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 n...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.展开更多
Objectives To evaluate the effect of thyroid hormone therapy with low dose of thyroxin on cardiac function in elderly patients with heart failure and sick euthyroid syndrome. Methods Forty-seven patients (33 males and...Objectives To evaluate the effect of thyroid hormone therapy with low dose of thyroxin on cardiac function in elderly patients with heart failure and sick euthyroid syndrome. Methods Forty-seven patients (33 males and 14 females, mean age 85.9+4.6 years,ranging from 80 to 99 years) with chronic heart failure (NYHA Ⅱ-Ⅳ) and low triiodothyronine (T3) state were randomly allocated to the treatment group or control group. The treatment group patients received oral administration of levothyroxine sodium (Euthyrox) 25-50mg/d in addition to conventional therapy of heart failure, whereas patients in control group were given conventional therapy only. Serum level of total T3 (TT3), free T3 (FT3), total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were determined. For both groups, left ventricular ejection fraction (LVEF) and stroke volume (SV) were assessed by two-dimensional echocardiography before and at 8 weeks after treatment. The changes of these parameters after the treatment were evaluated by adjusting heart rate in the two groups. Results The reduced serum T3 level in the treatment group was corrected after thyroid hormone therapy,and these patients had a significant improvement in cardiac function after treatment. By contrast, in the control group only changes of serum TT3 and TT4 levels and SV and LVEF after treatment were statistically significant. The heart rate-adjusted mean SV and LVEF in both groups were also increased, which was significantly greater in the treatment group than in the control group. Conclusion In the elderly patients with heart failure and sick euthyroid syndrome, addition of thyroxine at a low dosage to the conventional treatment could effectively improve the low T3 state and cardiac function independent of changes of heart rate.展开更多
Introduction: Down syndrome (DS) is the most common chromosomal abnormality causing mental handicap in humans. Children with DS have significant medical problems and developmental delay which are further impaired by h...Introduction: Down syndrome (DS) is the most common chromosomal abnormality causing mental handicap in humans. Children with DS have significant medical problems and developmental delay which are further impaired by hypothyroidism. Those clinical features are potentially improved by using thyroxine replacement therapy. Objectives: To examine the evidence of effectiveness (motor & mental development) and safety of thyroxine supplementation in the treatment of SH and CH in children with DS. Methods: Several medical data bases (MEDLINE, EMBASE, CINAHL, Cochrane, Clinical Trials Gov, Essential Evidence and Google) were searched until 20 October, 2011, for randomized control trials (RCTs) that had examined thyroxine’s effectiveness and safety in the treatment of SH or CH in children with DS. Results: There were two high quality RCTs that examined thyroxine in the treatment of CH in children with DS, and no RCTs were found to have examined the effectiveness of thyroxine for SH in children with DS. Conclusion: The RCT which met our inclusion criteria provides the reliable evidence in recommending thyroxine for the treatment of CH in children with DS which is similar to the guidelines for general population. The absence of RCTs examining the treatment of SH in Children with DS indicates the need to conduct such trials.展开更多
The present study deals with the effect of exogenous treatment of O. niloticus females with L-thyroxine (T4) on the development of the digestive system during larval rearing, and its subsequent effect on larval growth...The present study deals with the effect of exogenous treatment of O. niloticus females with L-thyroxine (T4) on the development of the digestive system during larval rearing, and its subsequent effect on larval growth and survival. The development of the digestive tract and accessory glands was investigated histologically and histochemically in the developing O. niloticus larvae, from control and T4-treated spawners. During yolk-sac absorption, the digestive system of the fish underwent further differentiation and the rudimentary alimentary canal became segmented into four different histological regions: the buccopharynx, oesophagus, stomach and intestine. The injection of females O. niloticus with thyroxine (1 or 10 μg T4/g BW) greatly enhanced the development of the digestive tract and accessory glands of larvae as indicated by the quantitative and qualitative changes of the mucus composition from predominantly neutral to a mixture of neutral and acid mucosubstances, or acid mucosubstances occurred during the rearing period for the larvae produced from T4-treated females. This may be due to the direct effect of exogenous thyroxine, which might have been transferred from maternal circulation into the oocytes and larvae, on the synthesis of proteins, which increased with larval development. Thus, thyroxine directly or indirectly improved O. niloticus larval growth, since a marked increase in both, length and weight of larvae occurred during the experimental period. In addition, larvae from treated females also gave a significantly higher survival rate than that of control. It could be concluded that exogenous T4 in maternal circulation might have been transferred into oocytes and larvae. The transferred thyroid hormone appears to play some role in the early development of larvae and may confer a distinct advantage for the growth of the offspring of the Nile tilapia, O. niloticus.展开更多
