Animals ; Apoptosis ; Brain/metabolism* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage/drug therapy* ; Thyroxine/pharmacology*

OBJECTIVETo observe the improvement of thyroid function and changes of Akt, p-Akt, mammalian target of rapamycin (mTOR), and para-mTOR (p-mTOR) expression in Graves' disease (GD) mice after intervened by Jiakangning Capsule (JC), and to explore possible mechanism for JC in treating GD.

METHODSGD model was established by immunizing female BALB/c mice with thyroid stimulating hormone receptor A subunit (Ad-TSHRα-289). Totally 70 successfully modeled mice were divided into the model group (n =20), the JC intervened group (n =25), the Methimazole Tablet intervened group (n =25) according to random digit table. A normal control group (n =15) and a vehicle control group (n =20, injected with Ad-null) were also set up. Mice in the JC intervened group were administered with JC suspension at the daily dose of 1. 5 g/kg by gastrogavag. Mice in the Methimazole intervened group were administered with Methimazole suspension at the daily dose of 2. 5 g/kg by gastrogavage. Equal volume of normal saline was administered to mice in the rest 3 groups by gastrogavage. All intervention lasted for 5 weeks. Six mice were selected from each group to observe pathological changes of thyroid tissues. Serum levels of thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone (TSH), and thyrotropin receptor antibody (TRAb) were analyzed by radioimmunoassay. Expression levels of Akt, p-Akt, mTOR, and p-mTOR in thyroid tissues were etermined by Western blot.

RESULTS(1) The thyroid gland in the GD model group showed proliferative changes, with enlarged follicles of various sizes. Interstitial stroma was filled with blood vessels. Structures of thyroid tissues in the JC intervened group and the Methimazole intervened group were significantly restored, and follicular hyperplasia was relieved. (2) Compared with the normal control group and the vehicle control group, levels of TRAb, T4, and T3 increased; ratios of P-Akt/β-actin, p-Akt/Akt, p-mTOR/β-actin, and p-mTOR/mTOR also increased in the model group (all P <0. 01). Compared with the model group, levels of TRAb, T4, and T3 decreased in the JC intervened group and the Methimazole intervened group (P <0. 01); ratios of p-mTOR/β-actin and pmTOR/mTOR decreased in the JC intervened group (P <0.01); ratios of P-Akt/β-actin, p-Akt/Akt, p-mTOR/β-actin, and p-mTOR/mTOR decreased in the Methimazole intervened group (P <0. 05, P <0. 01). Conclusion JC could reduce thyroid hormonc levels of GD mice and lower expression levels of mTOR, and its mechanism for improving thyroid function of GD mice might be associated with this influence.

Actins ; Animals ; Capsules ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Graves Disease ; drug therapy ; pathology ; Methimazole ; Mice ; Mice, Inbred BALB C ; Receptors, Thyrotropin ; Signal Transduction ; TOR Serine-Threonine Kinases ; Thyrotropin ; Thyroxine ; Triiodothyronine

Ammonium perchlorate (AP), mainly used as solid propellants, was reported to interfere with homeostasis via competitive inhibition of iodide uptake. However, detailed mechanisms remain to be elucidated. In this study, AP was administered at 0, 130, 260 and 520 mg/kg every day to 24 male SD rats for 13 weeks. The concentrations of iodine in urine, serum thyroid hormones levels, total iodine, relative iodine and total protein, and malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activity in thyroid tissues were measured, respectively. Our results showed that high-dose perchlorate induced a significant increase in urinary iodine and serum thyroid stimulating hormone (TSH), with a decrease of total iodine and relative iodine content. Meanwhile, free thyroxine (FT4) was decreased and CAT activity was remarkably increased. Particularly, the CAT activity was increased in a dose-dependent manner. These results suggested that CAT might be enhanced to promote the synthesis of iodine, resulting in elevated urinary iodine level. Furthermore, these findings suggested that iodine in the urine and CAT activity in the thyroid might be used as biomarkers for exposure to AP, associated with thyroid hormone indicators such as TSH, FT4.
Analysis of Variance ; Animals ; Catalase ; metabolism ; Dose-Response Relationship, Drug ; Homeostasis ; drug effects ; Iodine ; metabolism ; urine ; Male ; Malondialdehyde ; metabolism ; Perchlorates ; pharmacology ; Quaternary Ammonium Compounds ; pharmacology ; Radioimmunoassay ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Thyroid Gland ; metabolism ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood

OBJECTIVETo explore the effects of thyroid hormone on the expression of homeobox gene Nkx2.1 mRNA in child rat by supplying their hypothyroidism pregnant mother with different dose of levothyroxine (L-thyroxine, L-T(4)) in different times.

