Euthyroid Ones Research Articles

Cognition Deficit and Hypothyroidism in a Population-Based Study of Iranian Women

Background: There are some evidences on adverse effects of reducing thyroid hormones levels on appearing cognition. The present study aimed to assess cognitive function in patients with hypothyroidism under-treated with routine hormone replacement therapy compared to healthy euthyroid individuals. Methods: Thirty consecutive hypothyroid female patients aged 25 to 40 years who referred to endocrinology and metabolism clinic at Rasoul-e-Akram hospital in Tehran within a four-year period in 2015 were assessed. Also, thirty healthy euthyroid subjects matched for sex, age, and educational level were selected as the control. For assessment of cognitive function status, the Mini Mental Status Exam (MMSE) was used. Results: The study showed lower mean cognitive score in hypothyroid patients when compared to euthyroid ones (25.33 ± 3.90 versus 29.40 ± 1.80, p = 0.010). Regarding association between cognition deficit and patients’ baseline characteristics, except for educational level that was positively associated with cognition score (p < 0.001), no significant association was revealed between mean cognition score and other parameters including age (p = 0.569), occupation status (p = 0.631), and marital status (p = 0.859). According to the Bonferroni correction analysis, lower cognitive function was revealed in those with primary educational levels than those who with college degrees. Conclusion: Clinical hypothyroidism is potentially association with cognition deficit especially in those with lower educational level.

SERUM ZONULIN LEVELS IN HYPOTHYROID AND EUTHYROID PATIENTS WITH HASHIMOTO'S THYROIDITIS - A PILOT STUDY.

Human zonulin is a protein that regulates the intercellular tight junctions in various tissues and organs of the human body. Hashimoto's thyroiditis (HT) is one of the most common endocrine autoimmune disorder, but the role of increased intestinal permeability in its pathogenesis is still being studied. This pilot cross-sectional study investigates serum zonulin concentration in adults with Hashimoto's thyroiditis and assesses the relationship between zonulin levels, clinical hormonal and immunological characteristics. A group of 62 adults with HT participated in this study and were divided into three groups: hypothyroid (n=33) euthyroid (n=25) and hyperthyroid (n=4). Serum zonulin was determined using an ELISA method. Age, gender and BMI were different between groups (hypothyroid and euthyroid ones). Serum zonulin values ranged from 2.6 to 198.0 ng/mL in participants. A direct positive correlation was found between serum zonulin levels and weight and BMI (r = 0.351, p = 0.008 and r = 0.236, p = 0.05, respectively). There is no correlation between zonulin and thyroid hormones or autoantibodies in Hashimoto thyroiditis patients. There is a difference in zonulin levels between the studied groups, but they are not statistically significant.

Modulation of glutamate levels and Na+,K+-ATPase activity contributes to the chrysin memory recovery in hypothyroidism mice

Abnormalities in the thyroid hormones, like in hypothyroidism, are closely related to dementia and Alzheimer's disease demonstrating the main symptom of these disorders: memory deficit. In this study we evaluated the effect of chrysin on deficit spatial and aversive memories and the contribution of glutamatergic, cholinergic pathways and Na+, K+-ATPase activity on hippocampus and prefrontal cortex in hypothyroid adult female mice C57BL/6. Hypothyroidism was induced by the continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. The exposure to MTZ was associated to low plasma levels of thyroid hormones (TH) compared to the control group on the 32nd. Subsequently, euthyroid and MTZ-induced hypothyroid mice received (intragastrically) either vehicle or chrysin (20 mg/kg) once a day for 28 consecutive days. After treatments mice performed the following behavioral assessments: open-field test (OFT), morris water maze (MWM) and passive avoidance test. Additionally, plasma TH levels were measured again, as well as glutamate levels, Na+,K+-ATPase and acetylcholinesterase (AChE) activities were analyzed in the hippocampus and prefrontal cortex of mice. Mice with hypothyroidism showed a deficit of spatial and aversive memory and chrysin treatment reversed these deficits. It also reduced the levels of glutamate and decreased Na+,K+-ATPase activity in both cerebral structures in the hypothyroid mice compared with the euthyroid ones, with the exception of glutamate in the hippocampus, which was a partial reversal. AChE activity was not altered by treatments. Together, our results demonstrate that chrysin normalized hippocampal glutamate levels and Na+,K+-ATPase activity, which could be involved in the reversal of memory deficit.