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 comm...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.展开更多
AIM: To investigate the impact of hypothyroidism and thyroxine therapy on insulin sensitivity in patients with overt hypothyroidism.METHODS: The study included twenty seven overtly hypothyroid and fifteen healthy euth...AIM: To investigate the impact of hypothyroidism and thyroxine therapy on insulin sensitivity in patients with overt hypothyroidism.METHODS: The study included twenty seven overtly hypothyroid and fifteen healthy euthyroid South Western Asian females.Both groups had matching age and body mass index.Physiological and pathological conditions as well as medications that may alter thyroid function,glucose homeostasis or serum lipids were ruled out.Serum thyrotropin(TSH),free tetraiodothyronine(FT4),free triiodothyronine(FT3),fasting insulin(FI),fasting plasma glucose(FPG),total cholesterol and triglycerides were measured before and six months after initiating thyroxine therapy for hypothyroid patients and once for the control group.Insulin resistance(IR) was estimated using homeostasis model assessment(HOMA-IR) and Body mass index(BMI) was calculated.RESULTS: Both study groups,hypothyroid patients and euthyroid control subjects,had matching age and body mass index(P-value 0.444,0.607 respectively).No significant difference was found between the hypothyroid patients and the euthyroid control group regarding fasting plasma glucose,fasting insulin,insulin resistance,total cholesterol and triglycerides(P-values 0.432,0.621,0.883,0.586,0.05 respectively).In the hypothyroid patients,triglycerides showed direct correlation to TSH and inverse correlation to FT3.Similarly total cholesterol inversely correlated to FT3 but its direct correlation to TSH did not reach statistical significance.After thyroxine replacement and reaching an euthyroid state as confirmed by clinical and laboratory data,there was no significant change in fasting plasma glucose,insulin resistance or triglyceride level(P-value 0.216,0.204,0.175 respectively) while total cholesterol significantly decreased(P-value 0.043) and fasting insulin significantly increased(P-value 0.047).CONCLUSION: Hypothyroidism has no impact on insulin sensitivity.Correction of hypothyroidism is not associated with a significant change of insulin sensitivity or triglycerides,but with a significant reduction of total cholesterol.展开更多
Out of 100 cases of intractable schizophrenia,57 cases were in the group ofComputer-Controlled Electric Acupuncture (CCEA) and 43 in the control group.The therapeutic re-sults showed that clinically CCEA had a remarka...Out of 100 cases of intractable schizophrenia,57 cases were in the group ofComputer-Controlled Electric Acupuncture (CCEA) and 43 in the control group.The therapeutic re-sults showed that clinically CCEA had a remarkably effective rate of 40. 35% on refractoryschizophrenia,which had much better curative effects than those in the control group.Through dy-namic evaluation of brief psychiatric rating scale (BPRS),negative symptom scale (SANS) and posi-tive symptom scale (SAPS) for both groups before,during and after treatment,the results indicatedthat in CCEA group the scores of BPRS,SANS and SAPS after treatment were much less than thosebefore treatment,which were remarkably different from those in the control group (P【0.01).Lab-oratory examination of thyroxin and androgen of patients in both groups before and after treatmentfound a significant result.展开更多
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 chro...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.展开更多
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 week...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.展开更多
The effects of khat on the hormonal levels have been established;however, the effects on human beings are controversial. The aim of our study was to investigate the possible effects of khat on the levels of serum thyr...The effects of khat on the hormonal levels have been established;however, the effects on human beings are controversial. The aim of our study was to investigate the possible effects of khat on the levels of serum thyroid hormones, testosterone, estradiol (E2), prolactin and cortisol in men. A total of 50 blood samples were collected from healthy males who referred to chew khat for more than 10 years and analyzed for the above hormones. The results were compared to the hormonal levels of 35 non khat chewers. Chewing khat causes significant increases in the testosterone (P < 0.03), prolactin (P < 0.05), E2 (P < 0.00005), FT3 (P < 0.04), and TSH (P < 0.05) levels. No significant differences were found in the serum level of FT4 between the two groups. The level of cortisol were significantly lower (P < 0.001) in the khat chewers group compared to the control group. This study suggests that khat chewing can cause reduction in the cortisol level, which may cause increases of testosterone, prolactin and E2. In addition, chewing khat increases the level of TSH and FT3 serum levels. Therefore, khat may contribute to the relevant disorders caused by abnormal levels of the studied hormones in the people who are chewing展开更多
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...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.展开更多
