OBJECTIVE: To explore the mechanism of Radix Scrophulariae (RS) extracts in the treatment of hyperthyroidism rats by regulating proliferation, apoptosis, and autophagy of thyroid cell through the mammalian sterile 20-like kinase 1 (MST1)/Hippo pathway. METHODS: Twenty-four rats were randomly divided into 4 groups according to a random number table: control, model group, RS, and RS+Hippo inhibitor (XMU-MP-1) groups (n=6 per group). Rats were gavaged with levothyroxine sodium tablet suspension (LST, 8 μ g/kg) for 21 days except for the control group. Afterwards, rats in the RS group were gavaged with RS extracts at the dose of 1,350 mg/kg, and rats in the RS+XMU-MP-1 group were gavaged with 1,350 mg/kg RS extracts and 1 mg/kg XMU-MP-1. After 15 days of administration, thyroid gland was taken for gross observation, and histopathological changes were observed by hematoxylin-eosin staining. The structure of Golgi secretory vesicles in thyroid tissues was observed by transmission electron microscopy. The expression of thyrotropin receptor (TSH-R) was observed by immunohistochemistry. Terminal-deoxynucleoitidyl transferase mediated nick end labeling assay was used to detect cell apoptosis in thyroid tissues. Real-time quantity primer chain reaction and Western blot were used to detect the expressions of MST1, p-large tumor suppressor gene 1 (LATS1), p-Yes1 associated transcriptional regulator (YAP), proliferating cell nuclear antigen (PCNA), G₁/S-specific cyclin-D1 (Cyclin D1), B-cell lymphoma-2 (Bcl-2), Caspase-3, microtubule-associated proeins light chain 3 II/I (LC3-II/I), and recombinant human autophagy related 5 (ATG5). Thyroxine (T4) level was detected by enzyme-linked immunosorbent assay. RESULTS: The thyroid volume of rats in the model group was significantly increased compared to the normal control group (P<0.01), and pathological changes such as uneven size of follicular epithelial cells, disorderly arrangement, and irregular morphology occurred. The secretion of small vesicles by Golgi apparatus was reduced, and the expressions of receptor protein TSH-R and T4 were significantly increased (P<0.01), while the expressions of MST1, p-LATS1, p-YAP, Caspase-3, LC3-II/I, and ATG5 were significantly decreased (P<0.01). The expressions of Bcl-2, PCNA, and cyclin D1 were significantly increased (P<0.01). Compared with the model group, RS extracts reduced the volume of thyroid gland, improved pathological condition of the thyroid gland, promoted secretion of the secretory vesicles with double-layer membrane structure in thyroid Golgi, significantly inhibited the expression of TSH-R and T4 levels (P<0.01), upregulated MST1, p-LATS1, p-YAP, Caspase-3, LC3-II/I, and ATG5 expressions (P<0.01), and downregulated Bcl-2, PCNA, and Cyclin D1 expressions (P<0.01). XMU-MP-1 inhibited the intervention effects of RS extracts (P<0.01). CONCLUSION RS extracts could inhibit proliferation and promote apoptosis and autophagy in thyroid tissues through MST1/Hippo pathway for treating hyperthyroidism.
Rats ; Humans ; Animals ; Hippo Signaling Pathway ; Proliferating Cell Nuclear Antigen/metabolism* ; Cyclin D1/pharmacology* ; Caspase 3/metabolism* ; Protein Serine-Threonine Kinases/pharmacology* ; Apoptosis ; Hyperthyroidism/drug therapy* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Thyrotropin/pharmacology* ; Mammals/metabolism*

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

OBJECTIVETo study and evaluate the curative effect and mechanism of Qiangxin Granule (QXG) in intervening chronic heart failure (CHF) rats with Xin-qi deficiency complicated blood stasis and edema syndrome (XQD-BS-ES).

