Transactivation of thyroid hormone receptor βΔ on target genes through thyroid hormone responsive element

研究TRβΔ是否具有转录因子活性.将pcDNA3.1-TRβΔ和荧光素酶报告基因pGL3-Promoter/甲状腺激素反应元件共转染COS-7,检测报告基因表达水平.结果 显示报告基因表达水平可被T3提高45倍.证实TRβΔ是一个受配体(T3)诱导的转录因子.     

甲状腺激素调节靶基因转录的分子机制

甲状腺激素受体(TR)为配体依赖性转录因子.未结合T3的TR与辅阻遏因子等形成复合物,此复合物通过使局部的组蛋白去乙酰化而使局部染色质变得紧密,进而抑制靶基因的基础转录.结合了T3的TR与辅阻遏因子解离,转录恢复到基础水平.随后辅激活因子与结合了T3的TR形成复合物,此复合物通过使组蛋白乙酰化而使局部染色质变得松弛,进而激活靶基因的转录.辅激活因子复合物还能使RNA聚合酶稳定,从而促进转录.     

甲状腺激素调节靶基因转录的分子机制

甲状腺激素受体（TR）为配体依赖性转录因子。未结合T3的TR与辅阻遏因子等形成复合物，此复合物通过使局部的组蛋白去乙酰化而使局部染色质变得紧密，进而抑制靶基因的基础转录，结合了T3的TR与辅阻遏因子解离，转录恢复到基础水平，随后辅激活因子与结合了T3的TR形成复合物，此复合物通过使组蛋白乙酰化而使局部染色质变得松弛，进而激活靶基因的转录。辅激活因子复合物还能使RNA聚合酶稳定，从而促进转录。     

c-Jun氨基末端激酶信号转导途径与胰岛β细胞凋亡

甲状腺激素受体 (TR)为配体依赖性转录因子。未结合T3 的TR与辅阻遏因子等形成复合物 ,此复合物通过使局部的组蛋白去乙酰化而使局部染色质变得紧密 ,进而抑制靶基因的基础转录。结合了T3 的TR与辅阻遏因子解离 ,转录恢复到基础水平。随后辅激活因子与结合了T3 的TR形成复合物 ,此复合物通过使组蛋白乙酰化而使局部染色质变得松弛 ,进而激活靶基因的转录。辅激活因子复合物还能使RNA聚合酶稳定 ,从而促进转录     

甲状腺激素对成骨样MG-63细胞甲状腺激素受体不同亚型表达的影响

目的 检测人类成骨样细胞MG-63中甲状腺激素受体(TR)的表达情况以及甲状腺激素(T3或T4)对其的影响.方法 用实时荧光定量PCR法对MG-63细胞中TR的主要4个亚型,α1、α1、β1、β2的mRNA表达进行了测定.结果 TRα1 mRNA的表达水平最高,为10.70±0.45;TRβ1仅及其半,为5.75±0.10;TRβ2不低,相当于TRβ1的60%,为3.34±0.08;TRα2的表达极低,仅为(3.66±0.59)×10-2.分别加入不同浓度的T3或T4,仅TRα1和TRα2对T3表现明显的降调节,且TRα1和TRα2的表达与相应T3浓度之间负相关,其他亚型无显著性变化,也无相关关系;同样浓度范围的T4作用各亚型,表达均无显著性变化.结论 在骨细胞发育分化中TRα1起关键作用.

Abstract：

Objective To examine the expression of thyroid hormone receptor isoforms (TR α1, α2, β1, and β2) in human osteoblast-like cell line MG-63 at the mRNA level and the effect of thyroid hormone (T3 or T4 ) on the expression. Methods Realtime quantitative PCR was performed. Results The expression of TRα1 mRNA was the highest, that was 10. 70± 0.45, TRβ1 was 5.75 ± 0. 10, TRβ2 was 3.34 ± 0. 08, and TRα2 was very low, only (3.66 ±0. 59) × 10-2. Only the expression of TRαl and TRα2 mRNA was down regulated significantly by the treatment of 10-10 ～ 10-6 mol/L T3, and there was a negative correlation between the expression of TRα1 or TRα2 mRNA and the concentration of T3. Conclusion TRα1 plays a primary role in mediating the effects of thyroid hormones in skeletal development.     

