Effects of arsenic exposure on E2 and TRH and their receptor mRNA expressions in rats / 环境与职业医学

Background Arsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear. Objective To investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism. Methods Seventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups [0.8, 4.0, and 20.0 mg·kg−1 sodium arsenite (NaAsO2)]; estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO2 by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg−1 ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR). Results (1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P<0.05), and the serum E2 level of male rats was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), and the change of female E2 was greater than that of male rats. Compared with the control group, the relative expression levels of ERα mRNA and ERβ mRNA in female rats were increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), so were the relative expression levels of ERα mRNA in male rats (P<0.05). (2) TRH and its receptor mRNA: Compared with the control group, the serum TRH level of female rats was increased in the high-dose arsenic group (P<0.05), the relative expression level of TRHR mRNA was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05). Results (1) and results (2) suggested that females were more likely than males to have abnormal changes in E2, TRH, and related receptor genes after arsenic exposure. (3) Compared with female rats in the medium-high dose arsenic exposure group, the expressions of TRH and TRHR induced by arsenic exposure were inhibited after the intervention of ICI182780 (P<0.05), suggesting that arsenic in the hypothalamus may have toxic effects on TRH and TRHR by inducing estrogen-like effects. Conclusion Arsenic exposure can induce estrogen-like effects in the hypothalamus, interfere with thyroid function, and show dose-dependent and sex differences. E2 and TRH and their receptors may be the toxic pathway of arsenic-related estrogen-like effect.

TRH stimulation test in patients with repeatedly elevated TSH and normal FT4 / Teste de estímulo com TRH em pacientes com TSH repetidamente elevado e T4L normal

ABSTRACT Subclinical hypothyroidism (SCH) is defined by elevated thyroid-stimulating hormone (TSH) with normal free thyroxine (FT4). We aimed to evaluate the thyrotropin-releasing hormone (TRH) stimulation test in patients with repeatedly elevated TSH (up to 10 mIU/l) and normal FT4, but without apparent thyroid disease. Women with TSH > 4.5 and ≤ 10 mIU/l (in two measurements) and normal FT4 were selected. Women with a known non-thyroid cause of TSH elevation, those treated with anti-thyroid drugs, amiodarone, lithium, and those with a history of thyroidectomy, neck radiotherapy and 131I treatment were excluded. Seventy women had negative antithyroperoxidase antibodies. Ultrasonography revealed a eutopic thyroid, usual echogenicity, and a volume ≤ 15 ml, and they underwent the TRH stimulation test during initial evaluation. After stimulation with TRH, TSH > 30 mIU/l was observed in 38 women (expected response), while 32 women had TSH < 20 mIU/l (inadequate response). Age, basal TSH or thyroid volume did not differ between both groups, but FT4 concentrations were significantly lower in the first group. Follow-up was available for 66/70 women. Seven women developed a need for levothyroxine, all of them in the group with an adequate response to TRH [7/36 (19.4%) versus 0/30]. The results suggest that some cases of TSH elevation (even persistent) do not represent the early stage of thyroid insufficiency.

RESUMEN El hipotiroidismo subclínico (HSC) es definido por la elevación de los niveles de hormona tiroestimulante (TSH) con los niveles de tiroxina libre (T4L) dentro de rangos de normalidad. El objetivo de este reporte fue evaluar la prueba de estímulo con hormona liberadora de tirotropina (TRH) en pacientes con TSH persistentemente elevado (hasta 10 mUI/l) y T4L normal, pero sin enfermedad tiroidea aparente. Se eligieron mujeres con TSH > 4,5 y ≤ 10 mUI/l (en dos medidas) y T4L normal. Se excluyeron aquellas con causa no tiroidea conocida de alza de TSH además de las tratadas con medicamentos antitiroideos, amiodarona, litio y con historia de tiroidectomía, radioterapia cervical y tratamiento con 131I. Setenta mujeres presentaron anticuerpos antitiroperoxidasa negativos. La ecografía mostró tiroides eutópica, ecogenicidad usual y volumen ≤ 15 ml; todas se sometieron a la prueba de estímulo con TRH en la evaluación inicial. Tras estímulo con TRH, TSH > 30 mUI/l se observó en 38 mujeres (respuesta esperada), mientras 32 mujeres presentaron TSH < 20 mUI/l (respuesta inadecuada). El seguimiento estuvo disponible para 66/70 mujeres. Siete pacientes evolucionaron con necesidad de levotiroxina, todas ellas en el grupo con respuesta adecuada al TRH [7/36 (19,4%) versus 0/30]. Los resultados sugieren que algunos casos de alza de TSH (aunque persistente) no representan la fase inicial de una insuficiencia tiroidea.

