Association between Free Triiodothyronine Levels and Peripheral Arterial Disease in Euthyroid Participants

This current cross-sectional study investigates the relationship between thyroid hormones and peripheral artery disease （PAD） among euthyroid Chinese population aged 40 years and above. Serum free triiodothyronine （FT3）, free thyroxin （FT4）, thyroid-stimulating hormone （TSH）, and thyroid antibodies were measured.

Free triiodothyronine level correlates with statin responsiveness in acute myocardial infarction

Background Although thyroid hormone （TH） has important effects on lipid metabolism, the relationship between TH and statin responsiveness has never been investigated. We hypothesize that TH plays an important role in statin responsiveness in patients with acute myocardial infarction （AMI）. Methods Consecutive 1091 hospitalized AMI patients in Fuwai hospital （Beijing, China） were enrolled into this current study. The study population was divided into three groups based on the intensity of statin treatment： low-intensity （n = 221）, moderate-intensity （n = 712） and high-intensity （n = 158）. Lipid levels were measured after statin therapy lasting for 10-14 days. The association between TH, lipid profile levels and achievement of low-density lipoprotein cholesterol （LDL-C） lowering goals was explored in patients with AMI on statin therapy. Results By general linear analysis, a significant linear trend between free triiodothyronine （FT3） and LDL-C level （linear coefficient r = -0.082, P = 0.001） and FT3 and total cholesterol （TC） level （r = -0.105, P = 0.031） was observed in the moderate-intensity statin group. A more apparent linear trend was detected in the high-intensity statin group （for LDL-C： r = -0.113, P = 0.005; for TC： r = -0.172, P = 0.029, respectively）. However, no significant correlation was observed in the low-intensity statin group. Compared with the low-FT3 group （defined as FT3 〈 1.79 pg/mL）, the OR （95% CI） for attaining a LDL-C 〈 3.0mmol/L was found to be 2.217 （1.001–4.839） in the higher FT3 group （〉 2.95 pg/mL）. The OR （95% CI） for attaining the more intensive goal （LDL-C 〈 1.8mmol/L） was 2.836 （1.014–5.182）. Conclusions Our study reveals that variation in FT3 levels is related to the cholesterol-lowering responsiveness of statins in AMI patients. These findings suggest that low FT3 may be a factor responsible for lack of LDL-C goal attainment and patients’ poor responsiveness to statin treatment.

Triiodothyronine and breast cancer

The thyroid hormones(THs), triiodothyronine(T3) and thyroxine(T4), are essential for survival; they are involved in the processes of development, growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are involved in other diseases. The role of THs in the development and differentiation of mammary epithelium is well established; however, their specific role in the pathogenesis of breast cancer(BC) is controversial. Steroid hormones affect many human cancers and the abnormal responsiveness of the mammary epithelial cells to estradiol(E2) in particular is known to be an important cause for the development and progression of BC. The proliferative effect of T3 has been demonstrated in various types of cancer. In BC cell lines, T3 may foster the conditions for tumor proliferation and increase the effect of cell proliferation by E2; thus, T3 may play a role in the developmentand progression of BC. Studies show that T3 has effects similar to E2 in BC cell lines. Despite controversy regarding the relationship between thyroid disturbances and the incidence of BC, studies show that thyroid status may influence the development of tumor, proliferation and metastasis.

Free triiodothyronine in relation to coronary severity at different ages： Gensini score assessment in 4206 euthyroid patients

Objective To study whether free triiodothyronine （FT3） within normal range has effects on the presence and severity of coronary ar- tery disease （CAD） in different gender and age groups. Methods A total of 4206 euthyroid patients were consecutively enrolled and di- vided into CAD group （n = 3306） and non-CAD group （n = 900）. All patients underwent coronary angiography （CAG）. Gensini score （GS） was used to determine the severity of coronary artery stenosis. Severe CAD was defined as GS 〉 32 and mild CAD was defined as GS 〈 32. Logistic regression analysis and linear regression analysis were conducted to determine the association of FT3 with CAD in patients with different gender and ages. Results Concentration of FT3 was lower in patients with CAD than that in angiography-normal control group （P 〈 0.05）. In addition, concentration of FT3 was lower in severe CAD than that in mild CAD. After adjusting for traditional cardiovascular risk factors and potential confounders, FT3 was negatively correlated with the presence of CAD, but not in the old patients （〉 65 years old）. Mul- tivariable linear regression analysis showed that FT3 was negatively associated with GS in male and young patients with stable CAD, but not in the old patients. Conclusions Low FT3 within normal range was negatively associated with the presence and severity of CAD in young patients, but not in the old ones. Further studies are needed to confirm our findings.