Vitamin D3 after its entrance in the organism undergoes hydroxylation on C-25 carbon atom by the action of microsomal liver enzymes giving the metabolite 25 hydroxyvitamin D3 (25OHD3). The function of microsomal liver...Vitamin D3 after its entrance in the organism undergoes hydroxylation on C-25 carbon atom by the action of microsomal liver enzymes giving the metabolite 25 hydroxyvitamin D3 (25OHD3). The function of microsomal liver enzymes is influenced in some specified states by hormones or drugs. It has approved that thyroxin is a potent stimulator of these enzymes while allopurinol suppresses their function. The aim of this issue is to examine 25OHD3 plasma levels in thyrotoxic subjects and in those pretreated with allopurinol on the base of the afford mentioned data. In a first phase 25OHD3 plasma levels were estimated in thyrotoxic subjects against euthytoid healthy controls. In a second phase lmg vitamin D3 was injected intravenously (i.v.) in thyrotoxic subjects and in healthy euthyroid controls. 25OHD3 plasma levels were measured before and in post injection period in six hours intervals for 48 hours. In a third phase a couple of subjects one thyrotoxic and one euthyroid healthy control pretreated both with allopurinol injected lmg of vitamin D3 i.v. In all studied subjects 25OHD3 plasma levels were measured before and in post injection period in six hours intervals for 48 hours. The pre and post injection 25OHD3 plasma levels measured the size of activity of liver enzyme responsible for bioactivation of vitamin D3. In the first phase was indicated that 25OHD3 plasma levels were lower in thyrotoxic subjects comparing with that of euthyroid healthy controls (p 3 in thyrotoxic subjects was 2,5 to 8 times faster comparing with euthyroid healthy controls. In the third phase was shown that allopurinol decreases the activity of liver enzymes function as regard the bioactivation of vitamin D3. The bioactivation of vitamin D3 is accelerated in thyrotoxicosis compared with that in euthyroid state. This phenomenon produces low 25OHD3 plasma levels in thyrotoxic subjects which initially may be normal or slightly increased depended from the vitamin D3 status in the thyrotoxic subjects. By continuous stimulatory action of increased thyroid hormones on liver enzymes the 25OHD3 plasma levels earlier or later decline in levels of hypo-or avitaminosis D3. The previously described biological events may explain the decreased intestinal calcium absorption of vitamin D3 and the osteomalacic component found in a percentage of thyrotoxic bone histology. For the blocking effects of allopurinol on liver enzymes function and possibly of other pharmaceutical products in relation to vitamin D3 bioactivation, available data are still lacking.展开更多
Objective To investigate the relationship between intrauterine growth retardation (IUGR) and endocrine parameters so as to assess the effects or the main endocrine ractors on IUGR. The concentrations of growth hormone...Objective To investigate the relationship between intrauterine growth retardation (IUGR) and endocrine parameters so as to assess the effects or the main endocrine ractors on IUGR. The concentrations of growth hormone(GH), insulin, T3, T4 and TSH were measured in umbilical cord blood, amniotic fluid and maternal serum.Methods The samples were collected from 23 pregnant women who were diagnosed as the full term IUGR, 42 normal full term pregnant women with normal infants’ weight were taken as control. Growth hormone and insulin were measured by radioimmunoassay. T3, T4 and TSH were investigated by micro-radioimmunoassay. Results The concentrations of growth hormone, insulin and T4 in umbilical cord blood were lower in IUGR than that in control group(GH4. 63μ/L vs 7. o1μg/L, insulin 1o. 68μIU/ml vs 31. 44μIU/ml, T487. 39nmol/L vs 138. 1onmol/L. P <o. o5, o. o5 and o. o5, respectively). The TSH concentration in umbilical cord blood was higher in IUGR than in control group (1o. 84μmIU/L vs 5. 75μmIU/L, P <o. o1 ). The concentration of growth hormone in maternal serum and the concentration of insulin in amniotic fluid were also lower in IUGR group than in control group(GH 1. 77μg/L vs 2. 74μg/L,P <o. o1, insulin 5. 84μIU/ml vs 15. 64μIU/ml, P <o. o1). Conclusion This study confirms that full term neonates with IUGR are abnormal in endocrine factors. The inadequacy of growth hormone may be one of the causes of IUGR. The relatlve scarcity of growth hormone and insulin seems to be a factor to compromise the fetus’ metabolism. Besides, the early hypothyrosis of infants with IUGR might protect them from unfavorable environment in the uterine.展开更多
In recent years,pollution caused by the discharge of industrial wastewater into Bohai Bay has posed a potential threat to the health of surrounding residents.Sludge was collected from the outlet of a factory that disc...In recent years,pollution caused by the discharge of industrial wastewater into Bohai Bay has posed a potential threat to the health of surrounding residents.Sludge was collected from the outlet of a factory that discharges effluent into Bohai Bay,and alcohol extracts of sludge(SE)were prepared.We confirmed by UPLC-MS/MS analysis that the SE contained PAHs,including fluorene,pyrene,and phenanthrene.Zebrafish embryos as animal models were exposed to 0.1,0.3,0.5,1 and 5 mg/mL SE from 2 to 4 h post-fertilization(hpf)until 120 hpf.The results showed that SE caused a concentration-dependent increase in mortality and a decrease in hatchability.We found that SE significantly reduced eye pigmentation and decreased the movement of embryos and larvae.In addition,SE decreased triiodothyronine(T3)content and down-regulated the mRNA expression of some thyroid hormone-related genes including TPO and Thrβ,and caused the up-regulation of Dio2 and Dio3 at 120 hpf.Exposure to three individual PAHs found in SE,namely fluorene,pyrene,and phenanthrene,caused morphological and transcriptional changes that were similar to those caused by SE exposure.These findings indicate that PAHs in SE can reduce the pigmentation of zebrafish,which may be related to the genetic changes associated with thyroid hormones,and that zebrafish eye pigmentation can be used as an indicator of PAHs exposure.展开更多