RESUMO O hipotireoidismo subclínico (HSC) é definido pela elevação dos níveis de hormônio tireoestimulante (TSH) com os níveis de tiroxina livre dentro da normalidade (T4L). O objetivo deste relato foi avaliar o teste de estímulo com hormônio liberador de tirotrofina (TRH) em pacientes com TSH repetidamente elevado (até 10 mUI/l) e T4L normal, mas sem doença tireoidiana aparente. Mulheres com TSH > 4,5 e ≤ 10 mUI/l (em duas medidas) e T4L normal foram selecionadas. Foram excluídas aquelas com causa não tireoidiana conhecida de elevação do TSH, além das tratadas com medicamentos antitireoidianos, amiodarona, lítio e com histórico de tireoidectomia, radioterapia cervical e tratamento com 131I. Setenta mulheres apresentaram anticorpos antitireoperoxidase negativos. A ultrassonografia revelou tireoide eutópica, ecogenicidade usual e volume ≤ 15 ml; todas foram submetidas ao teste de estímulo com TRH na avaliação inicial. Após estímulo com TRH, TSH > 30 mUI/l foi observado em 38 mulheres (resposta esperada), enquanto 32 mulheres apresentaram TSH < 20 mUI/l (resposta inadequada). Idade, TSH basal ou volume da tireoide não diferiram entre os dois grupos, mas as concentrações de T4L foram significativamente menores no primeiro grupo. O acompanhamento foi disponível para 66/70 mulheres. Sete pacientes evoluíram com necessidade de levotiroxina, todas elas no grupo com resposta adequada ao TRH [7/36 (19,4%) versus 0/30]. Os resultados sugerem que alguns casos de elevação do TSH (mesmo persistente) não representam a fase inicial de uma insuficiência tireoidiana.

Effect of Carbamazepine on the Serum Level of Thyrotropin-Releasing Hormone

Background: The thyroid gland is endocrine gland located in front and lower side of neck. Thyroid gland secretes two types of thyroid hormones that are triiodothyronine (T3) and tetraiodothyronine (T4). The hypothalamus is a center for regulation of thyroid hormones. It senses the low hormone levels and in turn releases thyrotropin-releasing hormone (TRH). TRH stimulates anterior pituitary to release TSH which then acts on the thyroid gland to maintain normal level of T3 and T4. The objective of study is to determine the effects of carbamazepine on TRH in euthyroid rabbits.Methods: An experimental study performed on 30 rabbits. These were divided into three groups having 10 rabbits in each group. 10 rabbits were treated with 10mg/kg/day of CBZ (OD), other 10 with 35mg/kg/day CBZ (three divided doses) and 10 rabbits served as control. T3, FT4, TSH and TRH levels were evaluated at baseline and after 21 days of treatment in all three groups by Electro-chemiluminescence immunoassay and ELISA respectively.Results: Comparison of the hormone levels of the control group and the group having a dose of 10 mg/kg/day for 21 day of treatment. Comparative results showed serum level of T3 (P=0.031), FT4 (P=0.030), and TRH (P=0.044) levels significantly lower than the control group and TSH (P=0.057) levels remain unaltered. It was also found that group having a dose of 35 mg/kg/day; TDS showed decrease in T3 (P value 0.001), FT4 (P=0.001), TSH (P=0.003) and TRH (P=0.001) level as compared to control group.Conclusions: Our data suggest that Carbamazepine monotherapy does alter thyroid hormones and its central regulatory hormone TRH. Decrease in TRH level increase level of depression and suicidal thoughts and also risk of tertiary hypothyroidism. These findings could have very important clinical implications.