Piezoelectric Immunoasay of Thyroidal Triiodothyronine

Are-utilizable piezoelectric crystal(PC)immunosensor for thyroidal triiodothyronine(T3)has been developed.The crystal was coated with protein A and then reacted with T3 antibody.T3 could be detect-ed in the range of 0.5x 106g/L to 10.0x 106g/L by the system.Crystal was regenerated by saturating with T3 and subsequent binding of a new anti T3 antibody layer.The T3 assay could be repeated up to 5 times using each crystal.

Cardiovascular mechanisms of thyroid hormones and heart failure:Current knowledge and perspectives

A multiple hormonal imbalance that accompanies heart failure(HF)may have a significant impact on the clinical course in such patients.The non-thyroidal illness syndrome(NTIS),also referred to as euthyroid sick syndrome or low triiodothyronine syndrome,can be found in about 30%of patients with HF.NTIS represents a systemic adaptation to chronic illness that is associated with increased cardiac and overall mortality in patients with HF.While conclusions on thyroid-stimulating hormone,free triiodothyronine,total and free thyroxine are currently unresolved,serum total triiodothyronine levels and the ratio of free triiodothyronine to free thyroxine seem to provide the best correlates to the echocardiographic,laboratory and clinical parameters of disease severity.HF patients with either hyper-or hypothyroidism should be treated according to the appropriate guidelines,but the therapeutic approach to NTIS,with or without HF,is still a matter of debate.Possible treatment options include better individual titration of levothyroxine therapy,combined triiodothyronine plus thyroxine therapy and natural measures to increase triiodothyronine.Future research should further examine the cellular and tissue mechanisms of NTIS as well as new therapeutic avenues in patients with HF.

Association between sensitivity to thyroid hormones and non-highdensity lipoprotein cholesterol levels in patients with type 2 diabetes mellitus

BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.

Free triiodothyronine level indicates the degree of myocardial injury in patients with acute ST-elevation myocardial infarction

Background Previous studies have suggested that hypothyroidism correlated with coronary heart diseases （CHD） mortality in long-term cohort, but whether the thyroid function status is associated with myocardial injury in acute ST- elevation myocardial infarction （STEMI） has not been investigated sufficiently.

Prognostic value of free triiodothyronine in patients with dilated cardiomyopathy

Background:The association between free triiodothyronine(FT3)and long-term prognosis in dilated cardiomyopathy(DCM)patients has not been evaluated.The purpose of this study was to determine whether the level of FT3 could provide prognostic value in patients with DCM.Methods:Data of consecutive patients diagnosed with DCM were collected from October 2009 to December 2014.FT3 was measured by fluoroimmunoassay.Other biochemical markers,such as free thyroxin(FT4),thyroid-stimulating hormone,red blood cell,hemoglobin,blood urea nitrogen,and serum creatinine,were tested at the same time.Follow-up was performed every 3 months.The primary endpoint was all-cause mortality.Pearson analysis was used to evaluate the correlation of FT3 and other lab metrics with DCM patients’prognosis.The association of long-term mortality in DCM and FT3 was compared using Cox hazards model.Results:Data of 176 patients diagnosed with DCM were collected.Of them,24 patients missed FT3 values and six patients were lost to follow-up.Altogether,data of 146 patients were analyzed.During the median follow-up time of 79.9(53.5-159.6)months,nine patients lost,61 patients died(non-survival group),and 85 patients survived(survival group).FT3 was significantly lower in non-survival group than that in survival group(3.65±0.83 pmol/L vs.4.36±1.91 pmol/L;P=0.003).FT3 also showed a significantly positive correlation with red blood cell and hemoglobin,negatively correlated with age,blood urea nitrogen and serum creatinine(P<0.05),respectively.Patients in the group of lower FT3 levels(FT3≤3.49 pmol/L)suffered from a higher risk of all-cause mortality(P for log-rank=0.001).In multivariate Cox regression analysis,FT3 level was significantly associated with all-cause mortality(hazard ratio:0.70,95%confidence interval 0.52-0.95,P for trend=0.021).Conclusion:Low levels of FT3 were associated with increased all-cause mortality in patients with DCM.