METHODS120 female Wistar rats were randomly divided into eight groups according to the body weight: control group, non-treatment hypothyroidism group, hypothyroidism groups supplied with L-T(4) in high, medium and low dosage in early stage (1st-17th day of pregnancy) and in late stage (18th day of pregnancy-20th day after childbirth). According to 100 grams of body weight, the concentrations of L-T(4) were 3.5, 2.0, 0.5 µg/d in high, medium and low dosage group. All the rats were fed with low-iodine food. The control group was given 200 µg/L potassium iodate solution as drinking water and the other groups were given deionized water. After three months, the rats were mated with normal male rats. After the pregnancy was confirmed, hypothyroidism groups were supplied with L-T(4) of different concentrations. Brain samples were taken from the 17-day fetal rats, new-born and 20-day old offsprings and the levels of Nkx2.1 mRNA in brain tissue were analyzed by real-time fluorescence quantitative PCR techniques.

RESULTSThe levels of TT(3) in hypothyroidism groups supplied with L-T(4) in high, medium and low dosages in early and late pregnant stages, non-treatment hypothyroidism group and control group were (0.85 ± 0.17), (0.81 ± 0.18), (0.86 ± 0.21), (0.85 ± 0.20), (0.89 ± 0.18), (0.85 ± 0.20), (0.86 ± 0.20), (1.08 ± 0.07) nmol/L (F = 4.08, P < 0.01); the levels of TT(4) in each group were (0.43 ± 0.16), (0.39 ± 0.11), (0.39 ± 0.13), (0.43 ± 0.17), (0.51 ± 0.19), (0.43 ± 0.16), (0.41 ± 0.15), (39.43 ± 14.16) nmol/L (F = 31.99, P < 0.01); the levels of FT(3) in each group were (3.29 ± 0.61), (3.29 ± 0.61), (3.24 ± 0.61), (3.28 ± 0.63), (3.31 ± 0.59), (3.28 ± 0.50), (3.24 ± 0.49), (4.93 ± 0.46) pmol/L (F = 5.79, P < 0.01); the levels of FT(4) in each group were (3.38 ± 0.80), (3.31 ± 0.67), (3.29 ± 0.73), (3.27 ± 0.71), (3.48 ± 0.81), (3.56 ± 0.66), (3.29 ± 0.61), (27.29 ± 4.53) pmol/L (F = 26.34, P < 0.01). The expression of Nkx2.1 mRNA in non-treatment hypothyroidism group (9.15 × 10(-5) ± 9.17 × 10(-5)) was lower than control group (65.1 × 10(-5) ± 40.90 × 10(-5)) in 17th day of pregnancy (t = 66.224, P < 0.05); the expression of Nkx2.1 mRNA in non-treatment hypothyroidism group (3.16 × 10(-5) ± 0.142 × 10(-5)) was lower than control group (55.6 × 10(-5) ± 51.05 × 10(-5)) in new-born (t = 102.225, P < 0.05); the expression of Nkx2.1 mRNA in non-treatment hypothyroidism group (8.09 × 10(-5) ± 8.21 × 10(-5)) was lower than control group (13.9 × 10(-5) ± 7.43 × 10(-5)) in 20th day after birth (t = 9.235, P < 0.05). The trend of Nkx2.1 mRNA in hypothyroidism groups was decreased in group supplied with L-T(4) in medium dosage in early stage descends in 17th day of pregnancy, new-born and 20th day after birth (57.1 × 10(-5) ± 22.90 × 10(-5)), (30.8 × 10(-5) ± 27.20 × 10(-5)), (17.1 × 10(-5) ± 0.623 × 10(-5)) (F = 13.394, P < 0.01). The expression of Nkx2.1 mRNA in hypothyroidism groups supplied with L-T(4) in medium dosage in early stage in 17th day of pregnancy, new-born and 20th day after childbirth was closest to the control group in every period (t values were 0.225, 0.336, 0.345, all P values > 0.05).

CONCLUSIONThe difference in the expression of homeobox gene Nkx2.1 mRNA is highly related to the level of thyroid hormone.