Effect of Chronic Iodine Excess on Type Ⅱ Deiodinase in Hypothalamus and Serum Thyrotropin Releasing Hormone Level in Rats / 中国医科大学学报

Objective To investigate the effect of chronic iodine excess on hypothalamic type Ⅱ deiodinase (D2) and serum thyrotropin releasing hormone (TRH) levels in rats. Methods One hundred and eighty four-week-old Wistar rats were randomly divided into control group (NI) and 3-fold, 6-fold, 10-fold, and 50-fold high iodine (HI) groups. Double distilled water and iodine solutions at concentrations of 277, 692, 1 245, and 6 788 μg/L were administered for 4, 8, 12, and 24 weeks, respectively. Brain tissue was taken after sacrifice, serum TRH levels were detected by ELISA, and hypothalamic D2 levels were detected by immunohistochemistry. Results Serum TRH levels in the 10-fold and 50-fold HI groups at 4 weeks, 6-fold and 50-fold HI groups at 8 weeks, 6-fold HI group at 12 weeks, and the 3-fold and 50-fold HI groups at 24 weeks were significantly lower than those in the control group (P ＜ 0.05). The results of immunohistochemistry revealed that the expression of hypothalamic D2 at each time-point was increased in the HI groups in comparison with the control group. Conclusion Chronic iodine excess can boost the expression of hypothalamic D2 and lessen the serum TRH level in rats.

Influence of 131 I therapy on thyroid function and bone metabolism in patients with Graves disease / 中国基层医药

Objective To analyze the influence of 131 I therapy on thyroid function and bone metabolism in patients with Graves 's disease. Methods From February 2014 to January 2017,60 Graves patients in Shaoxing Central Hospital were studied. According to the random number table method,they were divided into observation group and control group,with 30cases in each group. The patients in the control group were treated with methimidazole,and the patients in the observation group were treated with 131 I combined with methimidazole. After treatment for 1 month, the clinical efficacy,three triiodothyronine (FT3 ),free thyroxine (FT4 ),thyroid stimulating hormone (TSH) concen-tration,parathyroid hormone (PTH),procollagen amino terminal propeptide (PINP) and osteocalcin (OCN),1,25 hydroxyvitamin D3(1,25(OH)2D3),bone mineral density (BMD),the incidence of goiter,exophthalmos,incidence of hypothyroidism of the two groups were observed. Results After treatment,the total effective rate of the observation group was 93. 33％ ,which of the control group was 73. 33％ . There was statistically significant difference between the two groups (χ2 = 4. 320,P = 0. 037). Before treatment,the levels of FT3 ,FT4 ,TSH between the two groups had no statisticallysignificant differences (all P > 0. 05). After treatment,the FT3 ,FT4 levels of the observation group were (12. 41 ± 1. 24) pmol/ L,(18. 33 ± 4. 25) pmol/ L,respectively,which were significantly lower than those of the control group[ (15. 98 ± 1. 30)pmol/ L,(22. 75 ± 4. 31)pmol/ L](t = 10. 884,P < 0. 0001;t = 4. 000,P < 0. 000). The concentration of TSH in the observation group was (2. 16 ± 0. 39)mIU/ L,which was significantly higher than that of the control group[(1. 72 ± 0. 34)mIU/ L](t = 4. 658,P < 0. 0001). Before treatment,the PTH,PINP,OCN,1,25 (OH)2D3 and BMD between the two groups had no statistically significant differences (all P > 0. 05). After treat-ment,the PINP and OCN of the observation group were (43. 21 ± 3. 69) μg/ L,(27. 42 ± 6. 48) μg/ Lrespectively, which were significantly lower than those of the control group [(55. 87 ± 3. 71) μg/ L,(31. 84 ± 6. 55) μg/ L] (t =13. 252,P < 0. 0001;t = 2. 628,P = 0. 011). The PTH,1,25 ( OH)2D3 and BMD of the observation group were (55. 87 ± 3. 18)ng/ L,(25. 16 ± 2. 84) nmol/ L,(0. 98 ± 0. 17) g/ cm2 ,respectively,which were significantly higher than those in the control group [(49. 89 ± 3. 21)ng/ L,(23. 2 ± 2. 76)nmol/ L,(0. 85 ± 0. 15)g/ cm2 ] (t = 7. 249, P < 0. 001;t = 2. 697,P = 0. 009;t = 3. 141,P = 0. 003). After treatment,the incidence rate of exophthalmos in the observation group was 6. 67％ ,which in the control group was 30. 00％ ,there was statistically significant difference between the two groups (χ2 = 5. 455,P = 0. 020). The incidence rate of goiter of observation group was 3. 33％ ,which was significantly lower than 23. 33％ of the control group (χ2 = 5. 192,P = 0. 023). The incidence rate of hypothy-roidism of the observation group was 13. 33％ ,which in the control group was 10. 00％ ,the difference between the two groups was not statistically significant (χ2 = 0. 162,P = 0. 688). Conclusion 131 I therapy has good clinical effect on Graves disease. It can effectively improve the thyroid function and bone metabolism and has high safety. It is worthy of widely application and popularizing in clinic.