Exercise training improves quality of life in women with subclinical hypothyroidism: a randomized clinical trial.

The aim was to evaluate the quality of life (HRQoL) in women with subclinical hypothyroidism (sHT) after 16 weeks of endurance training. In the first phase, a cross-sectional study was conducted in which 22 women with sHT (median age: 41.5 (interquartile range: 175) years, body mass index: 26.2 (8.7) kg/m2, thyroid stimulating hormone > 4.94 mIU/L and free thyroxine between 0.8 and 1.3 ng/dL were compared to a group of 33 euthyroid women concerned to HRQoL. In the second phase, a randomized clinical trial was conducted where only women with sHT were randomly divided into two groups: sHT-Tr (n = 10) - participants that performed an exercise program - and sHT-Sed (n = 10) - controls. Exercise training consisted of 60 minutes of aerobic activities (bike and treadmill), three times a week, for 16 weeks. The HRQoL was assessed by the SF-36 questionnaire in the early and at the end of four months. Women with sHT had lower scores on functional capacity domain in relation to the euthyroid ones (770 ± 23.0 vs. 88.8 ± 14.6; p = 0.020). The sHT-Tr group improved functional capacity, general health, emotional aspects, mental and physical component of HRQoL after training period, while the sHT-Sed group showed no significant changes. After 16 weeks of aerobic exercise training, there were remarkable improvements in HRQoL in women with sHT.

Thyroid function and autoantibody status in Bangladeshi patients with type 2 diabetes mellitus

Background: Thyroid dysfunction is common in patients with type 2 diabetes mellitus (T2DM), and data on thyroid autoimmunity in T2DM are scarce. This study was designed to observe the frequency of thyroid dysfunction and autoimmune thyroid disease in Bangladeshi T2DM patients. Materials and Methods: In this cross-sectional study, we investigated 1056 T2DM patients with unknown thyroid function status throughout the country. Serum thyroid stimulating hormone (TSH) and free T4 (FT4) and antithyroid antibodies (antithyroid peroxidase or antimicrosomal) were measured. Statistical analysis was done using IBM SPSS Statistics for Windows, version 23.0 software. P ≤ 0.05 was considered statistically significant. Results: The observed frequency of thyroid dysfunction in our study was 21.9% (subclinical hypothyroid 14.1%, primary hypothyroid 4%, subclinical hyperthyroid 1.9%, overt hyperthyroid 1%, and secondary hypothyroid 0.9%). 32.9% of the participants were positive for thyroid autoantibodies. The patients with thyroid dysfunction had a higher body mass index (BMI), higher TSH, lower FT4, and higher thyroid autoantibody titer than euthyroid ones. Thyroid dysfunction was more common in females and autoantibody-positive individuals. TSH had an inverse negative correlation with FT4 in both euthyroid and thyroid dysfunction groups and had a positive correlation with age in the euthyroid group only. FT4 had an inverse correlation with age and duration of diabetes in both groups and with BMI in euthyroid diabetic patients. Conclusion: Thyroid dysfunction and autoimmunity are common in Bangladeshi T2DM patients. Thyroid dysfunction was more common in females and autoantibody-positive diabetic patients.

Role of Thyroid Deficiency on Adiponectin, Leptin, and Metabolic Status in Visceral Obesity: A Cross-Sectional Study.