METHODSTotally 72 SD rats of clean grade were randomly divided to the normal control group (n =10) and the model group (n = 62). The XQD-BS-ES rat model was established by adriamycin plus propylthiouracil method. Survived modeled rats were then randomly divided to 5 groups i.e., the model group (n = 11, administered with normal saline by gastrogavage), the Western medicine (WM) group (n =11 , administered with perindopril and hydrochlorothiazide by gastrogavage), the low dose QXG (QXG(L)) group (n = 11, administered with 9.26 g/kg QXG by gastrogavage), the middle dose QXG (QXG(M)) group (n = 11, administered with 18.52 g/kg QXG by gastrogavage), the high dose QXG (QXG(H)) group (n = 11, administered with 37.04 g/kg QXG by gastrogavage). After 4 weeks of treatment, left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), brain natriuretic peptide (BNP), heart rate (HR), respiratory rate (RR), urine output, ear temperature, exhaustive swimming test (EST), tri-iodothyronine (T3), tetra-iodothyronine (T4), thyroid stimulating hormone (TSH), as well as heart, lung, liver weight index and their pathological sections, and high sensitivity C-reactive protein (HS-CRP), angiotensin II (Ang II), carbohydrate antigen 125 (CA125) were detected and compared.

RESULTSCompared with the normal control group, LVEF, LVFS, BNP, HR, RR, urine output, ear temperature, EST, T3, T4, TSH, HS-CRP, Ang II, and CA125 changed significantly in the model group (P < 0.01). Compared with the model group after treatment, LVEF, LVFS, BNP, urine output, EST, T4, heart and liver weight index, HS-CRP, Ang II, CA125 were significantly improved in each QXG group (P < 0.05, P < 0.01). Moreover, TSH was improved in the QXGL and QXG(M) groups (P < 0.05); ear temperature and T3 in the QXG(M) were also improved (P < 0.05); the lung weight index decreased in the QXG(M) and QXG(H) groups (P < 0.01). Compared with the WM group, T4 and CA125 were obviously improved in all QXG groups (P < 0.01); BNP and ear temperature were obviously improved in QXG(L) and QXG(M) groups (P < 0.05, P < 0.01); LVEF, LVFS and TSH were obviously improved in the QXG(M) group (P < 0.05, P < 0.01). And as far as each treatment group, LVEF, LVFS, urine output increased significantly after treatment (P < 0.01); EST obviously increased in QXG(M) and QXG(H) groups (P < 0.01); ear temperature increased in all QXG groups (P < 0.05, P < 0.01). Moreover, compared with the model group, pathological changes of heart, lung, and liver were improved to some degree in each treatment group, especially in the QXG(M) group.

CONCLUSIONSGood curative effect was shown in each QXG group. QXG could improve LVEF, LVFS and BNP of CHF rats of XQD-BS-ES, as well as T3, T4, TSH, EST, urine output, and ear temperature. Moreover, QXG showed superiority than WM group in this respect.

Angiotensin II ; Animals ; C-Reactive Protein ; Chronic Disease ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Edema ; Heart ; Heart Failure ; drug therapy ; Heart Ventricles ; Medicine, Chinese Traditional ; Natriuretic Peptide, Brain ; Qi ; Rats ; Rats, Sprague-Dawley ; Syndrome ; Thyrotropin ; Ventricular Function, Left

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

Ginseng and its effective components are famous for their influence to enhance human immunity, regulate endocrine and antioxidant action. However, the different effects of different components are not clear. In this study, Wistar rats were used to study the effects of main components of ginseng, including total ginsenoside, panaxadiol saponins, panaxtrol saponin and ginseng polysaccharide. The results showed that the effects of panaxadiol saponins and ginseng polysaccharide on improving animal immune organ weight, plasma interleukin 2 (IL-2), interleukin 6 (IL-6), plasma gamma-interferon (IFN-γ), tumor necrosis factor alpha (TNF-α) were better than that of the other groups. Total ginsenoside and panaxtrol saponin can effectively increase the concentration of spleen NK cells (NKC) while panaxadiol saponins and ginseng polysaccharide can significantly increase the concentrations of rat plasma adrenocorticotrophic hormone (ACTH), corticosterone (CORT) and thyroid stimulating hormone (TSH). As for the effect of increasing organization nitric oxide (NO) and superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA), total ginsenoside is better than that of other groups. In brief, different components in ginseng possess different effects on enhancing immunity, regulating endocrine and resisting oxidation. Panaxadiol saponins and ginseng polysaccharide are better in enhancing immune, and total ginsenoside shows advantages in resisting oxidation and stress.
Adrenal Glands ; drug effects ; growth & development ; Adrenocorticotropic Hormone ; blood ; Animals ; Brain ; drug effects ; metabolism ; Corticosterone ; blood ; Ginsenosides ; pharmacology ; Glutathione ; metabolism ; Immune System ; drug effects ; physiology ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; Interleukin-6 ; blood ; Killer Cells, Natural ; drug effects ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Organ Size ; drug effects ; Panax ; chemistry ; Polysaccharides ; pharmacology ; Random Allocation ; Rats, Wistar ; Saponins ; pharmacology ; Spleen ; drug effects ; growth & development ; Superoxide Dismutase ; metabolism ; Thymus Gland ; drug effects ; growth & development ; Thyrotropin ; 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