Subclinical hypothyroidism diagnosed by thyrotropin-releasing hormone stimulation test in infertile women with basal thyroid-stimulating hormone levels of 2.5 to 5.0 mIU/L

OBJECTIVE: To investigate the prevalence of subclinical hypothyroidism (SH) diagnosed by thyrotropin-releasing hormone (TRH) stimulating test in infertile women with basal thyroid-stimulating hormone (TSH) levels of 2.5 to 5.0 mIU/L. METHODS: This study was performed in 39 infertile women with ovulatory disorders (group 1) and 27 infertile women with male infertility only (group 2, controls) who had basal serum TSH levels of 2.5 to 5.0 mIU/L and a TRH stimulating test. Serum TSH levels were measured before TRH injection (TSH0) and also measured at 20 minutes (TSH1) and 40 minutes (TSH2) following intravenous injection of 400 microg TRH. Exaggerated TSH response above 30 mIU/L following TRH injection was diagnosed as SH. Group 1 was composed of poor responders (subgroup A), patients with polycystic ovary syndrome (subgroup B) and patients with WHO group II anovulation except poor responder or polycystic ovary syndrome (subgroup C). RESULTS: The prevalence of SH was significantly higher in group 1 of 46.2% (18/39) compared with 7.4% (2/27) in group 2 (P=0.001). TSH0, TSH1, and TSH2 levels were significantly higher in group 1 than the corresponding values in group 2 (P<0.001, P<0.001, P<0.001). In group 1, TSH1 and TSH2 levels were significantly lower in subgroup C compared with those in subgroup A and B (P=0.008, P=0.006, respectively). CONCLUSION: TRH stimulation test had better be performed in infertile women with ovulatory disorders who have TSH levels between 2.5 and 5.0 mIU/L for early detection and appropriate treatment of SH.

Effects of adenohypophysis function after treating with thyrotropin releasing hormone in patients with brain trauma / 中国生化药物杂志

Objective To analyze the effects of adenohypophysis function after treating with thyrotropin releasing hormone and its clinical significance in patients with brain trauma. Methods There were 22 cases with traumatic brain injuries from July 2010 to September 2012 in Chinese people's Liberation Army nine eight hospital,after injuried within 4 to 12 hours,then 1 1 cases who were given thyrotropin-releasing hormone(TRH)were selected as experimental group,while 1 1 cases who were given the same amount of isotonic saline were selected as control group,then the score of GCS, ICS,RLS85 and the improvement of adenohypophysis function were observed. Results After treatment,the score of glasgow coma scale (GCS ), innsbruck coma scale (ICS),and the reaction level scale (RLS85)between two groups were significantly increased in three days compared with before treatment,and within three days after injury situation,the improvements of ICS and RLS85 in experimental group were better than control group(P<0.05 ). Compared with control group,the levels of each gland pituitary hormone in experimental group were significantly increased(P<0.05 ),and on the third day,the growth hormone (GH)was reduced significantly,finally 50%of that in control group. Conclusion Patients with brain injury treated with thyrotropin releasing hormone,has no significant adverse reactions,with the characteristics of safe and effective.