Animals ; Animals, Newborn ; genetics ; metabolism ; Brain ; metabolism ; Female ; Hypothyroidism ; drug therapy ; Nuclear Proteins ; genetics ; Pregnancy ; Pregnancy, Animal ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Thyroid Nuclear Factor 1 ; Thyroxine ; pharmacology ; Transcription Factors ; genetics

OBJECTIVETo study the effects of excess iodine intake on neurogranin expression in cerebrum of filial mice and the intervention of selenium.

METHODSSixty BALB/c mice were divided randomly into four groups with different drinking water: control group (tap water, NC), excess iodine group (3000 microg/L I, EL +), supplementing selenium group (200 microg/L Se, Se +) and the excess iodine plus selenium (3000 microg/L + I 200 microg/L Se, EI + Se +) group. The mice were mated at the end of the fourth month. Serum T4 and T3 were determined on postnatal day 14 and 28. The expression level of neurogranin in filial cerebrum was measured by immunohistochemistry and Western blot.

RESULTSSerum T4 level in EI (68.78 +/- 11.10 nmol/ L) + was lower significantly than that in NC (100.85 +/- 11.47 nmol/ L) and EI + Se + (93.15 +/- 12.10 nmol/ L) on postnatal day 14. Western blot analysis showed that the relative level of neurogranin in EI + (0.621 +/- 0.041) was lower than that in NC (0.841 +/- 0.039) and EI + Se + (0.781 +/- 0.029) on postnatal day 14 (P < 0.05). No significant difference in serum T4 and neurogranin level between four groups on postnatal day 28.

CONCLUSIONExcess iodine intake might change the expression of neurogranin in filial cerebrum and the selenium supplementation might alleviate it.

Animals ; Female ; Iodine ; adverse effects ; Male ; Mice ; Mice, Inbred BALB C ; Neurogranin ; biosynthesis ; Selenium ; pharmacology ; Telencephalon ; metabolism ; Thyroxine ; blood ; Triiodothyronine ; blood

OBJECTIVEAlthough several reports documented the association of congenital hypothyroidism (CH) and left ventricular (LV) function in infants or neonates, right ventricular (RV) function in neonates with CH has not been previously studied. The aim of the present study was to assess RV function in neonates with CH before and after thyroxine substitution therapy by quantitative tissue velocity imaging (QTVI) and tissue tracking imaging (TTI).

METHODSFifty-two neonates aged 18-28 days (25 males and 27 females) with CH and 35 healthy neonates aged 18-28 days (16 males and 19 females) were studied by QTVI, TTI as well as conventional pulsed-wave Doppler echocardiography (PWD). The standard apical four-chamber view for long-axis motion of the right ventricle was used for echocardiographic evaluation. Peak systolic displacement (D), peak systolic velocity (Vs), peak early (Ve) and late (Va) diastolic velocity of tricuspid annule were measured, Ve/Va ratio was calculated as well. Transtricuspid flow velocity during early diastole (E) and late diastole (A) were also measured by pulsed-wave Doppler echocardiography. PWD and E/A ratio were calculated too. For each neonate, serum hormone levels of TSH, TT(3), TT(4), FT(3) and FT(4) were measured with a standard chemiluminescent immunoassay. After 1 month of levothyroxine (L-T(4)) substitution therapy in CH neonates, all the echocardiographic evaluations and biochemical tests were re-evaluated. Correlation analysis was also made between serum thyroid hormones levels and right ventricular function.

RESULTSThe indices of right ventricular diastolic function by PWD (E and E/A ratio) in CH group were (45 +/- 10) cm/s and (0.8 +/- 0.3), respectively. Compared with controls, E and E/A ratio in CH neonates were significantly lower (P < 0.001, respectively), while A did not differ between the two groups (P > 0.05). QTVI and TTI showed that right diastolic function (Ve and Ve/Va ratio) as well as right systolic function (Vs and D) in CH group were (3.69 +/- 1.38) cm/s, (0.74 +/- 0.19) cm/s, (4.38 +/- 0.63) cm/s and (0.52 +/- 0.12) cm, respectively. CH neonates had significantly lower Ve, Ve/Va ratio, Vs and D of tricuspid annular velocity (P < 0.001, respectively), whereas there was no significant difference in Va between the two groups (P > 0.05). After 1 month of substitutive therapy, CH neonates showed a significant increase of Ve, Ve/Va ratio, Vs, D, E, and E/A ratio, (6.92 +/- 1.86) cm/s, (1.13 +/- 0.22), (5.92 +/- 1.03) cm/s, (0.78 +/- 0.17) cm, (61 +/- 10) cm/s and (1.1 +/- 0.4), respectively (P < 0.001). Those parameters were positively correlated with serum TT(3), TT(4), FT(3) and FT(4) levels (P < 0.01, respectively), and were negatively correlated with serum TSH levels (P < 0.01, respectively).