Background: Serum human chorionic gonadotrophin (hCG) is higher in twin than that in singleton pregnancies. As hCG stimulates the thyroid to produce more free thyroxine (FT4), which may lead to decreased thyroid-stimu...Background: Serum human chorionic gonadotrophin (hCG) is higher in twin than that in singleton pregnancies. As hCG stimulates the thyroid to produce more free thyroxine (FT4), which may lead to decreased thyroid-stimulating hormone (TSH) levels, the reference ranges of thyroid-related indicators may differ between singleton and twin pregnancies in the first trimester. This study aimed to establish reference ranges for thyroid-related indicators in early twin pregnancies and to compare them with singleton pregnancies. Methods: Data of 820 twin-pregnant women were extracted from the established database of all pregnant women who delivered at Peking University First Hospital from October 2013 to May 2018;160 who met National Academy of Clinical Biochemistry criteria were included to establish TSH and FT4 reference ranges. We screened 480 (3:1 paired) women with singleton pregnancies from the same database as controls. The Mann-Whitney test for TSH and FT4 levels was applied for comparisons between singleton and twin pregnancies. Results: First-trimester reference ranges (4–12 gestational weeks) for twin pregnancies were: TSH 0.69 (0.01–3.35) mIU/L and FT4 16.38 (12.45–23.34) pmol/L. Median TSH was significantly lower at 7 to 12 gestational weeks than that at 4 to 6 gestational weeks (0.62 vs. 0.96 mIU/L, Z =-1.964, P = 0.049);FT4 was not significantly different between the two groups. Compared to singleton pregnancies, median TSH was significantly lower (0.69 vs. 1.27 mIU/L, Z =-6.538, P = 0.000), and FT4 was significantly higher (16.38 vs. 14.85 pmol/L, Z =-7.399, P = 0.000) in twin pregnancies in the first trimester. Conclusions: Specific reference ranges for thyroid-related indicators for twin pregnancies are needed to avoid a misdiagnosis of thyroid dysfunction. Moreover, establishment of separate reference ranges for 4 to 6 and 7 to 12 gestational weeks in twin pregnancies may be considered.展开更多
Bisphenol A(BPA) is one of the highest volume industrial products worldwide and has been widely used to make various products as the intermediates of polycarbonate plastics and epoxy resins.Inevitably, general populat...Bisphenol A(BPA) is one of the highest volume industrial products worldwide and has been widely used to make various products as the intermediates of polycarbonate plastics and epoxy resins.Inevitably, general population has been widely exposed to BPA due to extensive use of BPAcontaining products. BPA has similar chemical structure with the natural estrogen and has been shown to induce a variety of estrogen-like endocrine effects on organism in vivo or in vitro. High doses of BPA tend to act as antagonist of estrogen receptors(ERs) by directly regulating the genomic transcription. However, BPA at environmentally relevant low-dose always disrupt the biological function via a non-genomic manner mediated by membrane receptors, rather than ERs. Although some studies had investigated the non-genomic effects of low-dose BPA, the exact molecular mechanism still remains unclear. Recently, we found that membrane G protein-coupled estrogen receptor 1 and integrin αvβ3 and its relative signal pathways participate in the induction of male germ cell proliferation and thyroid transcription disruption by the low-dose BPA. A profound understanding for the mechanism of action of the environmentally relevant BPA exposure not only contributes to objectively evaluate and predict the potential influence to human health, but also provides theoretical basis and methodological support for assessing health effects trigged by other estrogen-like environmental endocrine disruptors. Based mainly on our recent findings, this review outlines the research progress of molecular mechanism on endocrine disrupting effects of environmental low-dose BPA, existing problems and some consideration for future studies.展开更多
基金grants from the National Natural Science Foundation of China(No.81270885,No.81570726 and No.81600609)Shanghai Jiao Tong University School of Medicine(2014)+4 种基金the Ministry of Science and Technology in China(No.2012CB524906)the Science and Technology Commission of Shanghai Municipality(No.14495810700 and No.16410723200)Three-year Action Plan for Public Health System Construction in Shanghai by Shanghai Municipal Commission of Health and Family Planning(2015-2017)Clinical Potential Subject Construction of Shanghai Jiao Tong University School of Medicine(2014),Shanghai Municipal Health Bureau of China(No.20124262)Seed Founding of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine(No.JYZZ032).