Effects of Ramosetron on Gastrointestinal Transit of Guinea Pig

BACKGROUND/AIMS: A selective 5-hydroxytryptamine (5-HT) type 3 receptor antagonist, ramosetron, inhibits stress-induced abnormal defecation in animals and is currently used as a therapeutic drug for irritable bowel syndrome with diarrhea. The aim of this study is to investigate the effect of ramosetron on altered gastrointestinal (GI) transit. METHODS: Male guinea pigs weighing approximately 300 g were used. The effect of ramosetron was investigated on altered GI transit induced by thyrotropin-releasing hormone (TRH), 5-HT, or mustard oil (MO). GI transit was evaluated by the migration of charcoal mixture from the pylorus to the most distal point, and expressed as a percentage (%) of charcoal migration (cm) of the total length of total small intestine (cm). RESULTS: The average charcoal transit was 51.3 +/- 20.1% in the control (vehicle) group, whereas in the ramosetron group charcoal moved 56.6 +/- 21.9%, 46.9 +/- 9.14% and 8.4 +/- 5.6% of the total small intestine at the concentrations of 10, 30 and 100 microg/kg, respectively. GI transit after administration of TRH (100 microg/kg), 5-HT (10 mg/kg) or MO (10 mg/kg) was accelerated compared to vehicle (5-HT, 94.9 +/- 9.22%; TRH, 73.4 +/- 14.7%; MO, 81.0 +/- 13.7%). Ramosetron inhibited GI transit altered by 5-HT, TRH or MO. CONCLUSIONS: Ramosetron modulated GI transit. We suggest that ramosetron may be therapeutically useful for those with accelerated upper GI transit.

Alterations of serum levels of three kinds of promote hormone releasing hormones in patients with fibromyalgia / 中华神经科杂志

ObjectiveTo explore alterations of serum levels and clinical significance of corticotropin releasing hormone (CRH), thyrotropin releasing hormone (TRH) and gonadotropin releasing hormone (GnRH) in patients with fibromyalgia (FM). MethodsA total of 55 subjects participated in this study: 29 healthy volunteers and 26 patients with FM recruited from Department of Neurology, the First Affiliated Hospital of Anhui Medical University from June 2009 to October 2010.The depression rate was assessed by Hamilton Depression Rating Scale-17. ELISA was used for the detection of the serum levels of CRH, TRH and GnRH.Normal distribution quantitative data were described by the (-x) ± s and tested by independent sample t-test. Non-normal quantitative data were described by interquartile range and tested by independent Mann-Whitney.The diagnostic specificity and sensitivity of 3 kinds of hormones test were analyzed by receiver operator characteristic ( ROC ) curve, and the Spearman correlation was used for analysis of hormone levels and age, gender, tenderness, pain degree and depression severity.Results Compared with the control (70. 0(48.7,78.0) ng/L), the fibromyalgia patients had obviously increased CRH (271.9 (210.9,326.5) rg/L, x2 =6.408, P＜0. 01) , and significantly higher TRH ((82.7 ±6. 9 ) ng/L vs ( 87. 2 ± 6. 8 ) ng/L, t = 2. 560, P ＜ 0. 05, respectively) and GnRH ( ( 18. 2 ± 0. 9 ) ng/L vs ( 19. 9 ± 1.6)ng/L,t =5. 324, P ＜0. 01, respectively). The serum concentrations of the CRH, TRH and GnRH were positively correlated with pain intensity and numbers of tenderness respectively, and those of the CRH and GnRH were positively correlated with depressive degree either. The areas under the ROC curve in the CRH, TRH and GnRH, evaluating the sensitivity and specificity for diagnosis of fibromyalgia, were respectively 1. 000, 0. 684 and 0. 854. ConclusionsThe FM patients had an increased secretion of CRH,TRH and GnRH. CRH might serve as the adjunctive criteria for the diagnosis of FM.