CONCLUSIONSOur findings suggest that neonates with CH are associated with right ventricular subclinical systolic and diastolic dysfunction, which can be reversed by early L-T(4) substitution therapy. QTVI and TTI are valuable methods to evaluate right ventricular function in neonates. Systolic and diastolic velocities of the tricuspid annulus measured by QTVI and TTI are useful and accurate to assess RV function in neonates.

Adult ; Blood Flow Velocity ; Child, Preschool ; Congenital Hypothyroidism ; physiopathology ; Diastole ; drug effects ; physiology ; Echocardiography ; Echocardiography, Doppler, Pulsed ; Female ; Heart Ventricles ; drug effects ; physiopathology ; Humans ; Male ; Systole ; drug effects ; physiology ; Thyrotropin ; pharmacology ; Thyroxine ; blood ; pharmacology ; Tricuspid Valve ; physiopathology ; Ventricular Function, Left ; drug effects ; physiology ; radiation effects ; Ventricular Function, Right ; drug effects ; physiology

OBJECTIVETo investigate the effect of selenium supplementation on the selenium status and selenoenzyme, especially the activity and mRNA expression of type 1 deiodinase (D1) in mice with excessive iodine (EI) intake and to explore the mechanism of selenium intervention on iodine-induced abnormities.

METHODSWeanling female BALB/c mice were given tap water or 3 mg/L of iodine or supplemented with 0.5 mg/L or 1.0 mg/L of selenium in the presence of excessive iodine for 5 months. Selenium status, thyroid hormone level, hepatic and renal D1 activity and mRNA expression were examined.

RESULTSExcessive iodine intake significantly decreased the selenium concentration in urine and liver, and the activity of glutathione peroxidase (GSH-Px) in liver. Meanwhile, serum total T4 (TT4) increased while serum total T3 (TT3) decreased. Hepatic D1 enzyme activity and mRNA expression were reduced by 33% and 86%, respectively. Renal D1 enzyme activity and mRNA were reduced by 30% and 55%, respectively. Selenium supplementation obviously increased selenium concentration, activity of GSH-Px and Dl as well as mRNA expression of D1. However, increasing the supplementation of Se from 0.5 to 1.0 mg/L did not further increase selenoenzyme activity and expression.

CONCLUSIONRelative selenium deficiency caused by excessive iodine plays an essential role in the mechanism of iodine-induced abnormalities. An appropriate dose of selenium supplementation exercises a beneficial intervention.

Animals ; Antioxidants ; pharmacology ; Creatinine ; metabolism ; urine ; Dietary Supplements ; Female ; Iodide Peroxidase ; genetics ; metabolism ; Iodine ; toxicity ; urine ; Kidney ; metabolism ; Liver ; metabolism ; Mice ; Mice, Inbred BALB C ; RNA, Messenger ; metabolism ; Selenium ; pharmacology ; urine ; Thyroxine ; blood ; Triiodothyronine ; blood

AIMTo know the effect of cysteamine (CS) on the plasma levels of somatostatin (SS) and some metabolic hormones in adult geese.

METHODSFourteen adult crossbred geese (Chuan white x Tai lake) fitted with chronic wing vein cannulas were used in this study to evaluate the effect of CS on SS, TSH, T3 and T4 levels. The experiment was consisted of control and treated phase. The diet was added CS at dosage of 100 mg/kg bw on the first day of the treated phase. The blood samples were collected from the cannulas and analyzed by radioimmunoassay.