Thyroid peroxidase antibody positivity and triiodothyronine levels are associated with pediatric Graves'ophthalmopathy

Background:Graves'ophthalmopathy(GO)occurs commonly in children with Graves'disease(GD).However,there are limited studies on the clinical manifestations and thyroid autoantibodies in pediatric GO.The aim of this study was to investigate the prevalence and risk factors of GO in childhood GD.Methods:Clinical and biochemical data from children and adolescents with GD were retrospectively reviewed.Eighty patients under 19 years of age were included in the present study.We compared the clinical and biochemical differences between patients with and without GO.Results:Thirty-nine percent of the patients had GO,and 81%of the GO patients were females.Of these,two patients showed unilateral GO.Triiodothyronine(T3)levels were higher in GO patients than in those without GO.Anti-thyroglobulin antibody and thyroid stimulating hormone receptor antibody titers were not significantly different between the two groups.Anti-thyroid peroxidase antibody(TPO Ab)positivity was 68%in the patients with GO and only 47%in the patients without GO.In multivariate regression analysis,high T3 levels and TPO Ab positivity were related to the presence of GO.Conclusion:In children and adolescents with GD,TPO Ab positivity and high T3 levels could act as predictive factors for the presence of GO.

Association of Serum Ferritin Levels and Thyroid Hormones

Thyroid metabolism is orchestrated by the action of various minerals and trace elements including iron, iodine, selenium, and zinc. Iron deficiency, specifically deficiency in serum ferritin levels, is one of the common causes of thyroid dysfunction. Our objective was to evaluate the relationship between serum ferritin levels and circulating thyroid hormones. For this, a retrospective analysis was performed on 16,512 individuals who tested for serum levels of ferritin and thyroid profile at Vibrant America Clinical Laboratories. Subjects were stratified based on the serum levels of ferritin. Age (p −0.03232, p < 0.0001). Analysis of Linear association by Pearson’s correlation exhibited a considerable correlation between varying serum ferritin levels with all tested thyroid hormones. The study concludes that serum ferritin levels were associated with thyroid hormone synthesis and metabolism in individuals with optimal levels of circulating ferritin.

Relationship between β-amyloid protein 1-42, thyroid hormone levels and the risk of cognitive impairment after ischemic stroke

BACKGROUND Post-stroke cognitive impairment(PSCI)is not only a common consequence of stroke but also an important factor for adverse prognosis of patients.Biochemical indicators such as blood lipids and blood pressure are affected by many factors,and the ability of evaluating the progress of patients with PSCI is insufficient.Therefore,it is necessary to find sensitive markers for predicting the progress of patients and avoiding PSCI.Recent studies have shown thatβ-amyloid protein 1-42(Aβ1-42)and thyroid hormone levels are closely related to PSCI,which may be the influencing factors of PSCI,but there are few related studies.AIM To investigate the relationship between serum levels of Aβand thyroid hormones in acute stage and PSCI and its predicted value.METHODS A total of 195 patients with acute cerebral infarction confirmed from June 2016 to January 2018 were enrolled in this study.Baseline data and serological indicators were recorded to assess cognitive function of patients.All patients were followed up for 1 year.Their cognitive functions were evaluated within 1 wk,3 mo,6 mo and 1 yr after stroke.At the end of follow-up,the patients were divided into PSCI and non-PSCI according to Montreal cognitive assessment score,and the relationship between biochemical indexes and the progression of PSCI was explored.RESULTS Compared with patients with non-PSCI,the levels of Aβ1-42,triiodothyronine(T3)and free thyroxin were lower in the patients with PSCI.Repeated measures analysis of variance showed that the overall content of Aβ1-42 and T3 in PSCI was also lower than that of the non-PSCI patients.Further analysis revealed that Aβ1-42(r=0.348),T3(r=0.273)and free thyroxin(r=0.214)were positively correlated with disease progression(P<0.05),suggesting that these indicators have the potential to predict disease progression and outcome.Cox regression analysis showed that Aβ1-42 and T3 were important factors of PSCI.Then stratified analysis showed that the lower the Aβ1-42 and T3,the higher risk of PSCI in patients who were aged over 70,female and illiterate.CONCLUSION Aβ1-42 and T3 have the ability to predict the progression of PSCI,which is expected to be applied clinically to reduce the incidence of PSCI and improve the quality of life of patients.