AIMTo investigate the effect of hypothalamic thyrotropin-releasing hormone (TRH) on cardiac function and its mechanism.

METHODSThe Sprague-Dawley rats were mounted in a stereotaxic apparatus and a guide cannula placed in the left hypophysiotropic area, through which TRH were microinjected in presence or absence of L-NAME and atropine. The left ventricular systolic pressure (LVSP), heart rate (HR) and the maximum velocity of ascending or descending in intraventricular pressure (+/- dp/dt(max)) were recorded.

RESULTS(1) TRH microinjected into the hypophysiotropic area induced a significant increase of LVSP, HR, dp/dt and-dp/dt(max) (P < 0.05, P < 0.01). (2) L-NAME significant increased LVSP and pretreatment with L-NAME inhibited the positive effects induced by TRH. (3) Atropine increased LVSP and dp/dt(max) (P < 0.05), but it significantly descended heart rate (P < 0.05). Pretreatment with atropine weakened the tachycardiac response induced by TRH.

CONCLUSION(1) Hypothalamic TRH can produce positive inotropic and chronotropic response to myocardium. (2) Hypothalamic endogenous NO can descend LVSP, but has no effects on HR, dp/dt(max), and-dp/dt(max). The effect of TRH is through nitric oxide-dependent pathway. (3) Hypothalamic endogenous cholinergic transmitter can produce negative chronotropic and positive inotropic response to myocardium. Hypothalamic TRH mediates cardiac function maybe partly through cholinergic M receptor.

Animals ; Blood Pressure ; Heart Rate ; Heart Ventricles ; drug effects ; Hypothalamus ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley ; Thyrotropin-Releasing Hormone ; administration & dosage ; pharmacology ; Ventricular Function, Left ; drug effects

TSH secretion is controlled by the stimulatory action of hypothalamic TRH and the inhibition via central dopaminergic and somatostatinergic mechanisms as well as by a hypothalamic inhibitory action of thyroid hormones. Metoclopramide is DA2 receptor blockade which can accelerate to elevate the concentration of serum TSH in hypothyroidism, which is accompanied by a progressive loss of dopaminergic tone as demonstrated by a progressive increase in prolaction serum levels, especially in patients with differentiated thyroid carcinoma(DTC). So the period of L-thyroxine withdrawal is contracted and the symptoms of hypothyroidism is released. It's important to monitor and treat DTC patients with radioactive iodide.
Dopamine Antagonists ; pharmacology ; Humans ; Hyperthyroidism ; blood ; drug therapy ; Hypothalamo-Hypophyseal System ; drug effects ; physiology ; Hypothyroidism ; blood ; drug therapy ; Metoclopramide ; chemistry ; pharmacology ; Thyroid Gland ; drug effects ; physiology ; Thyroid Hormones ; blood ; Thyrotropin ; 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

Both fertilization promoting peptide and adenosine stimulate capacitation but inhibit spontaneous acrosome loss by modulation of the adenylyl cyclase (AC)/cAMP signal transduction pathway. This is a review aimed at analyzing the function of fertilization promoting peptide during this process. The possible molecular basis is also discussed.
Acrosome ; drug effects ; Adenylyl Cyclases ; metabolism ; Animals ; Cyclic AMP ; metabolism ; Humans ; Male ; Pyrrolidonecarboxylic Acid ; analogs & derivatives ; Signal Transduction ; drug effects ; Spermatozoa ; drug effects ; physiology ; Thyrotropin-Releasing Hormone ; analogs & derivatives ; pharmacology