文摘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.
文摘Objectives To evaluate the effect of thyroid hormone therapy with low dose of thyroxin on cardiac function in elderly patients with heart failure and sick euthyroid syndrome. Methods Forty-seven patients (33 males and 14 females, mean age 85.9+4.6 years,ranging from 80 to 99 years) with chronic heart failure (NYHA Ⅱ-Ⅳ) and low triiodothyronine (T3) state were randomly allocated to the treatment group or control group. The treatment group patients received oral administration of levothyroxine sodium (Euthyrox) 25-50mg/d in addition to conventional therapy of heart failure, whereas patients in control group were given conventional therapy only. Serum level of total T3 (TT3), free T3 (FT3), total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were determined. For both groups, left ventricular ejection fraction (LVEF) and stroke volume (SV) were assessed by two-dimensional echocardiography before and at 8 weeks after treatment. The changes of these parameters after the treatment were evaluated by adjusting heart rate in the two groups. Results The reduced serum T3 level in the treatment group was corrected after thyroid hormone therapy,and these patients had a significant improvement in cardiac function after treatment. By contrast, in the control group only changes of serum TT3 and TT4 levels and SV and LVEF after treatment were statistically significant. The heart rate-adjusted mean SV and LVEF in both groups were also increased, which was significantly greater in the treatment group than in the control group. Conclusion In the elderly patients with heart failure and sick euthyroid syndrome, addition of thyroxine at a low dosage to the conventional treatment could effectively improve the low T3 state and cardiac function independent of changes of heart rate.
文摘Introduction: Down syndrome (DS) is the most common chromosomal abnormality causing mental handicap in humans. Children with DS have significant medical problems and developmental delay which are further impaired by hypothyroidism. Those clinical features are potentially improved by using thyroxine replacement therapy. Objectives: To examine the evidence of effectiveness (motor & mental development) and safety of thyroxine supplementation in the treatment of SH and CH in children with DS. Methods: Several medical data bases (MEDLINE, EMBASE, CINAHL, Cochrane, Clinical Trials Gov, Essential Evidence and Google) were searched until 20 October, 2011, for randomized control trials (RCTs) that had examined thyroxine’s effectiveness and safety in the treatment of SH or CH in children with DS. Results: There were two high quality RCTs that examined thyroxine in the treatment of CH in children with DS, and no RCTs were found to have examined the effectiveness of thyroxine for SH in children with DS. Conclusion: The RCT which met our inclusion criteria provides the reliable evidence in recommending thyroxine for the treatment of CH in children with DS which is similar to the guidelines for general population. The absence of RCTs examining the treatment of SH in Children with DS indicates the need to conduct such trials.
文摘The present study deals with the effect of exogenous treatment of O. niloticus females with L-thyroxine (T4) on the development of the digestive system during larval rearing, and its subsequent effect on larval growth and survival. The development of the digestive tract and accessory glands was investigated histologically and histochemically in the developing O. niloticus larvae, from control and T4-treated spawners. During yolk-sac absorption, the digestive system of the fish underwent further differentiation and the rudimentary alimentary canal became segmented into four different histological regions: the buccopharynx, oesophagus, stomach and intestine. The injection of females O. niloticus with thyroxine (1 or 10 μg T4/g BW) greatly enhanced the development of the digestive tract and accessory glands of larvae as indicated by the quantitative and qualitative changes of the mucus composition from predominantly neutral to a mixture of neutral and acid mucosubstances, or acid mucosubstances occurred during the rearing period for the larvae produced from T4-treated females. This may be due to the direct effect of exogenous thyroxine, which might have been transferred from maternal circulation into the oocytes and larvae, on the synthesis of proteins, which increased with larval development. Thus, thyroxine directly or indirectly improved O. niloticus larval growth, since a marked increase in both, length and weight of larvae occurred during the experimental period. In addition, larvae from treated females also gave a significantly higher survival rate than that of control. It could be concluded that exogenous T4 in maternal circulation might have been transferred into oocytes and larvae. The transferred thyroid hormone appears to play some role in the early development of larvae and may confer a distinct advantage for the growth of the offspring of the Nile tilapia, O. niloticus.