AbstractHypothyroidism results in disturbances of metabolism influencing many regulatory systems and active molecules as adipocytokines. Objective of the study was to investigate leptin and adiponectin in patients with visceral obesity and hypothyroidism in relation to metabolic status, insulin resistance and systemic inflammation. A total of 118 patients (59 hypothyroid and 59 euthyroid) were enrolled divided into four age-matched groups according to body wеight (BMI) and thyroid function. Laboratory panel includes TSH, FT4, FT3 (CMIA), adiponectin and leptin (ELISA), IL- 6 (ECLIA), CRP, insulin, glucose, apolipoprotein B and lipoprotein (a) - Lp(a). Hypothyroid patients revealed significant positive correlations of TSH, adiponectin and Lp(a). Their medians of 10.4 mU/l, 12.5 µg/ml and 116.3 mg/l respectively were significantly higher than in euthyroid patients- 1.5 mU/l, 6.26 µg/ml and 32.0 mU/l (p < 0.0001). Leptin in both obese groups was significantly higher than in patients with normal weight. Leptin in hypothyroid patients was lower but not significant to euthyroid ones (9.7 ng/ml vs 13.4 ng/ml respectively, p = 0.16), correlated negatively to TSH and positively to CRP, IL-6, ApoB, Lp(a) and BMI. HOMA-IR and serum insulin at 120 min in OGTT were significantly higher in hypothyroid than in euthyroid patients independent of BMI (p < 0.001). Adiponectin, insulin resistance and chronic inflammation indices in hypothyroid patients correlated positively to TSH, BMI and atherogenic lipoproteins subclasses ApoB/Lp(a). Increased adiponectin in thyroid deficiency could be due to secondary resistance of adiponectin receptors or appeared as a compensatory pathogenetic factor in hypothyroidism.

Depression and Hypothyroidism in a Population-Based Study of Iranian Women.

Recent biochemical and physiological investigations have focused on the fundament of mood disorders in thyroid dysfunction. The present study aimed to address depressive disorder in a sample of Iranian hypothyroid women compared to euthyroid individuals. Thirty consecutive hypothyroid female patients aged 25 to 40 years who referred to the Endocrinology and Metabolism Clinic at Rasoul-e-Akram Hospital in Tehran within a four-month period in 2015 were assessed. Thirty healthy euthyroid subjects matched for sex, age, and educational level were selected as the control. For assessment of depression status, Depression Anxiety Stress Scale-21 (DASS-21) was employed. The study showed higher mean depression score in hypothyroid patients when compared to euthyroid ones (13.8 ± 9.5 versus 5.8 ± 5.2, p = 0.010). No significant association was revealed between mean depression score and patients' education level (p = 0.627), age (p = 0.967), occupation status (p = 0.211), and marital status (p = 0.556). Hypothyroid women are predisposed to depressive symptoms independent of their baseline demographic and socioeconomic characteristics.

Experimentally induced hyperthyroidism influences oxidant and antioxidant status and impairs male gonadal functions in adult rats.

The objective of the present experiment was to study the effect of hyperthyroidism on male gonadal functions and oxidant/antioxidant biomarkers in testis of adult rats. Induction of hyperthyroidism by L-thyroxine (L-T4, 300 μg kg(-1) body weight) treatment once daily for 3 or 8 weeks caused a decrease in body weight gain as well as in absolute genital sex organs weight. The epididymal sperm counts and their motility were significantly decreased in a time-dependent manner following L-T4 treatment. Significant decline in serum levels of luteinising hormone, follicle stimulating hormone and testosterone along with significant increase in serum estradiol level was observed in hyperthyroid rats compared with euthyroid ones. Significant increase in malondialdehyde and nitric oxide concentration associated with significant decrease in superoxide dismutase and catalase activity was also noticed following hyperthyroidism induction. Both reduced glutathione content and glutathione peroxidase activity were increased in hyperthyroid rats compared with control rats. Marked histopathological alterations were observed in testicular section of hyperthyroid rats. These results provide evidence that hypermetabolic state induced by excess level of thyroid hormones may be a causative factor for the impairment of testicular physiology as a consequence of oxidative stress.

Effect of thyroid dysfunction on hemoglobin A1c in polycystic ovary patients during ovulation induction trials.