甲状腺激素受体研究进展

甲状腺激素受体（TR）为核受体超家族的成员，其分子中含有A-F6个区，组成3个功能域，TR有若干异形体，其中TRα1,TRβ1和TRβ2可结合T3。为功能性受体。一些甲状腺激素拟似剂虽能与TR结合但不能激活TR，可作为TR的拮抗剂，大多数TRα和（或）TRβ基因剔除的小鼠都可存活，其表型甚至接近野生型。     

甲状腺激素受体研究进展

甲状腺激素受体 (TR)为核受体超家族的成员 ,其分子中含有A～F 6个区 ,组成 3个功能域。TR有若干异形体 ,其中TRα1、TRβ1和TRβ2可结合T3 ,为功能性受体。一些甲状腺激素拟似剂虽能与TR结合但不能激活TR ,可作为TR的拮抗剂。大多数TRα和 (或 )TRβ基因剔除的小鼠都可存活 ,其表型甚至接近野生型。     

T3对人神经干细胞分化过程中甲状腺激素受体表达的影响

目的探讨三碘甲状腺原氨酸(triiodothyronine,T3)在人神经干细胞分化中的作用以及甲状腺激素受体(thyroid hormone receptors,TRs)mRNA在神经干细胞(neural stem cell,NSC)分化过程中的表达变化.方法在体外成功诱导扩增NSC,用T3对NSC进行诱导分化,RT-PCR半定量法检测NSC在分化前后TR mRNA的表达变化,免疫细胞化学方法鉴定分化后的细胞类型.结果 T3可诱导NSC分化为神经元、少突和星形胶质细胞,其中髓鞘碱性蛋白(MBP)阳性细胞约占80%,同时自身受体表达在经历时空性变化后一致下调,表达水平均低于干细胞状态.结论 T3能诱导NSC向胶质细胞分化,是少突胶质细胞分化的重要调控因子,并通过TR的时空表达来发挥其重要生理作用.     

人甲状腺激素受体相互作用蛋白15与甲状腺激素受体的相互作用

目的　确立人甲状腺激素受体相互作用蛋白 15 (hTRIP15 )与甲状腺激素受体 (TR)的相互作用及其作用方式。方法　应用酵母双杂交技术及半乳糖苷酶定性或定量测定。结果　将构建质粒 (BD TRIP15与AD TR)共转化AH10 9酵母细胞后 ,在高严格度选择的培养基 (SD Leu Trp Ade His) 10天克隆长出 ,相比阳性对照质粒 (BD P5 3 +AD Tag)共转后 3天克隆生长。将构建载体及对照载体转化Y187酵母菌株 ,检测LacZ报告基因的表达 (β gal单位 ) ,阳性对照质粒 (BD P5 3 +AD Tag)为 14 9.5 7± 0 .5 1,BD TRIP15 +AD TR为 3 .2 3± 10 .15 ,加入T3 后为 2 .0 2± 0 .0 8,而阴性对照质粒 (BD P5 3 +AD LamC)仅为 0 .0 2± 0 .0 1β gal单位 ,且T3 呈剂量依赖方式抑制两者的相互作用。结论　hTPIR15能与TR共相互作用 ,T3 呈剂量依赖方式抑制两者间的作用 ,仅在超大剂量时才可完全阻断hTRIP15与TRα间的作用。     

TRβ基因突变致甲状腺激素抵抗综合征

目的 研究一甲状腺激素抵抗综合征家系的甲状腺激素受体β( thyroid hormone reecptorβ)的基因突变情况.方法 提取患者及其家系5名成员的外周血基因组DNA,PGR分段扩增TRβ基因1-10号外显子,产物直接进行DNA测序检测突变位点.结果 测序结果显示,该家系中有2名成员TRβ基因第10外显子1642位核苷酸发生C转换为A的错义突变,使该位点所编码的氨基酸由脯氨酸变为苏氨酸(P453T),此种突变为杂合子突变.结论 经基因测序检测诊断证实患者TRβ基因第10外显子存在P453T突变,该突变可能导致了甲状腺激素抵抗综合征发生.     