文摘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.
文摘AIM: To investigate the impact of hypothyroidism and thyroxine therapy on insulin sensitivity in patients with overt hypothyroidism.METHODS: The study included twenty seven overtly hypothyroid and fifteen healthy euthyroid South Western Asian females.Both groups had matching age and body mass index.Physiological and pathological conditions as well as medications that may alter thyroid function,glucose homeostasis or serum lipids were ruled out.Serum thyrotropin(TSH),free tetraiodothyronine(FT4),free triiodothyronine(FT3),fasting insulin(FI),fasting plasma glucose(FPG),total cholesterol and triglycerides were measured before and six months after initiating thyroxine therapy for hypothyroid patients and once for the control group.Insulin resistance(IR) was estimated using homeostasis model assessment(HOMA-IR) and Body mass index(BMI) was calculated.RESULTS: Both study groups,hypothyroid patients and euthyroid control subjects,had matching age and body mass index(P-value 0.444,0.607 respectively).No significant difference was found between the hypothyroid patients and the euthyroid control group regarding fasting plasma glucose,fasting insulin,insulin resistance,total cholesterol and triglycerides(P-values 0.432,0.621,0.883,0.586,0.05 respectively).In the hypothyroid patients,triglycerides showed direct correlation to TSH and inverse correlation to FT3.Similarly total cholesterol inversely correlated to FT3 but its direct correlation to TSH did not reach statistical significance.After thyroxine replacement and reaching an euthyroid state as confirmed by clinical and laboratory data,there was no significant change in fasting plasma glucose,insulin resistance or triglyceride level(P-value 0.216,0.204,0.175 respectively) while total cholesterol significantly decreased(P-value 0.043) and fasting insulin significantly increased(P-value 0.047).CONCLUSION: Hypothyroidism has no impact on insulin sensitivity.Correction of hypothyroidism is not associated with a significant change of insulin sensitivity or triglycerides,but with a significant reduction of total cholesterol.
文摘Out of 100 cases of intractable schizophrenia,57 cases were in the group ofComputer-Controlled Electric Acupuncture (CCEA) and 43 in the control group.The therapeutic re-sults showed that clinically CCEA had a remarkably effective rate of 40. 35% on refractoryschizophrenia,which had much better curative effects than those in the control group.Through dy-namic evaluation of brief psychiatric rating scale (BPRS),negative symptom scale (SANS) and posi-tive symptom scale (SAPS) for both groups before,during and after treatment,the results indicatedthat in CCEA group the scores of BPRS,SANS and SAPS after treatment were much less than thosebefore treatment,which were remarkably different from those in the control group (P【0.01).Lab-oratory examination of thyroxin and androgen of patients in both groups before and after treatmentfound a significant result.
文摘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.
文摘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.
文摘The effects of khat on the hormonal levels have been established;however, the effects on human beings are controversial. The aim of our study was to investigate the possible effects of khat on the levels of serum thyroid hormones, testosterone, estradiol (E2), prolactin and cortisol in men. A total of 50 blood samples were collected from healthy males who referred to chew khat for more than 10 years and analyzed for the above hormones. The results were compared to the hormonal levels of 35 non khat chewers. Chewing khat causes significant increases in the testosterone (P < 0.03), prolactin (P < 0.05), E2 (P < 0.00005), FT3 (P < 0.04), and TSH (P < 0.05) levels. No significant differences were found in the serum level of FT4 between the two groups. The level of cortisol were significantly lower (P < 0.001) in the khat chewers group compared to the control group. This study suggests that khat chewing can cause reduction in the cortisol level, which may cause increases of testosterone, prolactin and E2. In addition, chewing khat increases the level of TSH and FT3 serum levels. Therefore, khat may contribute to the relevant disorders caused by abnormal levels of the studied hormones in the people who are chewing
基金Supported by Science and Technology Support Projects in Biomedicine Field of Shanghai Science and Technology Commission,No.19441907500Naval Medical University Military Medical Innovation,No.2017JS07Science and Technology Action Innovation Program by Science and Technology Commission of Shanghai,No.17411950104
文摘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.