Expression and significance of TRH-R1 and TRH-R2 in the testis of EDS-treated adult rats / 解剖学报

ObjectiveTo investigate the expression of thyrotropin-releasing hormone receptor (TRH-R) type-1and type-2 in ethane dimethanesulphonate (EDS)-treated rat testis, and to discuss the significance of its expression in Leydig cells.Methods To make the injured testis Leydig cells rat model with EDS treatment. Western blotting, immunohistochemical ABC and immunofluorescence double labeling methods were used to detect the expression and location of TRH-R1 and R2 in the testicular tissues of EDS-treated-day 2,day 7,day 14,day 21 and day 28 rat mode, respectively. Results Western blotting results showed that the positive immunochemical staining was not found in the testicular tissues of the EDS-treated day 2 to day 14, on the other hand,they were found in EDS-treated-21 day and EDS-treated-28 day. Immunohistochemistry demonstrated that TRH-R1 and R2 expressed in the spindle-shaped cells reappeared around seminiferous tubules of post-EDS 21 days and 28 days groups. Immunofluorescence double labeling confirmed that these TRH-R1 and R2 positively stained cells were newly regenerated progenitor Leydig cells.Conclusion TRH-R1 and R2 are involved in the regeneration of Leydig cells in EDS-treated rat testis, and they may exert functions in the proliferation and differentiation of adult type Leydig cells.

Experimental Study of Thyrotropin-Releasing Hormone for the Treatment of Acute Spinal Cord Injury / 中华骨科杂志

Purpose: To confirm the therapeutic effects of thyrotropin-releasing hormone(TRH) on the experimental spinal cord injury. Method: Wistar rats were subjected to incomplete spinal cord injury using the modified Allen method. The effects were observed by means of neurologic scoring, quantitative enzyme histocytoehemistry、quantitative immunohistocytochemistry and electron microscopy. Results: 1) The treated group exhibited significantly higher scores than the control group. 2) Acetylcholinesterase (AchE) activity of anterior horn cells in the treated group was higher than that of the control group invarious time, and its activity restored to normal level two weeks after injury; Acid phosphatase(AePase) activity was lower than that of the control group in various time. and its activity restored to normal level four weeks after injury. The content of Nissl's bodies in anterior horn cells in the treated group was higher than that of the control goup one week after injury. 3)The number of axon in a certain area of spinal white matter in the treated group was more than that of the control group. 4)Ultrastructural observation showed that both the nerve tissue injury and the extent of hemorrhage were milder in the treated group than that of the control group. Conclusion: The therapeutic effects of TRH on the spinal cord injury" are shown not only in the improving recovery of motor function, but also in the morphology.

The Effect of Thyrotropin Releasing Hormone on the Somatosensory Evoked Potentials and the Ultrastructure of Myelinated Nerve Fibers in Injuried Spinal Cord

The purpose of this study was to determine the effect of treatment with thyrotropin releasing hormone(TRH) on the somatosensory evoked potentials(SSEPs) and ultrastructures of myelinated nerve fibers in injured spinal cords. Spinal cords of cats were injured expermentally at the second lumbar vertebra level with 20gm-20cm(400gm-cm) impact force using modified Allen's weight drop method. The animals were treated with TRH(2mg/Kg, bolus, then 2mg/Kg/hour, IV, for 4 hours) 1 hour after injury. SSEPs were checked serially in both treated and untreated groups for 24 hours. And the fine strucures of myelinated nerve fibers in the white matters were observed in electronmicroscope before and after the injury in both groups. In treated groups, the inital positive waves were re-elicited 3 hours after injury which was eliminated immediately after injury. Fine structure of the myelinated nerve fibers were changed progressively. With time after injury, the myelinated nerve fibers showed enlarged periaxonal spaces, irregulary contoured axons, and disarray of myelin sheaths. By 4 hours after injury, there appeared marked separation and disrray of myelin sheaths, and mitochondria and neurofibrils in axoplasm showed serve degeneration. The result of this study suggested that TRH has a beneficial effect on the re-elicitation of SSEP's and the preservation of myelinated nerve fibers in the acute stage of spinal cord injury.