Background: Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders leading to infertility. Majority of women with PCOS have insulin resistance and elevated hemoglobin A1c.The presence of thyroid dysfunction may affect the levels of HbA1c and the results of ovulation induction programs. 
 Objectives: To evaluate the level of serum hemoglobin A1c according to the type of thyroid dysfunction in polycystic ovary patients during ovarian stimulation trials. 
 Patients and Methods: Eighty three polycystic ovary patients were enrolled in this study, attending the infertility clinic in Al-Yarmouk Teaching Hospital, in the period between November 2012 and May 2013. After thorough history and examination blood samples were withdrawn for the estimation of LH, FSH, testosterone, prolactin, TSH, T3, T4 and A1C in day 2 or 3 of the menstrual cycle, Progesterone was determined in day 21 of the cycle. Ultrasound was done also at cycle day 3 for antral follicles measurements. After diagnosing PCOS the patients were divided into 3 groups, euthyroid group (control), hypothyroid and hyperthyroid groups. Ovulation induction treatment was given and ultrasound was done at the day of hCG injection. 
 Results: There was no significant difference between control and patients groups regarding age (26.31 ± 5.04 Vs 27.17 ± 5.76) and BMI (31.7 ± 5.69Vs 29.25 ± 6.28).HbA1c level was significantly different between the control and patients group with a significant positive correlation between HbA1c and TSH. In clomiphene citrate treated groups, Hb A1c level, the number of antral follicles and the size of follicles at day of hCG injection were not significantly different between the patients and control groups. 
 Conclusions: HbA1c level is significantly affected by thyroid dysfunction in PCOS patients as it is higher in the Hypothyroid group and lower in the Hyperthyroid group. Using Clomiphene citrate in PCOS does not significantly increase the mean size of follicles after ovarian stimulation in patients with thyroid dysfunction from that in Euthyroid ones.

The Effects of Hypothyroidism on the Mechanical Properties and Histomorphological Structure of the Thoracic Aorta

This experimental study investigates the effects of hypothyroidism on the descending thoracic aorta. Hypothyroidism was induced in 20 male Wistar rats by administering 0.05% of 6-n propyl 2-thiouracil (PTU) in their drinking water for 8 weeks. Euthyroid rats were used as controls. Animals were sacrificed and longitudinal strips of the descending aorta were subjected to various preselected levels of stress in a uniaxial tensile-testing device. Analysis of stress-strain, elastic modulus-strain curves disclosed significant differences between groups, indicative of stiffer aortas in hypothyroid animals at the upper physiologic and higher levels of pressure. Remodeling of the aortic wall of hypothyroid animals revealed significant histological changes. The thoracic aorta of hypothyroid rats compared with that of euthyroid ones became stiffer at high strains, including the upper physiologic range, loosing part of its distensibility. Hypothyroidism was also associated with diameter enlargement and substantial lengthening of the aorta.

An “inexplicable” problem of habitual abortion

Thyroid autoimmunity (TAI) appears to be a determining factor in pregnancy loss. Many studies have confirmed this association, not only in hypo- and hyperthyroid women but also in euthyroid ones. The main risk associated with TAI is the occurrence of maternal hypothyroidism, with its potential deleterious effects for both the mother and fetus. We report a case of a 35-years-old woman with a history of habitual abortion. After diagnosis of TAI with normal thyroid function and treatment with levothyroxine, the patient became pregnant. After a normal pregnancy without problems, she gave birth of normal fetus at 39’ weeks gestation.

Subclinical hypothyroidism: psychiatric disorders and symptoms

To evaluate the prevalence of psychiatric disorders and symptoms in patients with subclinical hypothyroidism. Ninety-four outpatients with at least two elevated serum thyrotrophin levels (> 4 microU/ml) and normal FT4, and 43 euthyroid outpatients, both groups from HUCFF-UFRJ, were evaluated. Psychiatric diagnosis was based on the Structured Clinical Interview Diagnostic for the DSM-IV axis I (SCID-I/DSM-IV), the psychopathological symptoms on Hamilton anxiety and depression scales, and the Beck Inventory. Our data showed an increased prevalence of psychiatric disorders in the subclinical hypothyroidism patients when compared to the euthyroid group (45.7% vs 25.6%; p = 0.025), mood disorders being the most frequent. The prevalence of depressive symptoms based on Beck's Scale among subclinical hypothyroidism patients was about 2.3 times higher than among euthyroid ones (45.6% vs 20.9%, p = 0.006). Anxiety symptoms were also more frequent among subclinical hypothyroidism patients (87.0% vs 60.5%, p < 0.001), mainly clinical anxiety (44.6% vs 23.3%; p = 0.001). Our results showed a significant association of subclinical hypothyroidism with psychiatric disorders and an increased frequency of subsyndromic depression and anxiety symptoms in subclinical hypothyroidism in relation to the euthyroid group.