Changes in thyroid function in patients with liver failure and their clinical significance:A clinical study of non-thyroidal illness syndrome in patients with liver failure

Background:Non-thyroidal illness syndrome(NTIS)develops in a large proportion of critically ill patients and is associated with high risk for death.We aimed to investigate the correlation between NTIS and liver failure,and the short-term mortality of patients with these conditions.Methods:The clinical data of 87 patients with liver failure were collected retrospectively,73 of them were randomly selected for an observational study and to establish prognostic models,and 14 for model validation.Another 73 sex-and age-matched patients with mild chronic hepatitis were randomly selected as a control group.Serum free triiodothyronine(FT3),free thyroxine(FT4),and thyroid-stimulating hormone(TSH)were measured.The clinical characteristics of patients with liver failure and NTIS were analyzed.The follow-up of patients lasted for 3 months.Additionally,the values for predicting short-term mortality of model for end-stage liver disease(MELD),Child-Turcotte-Pugh(CTP),chronic liver failure-sequential organ failure assessment(CLIF-SOFA)scores,FT3-MELD model,and FT3 were evaluated.Results:The observation group had significantly lower FT3(2.79±0.71 vs.4.43±0.75 pmol/L,P<0.001)and TSH[0.618(0.186-1.185)vs.1.800(1.570-2.590)mIU/L,P<0.001],and higher FT4(19.51±6.26 vs.14.47±2.19 pmol/L,P<0.001)than the control group.NTIS was diagnosed in 49 of the patients with liver failure(67.12%).In the observation group,patients with NTIS had a higher mortality rate than those without(63.27%vs.25.00%,P=0.002).Across the whole cohort,the 3-month mortality was 50.68%.The international normalized ratios(INR)were 2.40±1.41 in survivors and 3.53±1.81 in deaths(P=0.004),the creatinine(Cr)concentrations were 73.27±36.94μmol/L and 117.08±87.98μmol/L(P=0.008),the FT3 concentrations were 3.13±0.59 pmol/L and 2.47±0.68 pmol/L(P<0.001),the MELD scores were 22.19±6.64 and 29.57±7.99(P<0.001),the CTP scores were 10.67±1.53 and 11.78±1.25(P=0.001),and the CLIF-SOFA scores were 8.42±1.68 and 10.16±2.03(P<0.001),respectively.FT3 was negatively correlated with MELD score(r=−0.430,P<0.001).An FT3-MELD model was established by subjecting FT3 concentration and MELD score to logistic regression analysis using the following formula:Logit(P)=−1.337×FT3+0.114×MELD+0.880.The area under the receiver operating characteristic(ROC)curve was 0.827 and the optimal cut-off value was 0.4523.The corresponding sensitivity and specificity were 67.6%and 91.7%.The areas under the ROC curve for FT3 concentration,MELD score,CTP score,and CLIF-SOFA score were 0.809,0.779,0.699,and 0.737,respectively.Conclusions:Patients with liver failure often develop NTIS.FT3-MELD score perform better than CTP and CLIF-SOFA scores in predicting mortality in patients with liver failure.Thus,the FT3-MELD model could be of great value for the evaluation of the short-term mortality of such patients.

L-tyrosine improves neuroendocrine function in a mouse model of chronic stress

Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.

Relationship between Free Thyroxine and Islet Beta-cell Function in Euthyroid Subjects

Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.

Changes in serum thyroid hormone levels and thyroid gland activity of artificially maturing female Japanese eel (Anguilla japonica)

In order to evaluate the involvement of the thyroid gland in reproduction, thyroid functioning was described in female cultivated Japanese eel (Anguilla japonica) in progressive stages of sexual maturation induced by chum salmon pituitary homogenate (SPH) treatment. Serum thyroid hormones, thyroxine (T4) and triiodothyronine (T3) were also measured in each stage. Thyroid gland activity (epithelial cell height) was high before SPH injection (previtellogenic stage), further increasing at the early vitellogenic stage, thereafter decreasing to late vitellogenic and migratory nucleus stages. The profiles of both T3 and T4 changed during vitellogenesis, being high during previtellogenic and early vitellogenic stages, and subsequently declining, thus mimicking thyroid gland activity. These results suggest that the thyroid has relation with eel ovarian development during artificial maturation.

EFFECTS OF ACUPUNCTURE ON THE PITUITARYTHYROID AXIS IN RABBITS WITH FRACTURE

PURPOSE: To observe the effects of acupuncture on the pituitary-thyroid axis in rabbits with fracture. METHOD: 36 male rabbits with a 3-mm width experimental defect in the middle segment of the left radius were randomly divided into the treatment group and control group, and the changes in serum T3, T4 and TSH contents in different weeks were investigated. RESULTS: Serum T3, T4 and TSH contents in the treatment group all were higher than those in the control group, with statistically significant differences in the contents of T4 and TSH in the second week and T3 content in the fourth week (P

Evaluation of Thyroid Hormones Levels in Libyan Patients with Chronic Renal Failure before and after Maintenance Hemodialy