Comparison of thyrotropin relasing hormone and naloxone in their antagonism to morphine / 第三军医大学学报

Thyrotropin releasing hormone (TRH) and naloxone were compared in their antagonism to the effects of analgesia,addicton-induction,movement restatraining,respiration depression,LD50:etc of morphine.It was found that TRH was entirely different from naloxone in that it was not antagonistic at all to the morphine effects mentioned above.So TRH would be a better choice than naloxone in the treatment of traumatic shock.

Effects of TRH on Lipid Peroxidation in Spinal Cord Injury in Rat / 第三军医大学学报

The effects of thyrotropin releasing hormone (TRH) on lipid peroxidation in spinal cord injury in rats were studied. It was found that TRH (0.2 mg/kg, 0.6mg/kg, 2.0mg/kg bolus, followed by the same doses/h over 4 h, iv) could inhibit lipid peroxidation of the injuried spinal cord, decrease malondialdehyde (MDA)production and significantly increase superoxide dismutase (SOD) activity in a dose-dependent manner. The results indicate that the antioxidant effects of TRH are the result of increase of SOD activity. TRH might be an effective free radical scavenger.

The Effect of Thyrotropin Releasing Hormone on somatosensory Evoked Potentials in Cats with Spinal Cord Injury

The therapeutic goal for the spinal injury has been focused on preventing the secondary ischemic changes because of the poor regeneration of human spinal cord. Naloxone, an antagonist of endogenous opiates, has been clinically used for the purpose of preventing ischemic change and improving the recovery of neurological function after spinal injury. Recently, thyrotropin releasing hormone(TRH), a hypothalamic hormone inducing the thyrotropin secretion in anterior pituitary gland, has been known as a potent stimulator of cardiovascular functions in shock and the neurologic recovery in injuries of central nervous system, however, its underlying mechanism is still obscure. The present study was designed to determine whether TRH was also effective to improve the experimentally induced spinal injury as naloxone did, Somatosensory evoked potentials(SEPs) have used as an index for recovery of neurological function after the spinal injury which was induced by the 400gm.cm contusion of the T-7 spinal level in cats. The results are summarized as follows : 1. SEPs abolished soon after spinal contusion were reappeared 3 hours after injury when either of naloxone(10mg/kg) or TRH(4mg/kg) was administrated intravenously. Its recovery was completed after 24 hours. 2. The recovery rates of SEPs after treatments of naloxone and TRH were 62.5% and 64.7% of experimental animals, respectively. In conclusion, the present studies confirm the therapeutic benefit of TRH in experimental spinal injury and demonstrate that it is superior to treatment with naloxone. Further studies would be needed to explain the underlying mechanism of TRH effects.

Effect of thyrotropin-releasing hormone (TRH) on endotoxic shock in rats / 中国药理学通报

The effect of TRH on endotoxic shock in rats was studied, iv 0. 22-2 mg ?kg-1 TRH significantly reversed hypotension induced by iv coli E. endotoxin (40 mg ?kg-1) into rats and caused a 4. 2 kPa rise in mean arterial pressure (MAP). MAP after TRH administered could be stablized over a higher level than control for 30 min and maintained for 3 h during observation. Interestingly enough, the MAP rose gradually in TRH-treated rats as contrast with increasingly falling of that in control group during the late shock. TRH also improved 24 h sur-vival of shock rats. The dose-response relationship could be observed between 0. 22 ~0. 67 mg ?kg-1 TRH and disappeared over a highest dose (2 mg ?kg-1). It was shown that the best dose to reverse hypotension and to improve survival was 0. 67 mg ?kg-1 TRH. Naloxone 2 mg ?kg-1 showed the nearly same effect as 0. 22 mg ?kg-1 TRH in increasing MAP, but the former had higher 24 h survival of rats than the later.