RESULTSThe plasma SS concentration was (1.87 +/- 0.10) microg/L in control phase. Whereas SS concentrations on day 1, 3, 5, 7 of treated phase were decreased markedly (P < 0.05 or P < 0.01). Thereafter it was rose on the seventh day, however it was still lower than that of control. The thyroid stimulating hormone (TSH) content (2.45 +/- 0.31 mIU/L) was significantly decreased by 21.63% (P < 0.01) on day 1, and 18.37% (P > 0.05) on day 3 and day 5. Comparing with control phase (5.41 +/- 0.98 microg/L), T4 contents were elevated by 60.26% (P < 0.01), 43.25% (P < 0.01), 37.15% (P < 0.01) and 16. 82% (P < 0.01) respectively on day 1, 3, 5, 7. T3 level was (1.05 +/- 0.06) microg/L in control phase, whereas the levels was significantly increased by 36.19% (P < 0.01) on day 3. Also, the insulin concentration was higher than that of control (4.43 +/- 0.41 mU/ L) by 18.28% (P < 0.05) on the day 5.

CONCLUSIONThese results indicate that CS can decrease the plasma SS and TSH levels, whereas increase the levels of T4, T3 and insulin, therefore change metabolism, improve the nutrition transform and accelerate the growth in geese.

Animals ; Cysteamine ; pharmacology ; Diet ; Geese ; Insulin ; blood ; Somatostatin ; blood ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood

OBJECTIVETo explore the effects of thyroid hormone (TH) on cardiac function and peripheral lymphocyte beta-adrenoceptors (beta-ARs) of patients with chronic congestive heart failure (CHF).

METHODSTwenty-eight patients with class III or IV advanced CHF due to dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM) were randomly divided into groups A and B. L-thyroxine (L-T(50)) was administered to group B. Exercise tolerance, chest X-rays, and echocardiographic parameters were obtained before and after one month of treatment, Ficoll-hypaque solution was used to separate peripheral lymphocytes, and (125)I-pindolol radioligand binding was used to measure beta-AR levels in peripheral lymphocytes.

RESULTSL-T(50) therapy improved cardiac output [CO, (2.98 +/- 0.31)L/min vs (3.24 +/- 0.28) L/min, P < 0.01], left ventricular ejection fraction (LVEF, 26.21% +/- 3.21% vs 37.93% +/- 9.01%, P < 0.01), and decreased isovolumetric relaxation time (IVRT, 0.12 +/- 0.04 vs 0.10 +/- 0.02, P < 0.01). Serum TH levels and the maximal number of beta-AR binding sites (beta(max)) in peripheral lymphocytes were lower in patients with CHF than in normal healthy people, but L-T(50) administration induced a beta-AR up-regulation on peripheral lymphocyte surfaces. L-T(50) was well tolerated without episodes of ischemia or arrhythmia. There was no significant change in heart rate or metabolic rate.

CONCLUSIONTH administration improves cardiac function and beta-AR expression in peripheral lymphocytes of patients with CHF.

Adult ; Aged ; Blood Pressure ; drug effects ; Chronic Disease ; Echocardiography ; Female ; Heart ; drug effects ; physiology ; Heart Failure ; physiopathology ; Heart Rate ; drug effects ; Humans ; Lymphocytes ; chemistry ; Male ; Middle Aged ; Receptors, Adrenergic, beta ; analysis ; Thyroxine ; pharmacology

AIMTo determine whether 7-oxo-dehydroepiandrosterone (7-oxo-DHEA) can reverse the hypoimmunity in BALB/c mice exposed to chronic mild stress.

METHODSA chronic mild stress animal model was established by subjecting BALB/c mice to a stressful regimen arranged in an unpredicted manner for 4 consecutive weeks. Immunological function alternations under chronic mild stress were assessed by lymphocytes proliferative response to mitogens and NK cell lysis activity test.

RESULTSThe studies showed the correlation between the state of depression and abnormalities in the immune response, such as a decrease of T lymphocytes proliferative response to Con A and suppression of cytotoxic of NK cell. Meanwhile, significant decrease of T3 and T4 levels was also observed. When stressed mice were daily given 7-oxo-DHEA 15 mg.kg-1, lymphocyte proliferative response and the NK cell activity were significantly enhanced and the decreased levels of T3 and T4 were restored in the stressed mice.

CONCLUSION7-oxo-DHEA can improve the depressive symptoms and hypoimmunity of BALB/c mice induced by chronic mild stress as its parent DHEA.

Adjuvants, Immunologic ; pharmacology ; Animals ; Antidepressive Agents ; pharmacology ; Cell Division ; drug effects ; Chronic Disease ; Dehydroepiandrosterone ; analogs & derivatives ; pharmacology ; Killer Cells, Natural ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Stress, Physiological ; blood ; immunology ; T-Lymphocytes ; immunology ; pathology ; Thyroxine ; blood ; Triiodothyronine ; blood