. Thyroxine administration (hyperthyroidism) elevated the MDI activity but had no effect on the PDI activity. These results indicate that the two enzyme activities are regulated by different mechanisms in vivo , suggesting that MDI and PDI are not identical enzymes.

Effects of perfluorodecanoic acid on hepatic indices of thyroid status in the rat

Perfluorodecanoic acid (PFDA) alters the circulating level of thyroid hormones, but the physiological significance of this change at the target tissue remains to be defined. To this end, the activities of thyroid-responsive hepatic enzymes were examined in adult male rats 1 week after treatment with a single dose of PFDA (20, 40 or 80 mg/kg). Since PFDA treatment caused a dose-related reduction in feed intake, vehicle-treated rats pair-fed to their counterparts receiving PFDA were used to determine if any of the PFDA-induced alterations in enzyme activity were secondary to hypophagia. Following the administration of PFDA, l-glycerol-3-phosphate dehydrogenase, a liver mitochondrial enzyme sensitive to thyroid status, exhibited a modest increase in activity, whereas that of succinate dehydrogenase, a constitutive mitochondrial marker enzyme, was similar in both PFDA-treated rats and their pair-fed counterparts at all dose levels examined. Activity of cytosolic lactate dehydrogenase was also augmented modestly in livers of rats receiving PFDA. In contrast, activity of cytosolic malic enzyme, a thyroid-responsive enzyme, was increased markedly in PFDA-treated rats. Hepatic activity of glucose-6-phosphate dehydrogenase, which also responds to alterations in thyroid status, exhibited a modest increase with 20 and 40 mg/kg PFDA but was similar in both PFDA-treated rats and their pair-fed counterparts at the 80 mg/kg dose level. Absolute and relative liver mass was elevated in PFDA-treated rats at all dose levels in comparison to the appropriate vehicle-treated pair-fed animals. Total hepatic content of DNA was maintained in PFDA-treated rats at all dose levels, whereas a significant decrease in liver DNA was found in the vehicle-treated rats pair-fed to animals receiving 80 mg/kg PFDA. Following administration of PFDA, protein content per total liver was similar to that of their pair-fed counterparts. Thus, the pattern of activity of thyroid-responsive hepatic enzymes was not compatible with a functional shift toward a lessened thyroid status in rats treated with PFDA.

Effects of perfluorodecanoic acid on thyroid status in rats

Treatment of rats with toxic doses of perfluorodecanoic acid (PFDA) results in reduction in feed intake, body weight, serum thyroxine (T 4) and triiodothyronine (T 3) concentrations, resting heart rates, and body temperatures. Some of these effects resemble changes characteristic of hypothyroidism. Therefore the effects of PFDA on functional thyroid status were examined to relate changes in thyroid status with signs of PFDA toxicity. In the present study, the dose-related effects of PFDA on plasma thyroid hormone concentrations and a number of indices of thyroid status were investigated and compared with signs of PFDA toxicity. Young adult male Sprague-Dawley rats were given single intraperitoneal doses of PFDA (20, 40, or 80 mg/kg), and subsequent changes were evaluated 7 days after dosing. Decreases in body weight and feed intake were used as measures of PFDA toxicity and ranged from minimal to severe. Plasma T 4 concentrations and free thyroxine index were drastically reduced at all doses, and these changes were mimicked by pair feeding only at the high dose of PFDA (80 mg/kg). Plasma T 3 concentrations were not affected by PFDA treatment, whereas pair feeding at the high-dose level (80 mg PFDA/kg) resulted in a significant reduction (ca. 50% from unlimited-fed control) in T 3. Although PFDA caused a dose-dependent decrease in thyroid gland weight which was not completely paralleled by pair feeding, thyroid histology was unremarkable. PFDA treatment resulted in a small decrease in basal metabolic rate (8% at 80 mg PFDA/kg). A greater reduction (ca. 18%) in basal metabolic rate was observed in vehicle-treated controls pair-fed to rats of the 80 mg PFDA/kg dose group. Thermogenesis, as measured by oxygen consumption and body core temperatures, was not greatly affected by PFDA treatment, and these changes were paralleled by pair feeding. Reductions in plasma T 4 concentration and free thyroxine index at a low dose of PFDA (20 mg/kg) indicate that PFDA-induced hypothyroxinemia can be dissociated from its overtly toxic effects (i.e., severe hypophagia and body weight loss) observed at higher doses. The results obtained here suggest that despite alterations in plasma thyroid hormone levels there is no consistent pattern of effects on functional thyroid status which could explain the overt toxicity of PFDA.

Hepatic indices of thyroid status in rats treated with 2,3,7,8-tetrachlorodibenzo- p-dioxin

The functional thyroid status of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD)-treated rats is unknown. Therefore, activities of certain thyroid-responsive enzymes were examined in the livers of adult male Sprague-Dawley rats 1 week after treatment with TCDD (6.25, 25 or 100 μg/kg). Activity of the thyroid-responsive flavin L-glycerol-3-phosphate dehydrogenase (per mg mitochondrial protein) was decreased slightly in livers of TCDD-treated rats, while that of succinate dehydrogenase remained unchanged. In contrast, activities (per mg supernatant protein) of three thyroid-responsive NADP-dependent cytosolic enzymes, malic enzyme, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, were increased by TCDD treatment in a dose-dependent manner. Lactate dehydrogenase (activity per mg supernatant protein) was also augmented slightly 1 week after TCDD administration. Liver mass was increased by TCDD treatment in a dose-dependent manner, but DNA content per liver was similar at all doses examined. Total hepatic protein, expressed per liver or mg hepatic DNA, was increased in TCDD-treated rats when compared to their pair-fed counterparts. The decreased activity of the mitochondrial l-glycerol-3-phosphate dehydrogenase, in contrast to the increased activities of the supernatant enzymes, malic enzyme, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, is not consistent with a shift in functional thyroid status following TCDD treatment.

Metabolic Rate and Thyroid Status in Rats Fed Diets of Different Protein-Energy Value: The Importance of Free T3

Oxygen consumption and thyroid hormone status have been investigated in relation to dietary protein and energy intake in young growing rats fed a control diet of 18% protein as well as diets containing 9 and 4.5% protein fed ad libitum and an 18% protein diet fed at a restricted intake for up to 14 days. Measurements of growth rate, food intake and oxygen consumption indicated that the rats fed a 4.5% protein diet ad libitum and those fed restricted amounts of an 18% protein diet have behaved similarly with severely arrested growth and reduced rates of oxygen consumption and food intake. However, the rats fed the 9% protein diet ad libitum differed from the control group only in terms of a reduced growth rate. Among all the rats thyroid hormone status was associated with the metabolic rate only in the case of the concentration of free L-3,3′,5-triiodothyronine (T3), which was reduced in the groups fed 4.5% protein and 18% protein (restricted). Total T3 was actually increased in the rats fed 9% and 4.5% protein and unchanged in the restricted group. These differences in the concentrations of free and total T3 appeared to reflect the fact that the binding capacity for T3 increased with decreasing levels of dietary protein. It is concluded therefore that measurement of free rather than total T3 is the appropriate index of physiological thyroid status in protein-energy malnutrition, at least in the rat.