The effect of thyrotropin releasing hormone on rehabilitation of stroke patients / 日本温泉気候物理医学会雑誌

In order to analyze the influence of thyrotropin releasing hormone (TRH) on rehabilitation process of stroke Patients, the comparison of functional gain and length of hospital stay was made between eight patients treated with TRH (TRH group) and 11 age and sex matched ones without TRH (control group). Using Social Maturation Scale (Takenshiki, SMS) and Motor Age Test for trunk and lower extremities (MoA), the patients were assessed at the admission, 2 and 3 months after the admission and the discharge, respectively. TRH of 2mg was administered once a day by intravenous drip injection for 10 days between 2 and 3 months after the admission. The gain of SMS score between 2 and 3 months after the admission was larger in the TRH group than in the control group, especially that of interpersonal skills. The gain of MoA score was not different between the two groups. Compared to the control group (5.3 months), the length of hospital stay was significantly short in the TRH group (4.2 months). However, functional gain during inpatient-rehabilitation was not different between the two groups. It is assumed that TRH is effective to shorten the course of stroke rehabilitation.

EFFECT OF INTRACEREBROVENTRICULAR INJECTION OF TRH ON INTRAGASTRIC PRESSURE IN RATS / 中国药理学通报

In the present study, the results were as follows: ( 1 ) Thyro-tropin-releasing hormone ( TRH ) injected into the intracerebroven-tricle increased intragastric pressure & evoked the phasic contraction of stomach significantly. ( 2 ) The increased response was decreased by bilateral destruction of dorsa. motor nucleus of vagus. ( 3 ) The increase was abolished completely by either vagotomy or atropine.The aforementioned results indicate that the action of dors. motor nucleus of vagus is partly involved the central mechanism of gastric movement induced by TRH & the vagal is the efferent pathway.

Clinical Study on the Effect of TRH in Patients with Prolonged Mild Disturbance of Consciousness

Authors report the clinical study on the usefulness of thyrotropin-releasing hormone tartrate(TRH-T) in the treatment of mild disturbance of consciousness. 20 patients suffering head trauma, subarachnoid hemorrhage, and intracerebral hemorrhage were given TRH-T intravenously for ten days. TRH-T was effective for the patients in whom the consciousness disturbance was mild, the duration in fixed consciousness level was short, and the brain was not distorted on CT scan. These features were most prominent in patients with subarachnoid hemorrhage. Three was no significant side effect, and TRH-T turned out to be safe.

The Pharmacokinetics of Thyrotropin-releasing Hormone in Rabbits / 第二军医大学学报

The pharmacokinetics of thyrotropirrreleasing hormone (TRH) made in China was studied in rabbits. TRH concentrations in plasma, urine and various tissues were measured by RIA. After intravenous injection of TRH, the plasma concentration-time curve was shown to fit a two compartment open model with the following pharmacokinetic parameters: 0.8 mg/kg, T1/2?=0.551 min, T1/2? = 9.374 mm, VI = 3.018 ml/kg, Vb = 22.659 ml/kg and AUC = 0.479g. L-1. m-1; 2.0mg/kg, T1/2? = 0.629 mm, T1/2?= 9.734 min, VI = 5.135 ml/kg, Vt = 28.848 ml/kg, and AUC = 0.962g. L-1. m-1; 5.0mg/kg, T1/2? =0.720 min, T1/2?= 10.738 min, VI = 6.120 ml/kg, Vb = 31.928 ml/kg and AUC=2.540 g. L-1. m-1. TRH was distributed widely in tissues and concentrated mainly in the kidney and pituitary. TRH was eliminated partly by the kidney and 21.9% was excreted within 2h after intravenous injection.