The Mechanical Performance and Histomorphological Structure of the Descending Aorta in Hyperthyroidism

Thyroid hormones decrease systemic vascular resistance by directly affecting vascular smooth muscle relaxation. There is limited literature about their effect on the mechanical performance of the aortic wall. Therefore, the authors determined the influence of hyperthyroidism on the mechanical properties and histomorphological structure of the descending thoracic aorta in rats. Severe hyperthyroidism was induced in 20 male Wistar rats by administering L-thyroxine (T(4)) in their drinking water for 8 weeks; age-matched normal euthyroid rats acted as controls. Animals were sacrificed, and the mechanical and histomorphometrical characteristics of the descending thoracic aorta were studied. The aortic wall of hyperthyroid rats was stiffer than that of euthyroid animals at the upper physiologic levels of stress or strain (p < 0.05) but less stiff at the lower physiologic and lower levels (p < 0.05). The aorta of hyperthyroid animals compared with that of euthyroid ones showed an increase of the internal and external diameters (p < 0.05), the media area (p < 0.05), the number of smooth muscle cell nuclei (p < 0.05), and the collagen density (p < 0.05) and a decrease in the elastin laminae thickness (p < 0.001) and elastin density (p < 0.001). In hyperthyroid rats, the aortic wall was stiffer at the upper physiologic and higher levels of stress and strain. These changes correlated with microstructural changes of the aortic wall. The coexistence of hyperthyroidism with disease states or clinical conditions that predispose to increased arterial pressure may be associated with increased arterial stiffness and have undesirable consequences on the mechanical performance of the thoracic aorta and hemodynamic homeostasis. These changes could lead to an increased risk for developing vascular complications.

Influence of hyperthyroidism on the effect of adenosine transport blockade assessed by a novel method in guinea pig atria

The aim of the present study was to investigate the effect of hyperthyroidism on the trans-sarcolemmal adenosine (Ado) flux via equilibrative and nitrobenzylthioinosine (NBTI)-sensitive nucleoside transporters (ENT1) in guinea pig atria, by assessing the change in the Ado concentration of the interstitial fluid ([Ado]ISF) under nucleoside transport blockade with NBTI. For the assessment, we applied our novel method, which estimates the change in [Ado]ISF utilizing the altered inotropic response to N6-cyclopentyladenosine (CPA), a relative stable selective agonist of A1 Ado receptors, by providing a relative index, the equivalent concentration of CPA. Our results show an interstitial Ado accumulation upon ENT1 blockade, which was more extensive in the hyperthyroid samples (CPA concentrations equieffective with the surplus [Ado]ISF were two to three times higher in hyperthyroid atria than in euthyroid ones, with regard to the negative inotropic effect of CPA and Ado). This suggests an enhanced Ado influx via ENT1 in hyperthyroid atria. It is concluded that hyperthyroidism does not alter the prevailing direction of the Ado transport, moreover intensifies the Ado influx in the guinea pig atrium.

Effect of experimental hypo- and hyperthyroidism on serum adiponectin

Adiponectin, an adipocyte-derived hormone, has been shown to decrease body weight by increasing thermogenesis and lipid oxidation. Thyroid hormones have similar effects. Here we investigated if experimental hypo- and hyperthyroidism in rats would induce changes in serum adiponectin concentration. Adult rats became hypothyroid by treatment with 0.03% methimazole in the drinking water for 28 days or hyperthyroid by subcutaneous thyroxine injections (50 μg/100g body weight) for 10 days. Serum adiponectin level of hyperthyroid rats was 3.2-fold higher than that of euthyroid ones ( P < .001), whereas that in hypothyroid rats tended to be lower (38%), but without statistical significance. Serum adiponectin had a positive correlation with serum thyroxine ( r = .81, P < .001) and triiodothyronine ( r = 0.68, P = .03) and a negative correlation with serum thyroid-stimulating hormone ( P = −.62, r = 0.015). In addition, there was a negative correlation between serum adiponectin level and total visceral white adipose mass (= sum of inguinal, epididymal, and retroperitoneal depots; r = −0.43; P = .032), which was reduced by 40.5% in hyperthyroid ( P < .01) but not in hypothyroid animals. A positive association between serum adiponectin level and brown adipose tissue mass was found ( r = 0.43, P = .03), but not with body weight, which was reduced in both hypo- and hyperthyroid groups. Adiponectin has been reported to have an insulin-sensitizing effect. However, in hyperthyroid rats, higher serum adiponectin level was not accompanied by statistically different changes in basal serum insulin levels, blood glucose concentrations, or glucose tolerance as compared with euthyroid rats, except for a slight increase in blood glucose level at 120 minutes after glucose intraperitoneal administration ( P < .05). Therefore, experimental hypothyroidism did not change serum adiponectin concentration, whereas hyperthyroidism induced an important elevation in the serum hormone concentration, with still unknown biological significance.