文摘Vitamin D3 after its entrance in the organism undergoes hydroxylation on C-25 carbon atom by the action of microsomal liver enzymes giving the metabolite 25 hydroxyvitamin D3 (25OHD3). The function of microsomal liver enzymes is influenced in some specified states by hormones or drugs. It has approved that thyroxin is a potent stimulator of these enzymes while allopurinol suppresses their function. The aim of this issue is to examine 25OHD3 plasma levels in thyrotoxic subjects and in those pretreated with allopurinol on the base of the afford mentioned data. In a first phase 25OHD3 plasma levels were estimated in thyrotoxic subjects against euthytoid healthy controls. In a second phase lmg vitamin D3 was injected intravenously (i.v.) in thyrotoxic subjects and in healthy euthyroid controls. 25OHD3 plasma levels were measured before and in post injection period in six hours intervals for 48 hours. In a third phase a couple of subjects one thyrotoxic and one euthyroid healthy control pretreated both with allopurinol injected lmg of vitamin D3 i.v. In all studied subjects 25OHD3 plasma levels were measured before and in post injection period in six hours intervals for 48 hours. The pre and post injection 25OHD3 plasma levels measured the size of activity of liver enzyme responsible for bioactivation of vitamin D3. In the first phase was indicated that 25OHD3 plasma levels were lower in thyrotoxic subjects comparing with that of euthyroid healthy controls (p 3 in thyrotoxic subjects was 2,5 to 8 times faster comparing with euthyroid healthy controls. In the third phase was shown that allopurinol decreases the activity of liver enzymes function as regard the bioactivation of vitamin D3. The bioactivation of vitamin D3 is accelerated in thyrotoxicosis compared with that in euthyroid state. This phenomenon produces low 25OHD3 plasma levels in thyrotoxic subjects which initially may be normal or slightly increased depended from the vitamin D3 status in the thyrotoxic subjects. By continuous stimulatory action of increased thyroid hormones on liver enzymes the 25OHD3 plasma levels earlier or later decline in levels of hypo-or avitaminosis D3. The previously described biological events may explain the decreased intestinal calcium absorption of vitamin D3 and the osteomalacic component found in a percentage of thyrotoxic bone histology. For the blocking effects of allopurinol on liver enzymes function and possibly of other pharmaceutical products in relation to vitamin D3 bioactivation, available data are still lacking.
文摘Objective To investigate the relationship between intrauterine growth retardation (IUGR) and endocrine parameters so as to assess the effects or the main endocrine ractors on IUGR. The concentrations of growth hormone(GH), insulin, T3, T4 and TSH were measured in umbilical cord blood, amniotic fluid and maternal serum.Methods The samples were collected from 23 pregnant women who were diagnosed as the full term IUGR, 42 normal full term pregnant women with normal infants’ weight were taken as control. Growth hormone and insulin were measured by radioimmunoassay. T3, T4 and TSH were investigated by micro-radioimmunoassay. Results The concentrations of growth hormone, insulin and T4 in umbilical cord blood were lower in IUGR than that in control group(GH4. 63μ/L vs 7. o1μg/L, insulin 1o. 68μIU/ml vs 31. 44μIU/ml, T487. 39nmol/L vs 138. 1onmol/L. P <o. o5, o. o5 and o. o5, respectively). The TSH concentration in umbilical cord blood was higher in IUGR than in control group (1o. 84μmIU/L vs 5. 75μmIU/L, P <o. o1 ). The concentration of growth hormone in maternal serum and the concentration of insulin in amniotic fluid were also lower in IUGR group than in control group(GH 1. 77μg/L vs 2. 74μg/L,P <o. o1, insulin 5. 84μIU/ml vs 15. 64μIU/ml, P <o. o1). Conclusion This study confirms that full term neonates with IUGR are abnormal in endocrine factors. The inadequacy of growth hormone may be one of the causes of IUGR. The relatlve scarcity of growth hormone and insulin seems to be a factor to compromise the fetus’ metabolism. Besides, the early hypothyrosis of infants with IUGR might protect them from unfavorable environment in the uterine.
基金funded by the National Natural Science Foundation of China(82060672)the Program for Interdisciplinary Innovation team in Inner Mongolia Minzu University,China(Dongwu-2023)the Natural Science Foundation of Inner Mongolia Autonomous Region of China(2020MS08103).