Data from recent studies revealed that kidney diseases might affect the thyroid function in various ways. A variety of alterations in thyroid hormone levels and metabolism have also been reported in patients with chronic renal failure (CRF) in some studied population. In addition, it was reported that serum levels of both T3 and T4 might alter immediately after a hemodialysis (HD) treatment than before. Therefore, this study was aimed to investigate the level of triiodothyronine (T3) and thyroxine (T4) in CRF Libyan patients before and after HD. This study was carried out on 46 CRF patients (30 males and 16 females) with a mean age of 47.46 ± 15.75 years. These patients were treated at the hemodialysis unit of Educational Central Zelitin Hospital, Zelitin, Libya. None of these patients apparently have any thyroid problems and no history of drug intake that may affect thyroid function. Blood samples were taken from each patient to measure serum levels of T3 and T4, before and after HD. In addition, the effects of several variables including age, gender, body mass index (BMI), presence of both hypertension and, diabetes mellitus and duration of kidney dialysis on serum levels of T3 and T4 before and after HD were also studied. After HD, there was a statistically significant increase in the serum levels of T3, T4. The age, gender, BMI, duration of kidney dialysis and the presence of hypertension and diabetes mellitus did not have any significant effect on the serum level of T3 and T4 before and after HD. However, the serum levels of T3 and T4 were still in the normal range in these examined patients either before or after HD. From these findings, it can be concluded that these CRF patients may be in a euthyroid state, because the serum levels of T3 and T4 were in the normal range. In addition, HD was seemed to improve the T3 and T4 thyroid hormone concentrations, suggesting that HD might activate the secretion of thyroid gland and catabolism. The other variables did not play any role in thyroid hormone levels in these patients either before or after HD. It is highly recommended that large scale evaluation of thyroid hormone levels in Libyan CRF patients is performed by more patients, especially elderly patients.

聊城市妊娠妇女甲状腺激素参考区间的建立

目的：建立本实验室妊娠妇女促甲状腺激素（TSH）、游离甲状腺素（FT4）和游离三碘甲状腺原氨酸（FT3）的参考区间。方法：将826例妊娠妇女分为妊娠早中晚期3组，用Beckman access2化学发光分析仪及其配套试剂检测TSH、FT4、FT3，初步建立参考区间。结果：TSH参考区间：妊娠早期0.11～2.88 uIU/ml，妊娠中期0.24～3.31 uIU/ml，妊娠晚期0.55～3.78 uIU/ml。FT4参考区间：妊娠早期0.69～1.13 ng/dl，妊娠中期0.56～0.99 ng/dl，妊娠晚期0.49～0.89 ng/dl。FT3参考区间：妊娠早期2.67～4.03 pg/ml，妊娠中期2.35～3.56 pg/ml，妊娠晚期2.08～3.25 pg/ml。结论：建立了本院妊娠妇女血清TSH、FT4、FT3的参考区间，该区间与Beckman access2化学发光分析仪说明书提供的参考区间有差异。各实验室应根据不同仪器和人群等建立TSH、FT4、FT3的参考区间。

Effect of estradiol-17β on pituitary-thyroidal axis of Japanese eel (Anguilla japonica)

The effect of estradiol-17β (E2)treatment on the pituitary-thyroidal axis has been investi- gated in female Japanese eels in seawater. The eels were injected with 1 mg/kg body weight (BW) weekly for two to eight weeks; another group was treated with 5 mg/kg BW weekly for eight weeks and sacrificed three days after the last injection. In the pituitary, using RT-PCR systern, the thyroid stim- ulating hormone 3 subunit mRNA (TSHβ MRNA) level is slowly increased in the low-dose E2 treatment group. A significant increase in values occurred after eight weeks E2 injections. The histological structure of the thyroid follicles suggests a hypo-activity as shown by a reduced epithelial cell height in eels injected with E2 after six and eight times, and eventually reached a minimum level after eight weeks. Using ra- dioimmunoassay of thyroxine (T4),triiodothyronine (T3) in the serum, a slowly decrease of both hor- mones is demonstrated. On the other hand, the TSHβ mRNA level is significantly increased from initial in the high-dose E2 treatment group. The histological structure of the thyroid follicles suggests a hypo- activity, and a sharp decrease of the both hormones is also indicated. These data suggest that the expres- sion of TSHβ mRNA level is increased and thyroid hormone release is depressed by E2, the effects de- pend upon E2 inection period and dose. Furthermore, E2 could not directly influence the TSHβ mRNA expression and, TSH transcription might be controlled by a negative feedback of thyroid hormone.