Reduction in oxidative stress and cell death explains hypothyroidism induced neuroprotection subsequent to ischemia/reperfusion insult

Hypometabolic state following hypothermia is known to protect tissues from ischemic injury. Hypothyroidism produces a hypometabolic state. The present study was undertaken to investigate the protective effects of hypothyroidism following cerebral ischemia and to ascertain the underlying mechanism. Euthyroid (E) and hypothyroid (H) animals were exposed to a 2 h of middle cerebral artery occlusion followed by 24 h of reperfusion (I/R). Specific enzymatic methods and flowcytometry were used to assess the quantitative changes of molecules involved in neuronal damage as well as in protection. As compared to euthyroid ischemic reperfused (E + I/R) rats, H + I/R rats had insignificant neurological deficit, and smaller area of infarct. H + I/R rats had significantly lower markers of oxidative stress, and lactate dehydrogenase (LDH) activity (a marker for necrosis). Natural antioxidant activity (particularly superoxide dismutase) and integrity of mitochondria (membrane potential) were maintained in H + I/R group but not in E + I/R group. The number of neurons undergoing apoptosis significantly lower in hypothyroid ischemic rats as compared to euthyroid ones. These results suggest that hypothyroid animals face ischemia and reperfusion much better compared to euthyroid animals. A possible explanation could be the decreased oxidative stress and maintained antioxidant activity that finally leads to a decrease in necrosis and apoptosis. These observations may suggest strategies to induce brain-specific downregulation of metabolism that may have implications in the management of strokes in human beings.

Effect of 3,5-diiodo-L-thyronine on thyroid stimulating hormone and growth hormone serum levels in hypothyroid rats

We have investigated the biological effects of physiological doses of 3,5-diiodo-L-thyronine (3,5-T2) and 3,3′-diiodo-L-thyronine (3,3′-T2) (at doses from 2.5 to 10 μg/100 g BW) on serum TSH and GH levels in rats made hypothyroid by propylthiouracil and iopanoic acid administration. In such animals deiodinase activities were inhibited and thyroid hormones serum levels strongly reduced. The effects of T2s were compared with those elicited by 3,5,3′-triiodo-L-thyronine (T3) (2.5 μg/100 g BW).The serum TSH level was much greater in hypothyroid rats than in euthyroid ones. T3 administration suppressed TSH by 88% compared to control (i.e, the level in hypothyroid rats); it thus reached a value not significantly different from that seen in the euthyroid rats. 3,5-T2 produced a similar effect, suppressing the TSH level by about 75% compared to control, it thus reached values not significantly different from those of the euthyroid and T3-treated rats. By contrast, 3,3′-T2 had no effect on TSH, whatever the dose. The serum GH level was much lower in hypothyroid rats than in euthyroid ones. T3 administration increased the GH level by about 5-fold, restoring it to the value seen in euthyroid rats. 3,5-T2-treated hypothyroid rats, at all the doses used (from 2.5 to 10 μg/100 g BW), showed increased serum GH levels: at a dose of 10 μg/100 g BW the level reached a value about 5-fold higher than that in hypothyroid rats. This value was not significantly different from those of euthyroid and T3-treated rats. 3,3′-T2 did not affect GH levels whatever the dose. Thus, 3,5-T2 (but not 3,3′-T2) seems to mimic the effects of T3 on serum TSH and GH levels in rats.

Altered endothelin 1 concentration in brain and peripheral regions during thyroid dysfunction.