文摘In recent years,pollution caused by the discharge of industrial wastewater into Bohai Bay has posed a potential threat to the health of surrounding residents.Sludge was collected from the outlet of a factory that discharges effluent into Bohai Bay,and alcohol extracts of sludge(SE)were prepared.We confirmed by UPLC-MS/MS analysis that the SE contained PAHs,including fluorene,pyrene,and phenanthrene.Zebrafish embryos as animal models were exposed to 0.1,0.3,0.5,1 and 5 mg/mL SE from 2 to 4 h post-fertilization(hpf)until 120 hpf.The results showed that SE caused a concentration-dependent increase in mortality and a decrease in hatchability.We found that SE significantly reduced eye pigmentation and decreased the movement of embryos and larvae.In addition,SE decreased triiodothyronine(T3)content and down-regulated the mRNA expression of some thyroid hormone-related genes including TPO and Thrβ,and caused the up-regulation of Dio2 and Dio3 at 120 hpf.Exposure to three individual PAHs found in SE,namely fluorene,pyrene,and phenanthrene,caused morphological and transcriptional changes that were similar to those caused by SE exposure.These findings indicate that PAHs in SE can reduce the pigmentation of zebrafish,which may be related to the genetic changes associated with thyroid hormones,and that zebrafish eye pigmentation can be used as an indicator of PAHs exposure.
文摘Background: Serum human chorionic gonadotrophin (hCG) is higher in twin than that in singleton pregnancies. As hCG stimulates the thyroid to produce more free thyroxine (FT4), which may lead to decreased thyroid-stimulating hormone (TSH) levels, the reference ranges of thyroid-related indicators may differ between singleton and twin pregnancies in the first trimester. This study aimed to establish reference ranges for thyroid-related indicators in early twin pregnancies and to compare them with singleton pregnancies. Methods: Data of 820 twin-pregnant women were extracted from the established database of all pregnant women who delivered at Peking University First Hospital from October 2013 to May 2018;160 who met National Academy of Clinical Biochemistry criteria were included to establish TSH and FT4 reference ranges. We screened 480 (3:1 paired) women with singleton pregnancies from the same database as controls. The Mann-Whitney test for TSH and FT4 levels was applied for comparisons between singleton and twin pregnancies. Results: First-trimester reference ranges (4–12 gestational weeks) for twin pregnancies were: TSH 0.69 (0.01–3.35) mIU/L and FT4 16.38 (12.45–23.34) pmol/L. Median TSH was significantly lower at 7 to 12 gestational weeks than that at 4 to 6 gestational weeks (0.62 vs. 0.96 mIU/L, Z =-1.964, P = 0.049);FT4 was not significantly different between the two groups. Compared to singleton pregnancies, median TSH was significantly lower (0.69 vs. 1.27 mIU/L, Z =-6.538, P = 0.000), and FT4 was significantly higher (16.38 vs. 14.85 pmol/L, Z =-7.399, P = 0.000) in twin pregnancies in the first trimester. Conclusions: Specific reference ranges for thyroid-related indicators for twin pregnancies are needed to avoid a misdiagnosis of thyroid dysfunction. Moreover, establishment of separate reference ranges for 4 to 6 and 7 to 12 gestational weeks in twin pregnancies may be considered.
基金supported by Strategic Priority Research Program of the Chinese Academy of Sciences (No.XDB01020300)the National Natural Science Foundation of China (Nos.21377158,21577149,21477139,21237005,21621064 and 21321004)
文摘Bisphenol A(BPA) is one of the highest volume industrial products worldwide and has been widely used to make various products as the intermediates of polycarbonate plastics and epoxy resins.Inevitably, general population has been widely exposed to BPA due to extensive use of BPAcontaining products. BPA has similar chemical structure with the natural estrogen and has been shown to induce a variety of estrogen-like endocrine effects on organism in vivo or in vitro. High doses of BPA tend to act as antagonist of estrogen receptors(ERs) by directly regulating the genomic transcription. However, BPA at environmentally relevant low-dose always disrupt the biological function via a non-genomic manner mediated by membrane receptors, rather than ERs. Although some studies had investigated the non-genomic effects of low-dose BPA, the exact molecular mechanism still remains unclear. Recently, we found that membrane G protein-coupled estrogen receptor 1 and integrin αvβ3 and its relative signal pathways participate in the induction of male germ cell proliferation and thyroid transcription disruption by the low-dose BPA. A profound understanding for the mechanism of action of the environmentally relevant BPA exposure not only contributes to objectively evaluate and predict the potential influence to human health, but also provides theoretical basis and methodological support for assessing health effects trigged by other estrogen-like environmental endocrine disruptors. Based mainly on our recent findings, this review outlines the research progress of molecular mechanism on endocrine disrupting effects of environmental low-dose BPA, existing problems and some consideration for future studies.