Earlier studies have shown that plasma concentrations of endothelin 1 (ET-1) and the receptors for ET are altered during hyperthyroidism, while they are not affected during hypothyroidism. The present study was undertaken to determine the changes in concentration of endogenous ET-1 in various tissues of hyper- and hypothyroid rats. Hyperthyroidism was induced by daily administration of thyroxine (T4, 0.1 mg/kg, i.p.) for 8 weeks, while hypothyroidism was induced by daily administration of methimazole (10 mg/kg, i.p.) for 8 weeks. The concentration of endogenous ET-1 was determined in the brain regions (hypothalamus, corpus striatum, pituitary, hippocampus and spinal cord), heart, adrenals, kidneys and thoracic aorta using a radioimmunoassay procedure. Blood pressure and heart rate were significantly increased in hyperthyroid rats, while they were not affected in hypothyroid rats when compared with control (euthyroid) rats. Serum T4 and T3 levels were significantly increased in hyperthyroid rats, while they were significantly decreased in hypothyroid rats when compared with euthyroid rats. The concentrations of ET-1 in the hypothalamus, corpus striatum, hippocampus and spinal cord were not altered in hyper- or hypothyroid rats when compared with euthyroid rats. However, the pituitary showed a significant (p < 0.001) increase (104%) in ET-1 concentration in hyperthyroid rats when compared with euthyroid ones, while hypothyroid rats did not show any significant change in ET-1 concentration in the pituitary. In peripheral tissues ET-1 concentrations were not altered in the heart and adrenals of hyper- and hypothyroid rats when compared with euthyroid rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid hormones control lipid composition and membrane fluidity of skeletal muscle sarcolemma

Sarcolemma membrane lipid phase of skeletal muscles of hyperthyroid animals was compared to that of control (euthyroid) ones. Hyperthyroidism caused 15% decrease in cholesterol and 70% increase in the phospholipid content of the membrane. This was accompanied by the alterations in proportions between individual phospholipid classes, and was followed by changes in the composition of phospholipid fatty acids. The calculated fatty acid unsaturation index was higher for membrane lipid phase of hyperthyroid animals than of euthyroid ones. Thyroxine-induced alterations in the lipid composition of sarcolemma caused changes in the membrane fluidity and the activity of calmodulin-stimulated (Ca 2+-Mg 2+)-ATPase. Measurements of the steady-state fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene indicated that the lipid phase transition of membrane vesicles occurred at 25.9°C and at 28.9°C for preparations isolated from hyperthyroid and euthyroid rabbits, respectively. Arrhenius plot break-point temperature for CaM-stimulated (Ca 2+-Mg 2+)-ATPase activity was lower in membrane preparations isolated from hyperthyroid (26.9°C) than from euthyroid ones (30.0°C). Thus, the increase of the membrane fluidity presumably caused that the enzyme was characterized by the lower activation energy value. This phenomenon may be viewed as a supplementary mechanism for activation of the enzyme by thyroid hormones to previously reported elevation of the amount of (Ca 2+-Mg 2+)-ATPase protein exerted by hyperthyroidism (Famulski et al. (1988) Eur. J. Biochem., 171, 363–368; Famulski and Wrzosek (1988) in The Ion Pumps-Structure, Function and Regulation (Stein, W.D., ed.), pp. 355–360, Alan R. Liss, New York).

The response of rat liver lipid peroxidation, antioxidant enzyme activities and glutathione concentration to the thyroid hormone

1. 1. In liver microsomes from hyperthyroid rats NADPH-dependent lipid peroxidation induces a hydroperoxide formation 56% higher than that in euthyroid ones. 2. 2. The addition of 5 μM Fe 2+ (or Fe 3+) strongly decreases the hydroperoxide level in favour of that of TBA-reactive substances. Higher iron concentrations (30 μM) have no significant effect. 3. 3. In hepatocytes from hyperthyroid rats CCl 4-induced lipid peroxidation produces an amount of TBA-reactive substances four times higher than that in those from euthyroid rats. 4. 4. In the liver of hyperthyroid rats a GSH concentration decrease (by about 35%) is found while the opposite occurs in the blood of the same animals where GSH increases 2.5 times. 5. 5. It is shown that in the liver of hyperthyroid rats, besides higher lipid peroxidation, a more active defence mechanism is operating since both glutathione peroxidase and glutathione reductase specific activities are higher than in euthyroid rats.