Effect of thyroid hormone level on the expression of synaptotagmin Ⅰ in adult rat hippocampus

Objective To observe the effect of different thyroid hormone level on the expression of synaptotagmin Ⅰ(Syt Ⅰ) in adult rat hippocampus. Methods All 28 adult male SD rats were assigned randomly into hypothyroid, hyperthyroid and control group, hypothyroid group was established by daily intraperitoneal injections with propylthiou raci(PTU, 10.0 mg/kg body weight) for 6 weeks and hyperthyroid group with L-Thyroxine (L-T4, 0.5 mg/kg body weight) for 3 weeks. Radioimmunity method was used to assay the levels of serum T3 and T4, immunohistochemical S-P technology to assay the levels of Syt Ⅰ protein in hippoeampus CA1, CA3 and dentate gyrus (DG). The layers analyzed in the different subfields include the polymorphic cell layer(the stratum oriens, SO), pyramidal cell layer(PCL), stratum radiatum (SR), lacunosum-molecular layer (SLM) in CA1 and CA3, granular cell layer(GL) and molecular layer(ML) in DG. Results The levels of serum T3 and T4[(0.34±0.12), (41.03± 11.37)nmol/L]in the hypothyroid rats were significantly lower than those in the control group[(0.65±0.15), (55.20±10.68)nmol/L, P < 0.01 or < 0.05], and the positive granule of Syt Ⅰ was significantly lower in PCL and SR of CA1 and CA3, GL of DG. The average optical value responsible for Syt Ⅰ immunoreactivity was obviously reduced in SO(0.048±0.007), PCL(0.299±0.035), SR(0.042±0.007), SLM(0.038±0.006) of CA1, PCL(0.085± 0.019), SR(0.040±0.011), SLM (0.038±0.006) of CA3, GL (0.076±0.019) of DG than normal controls (0.068± 0.014, 0.376±0.053, 0.053±0.008,0.056±0.009,0.118±0.026,0.052±0.010,0.053±0.009,0.099±0.015; P< 0.01 or < 0.05). Serum T3 and T4 levels [(1.43±0.30), (157.18±19.95)nmol/L]of hyperthyroid rats were significantly higher than those of control group(P < 0.01). The value was reduced in PCL(0.322±0.050), SR(0.039±0.006), SLM (0.042±0.006) of CA1, PCL(0.098±0.034), SR(0.046±0.013), SLM(0.046±0.010) of CA3 and GL(0.085± 0.024), ML (0.042±0.009) of DG (P < 0.05 or < 0.01). Conclusion Adult-onset of hypothyroidism and hyperthyroidism can reversibly decrease the expression of Syt Ⅰ in CA1, CA3 and DG regions of hippocampus.     

Effect of thyroid hormone level on the expression of synaptotagmin Ⅰ in adult rat hippocampus

Objective To observe the effect of different thyroid hormone level on the expression of synaptotagmin Ⅰ(Syt Ⅰ) in adult rat hippocampus. Methods All 28 adult male SD rats were assigned randomly into hypothyroid, hyperthyroid and control group, hypothyroid group was established by daily intraperitoneal injections with propylthiou raci(PTU, 10.0 mg/kg body weight) for 6 weeks and hyperthyroid group with L-Thyroxine (L-T4, 0.5 mg/kg body weight) for 3 weeks. Radioimmunity method was used to assay the levels of serum T3 and T4, immunohistochemical S-P technology to assay the levels of Syt Ⅰ protein in hippoeampus CA1, CA3 and dentate gyrus (DG). The layers analyzed in the different subfields include the polymorphic cell layer(the stratum oriens, SO), pyramidal cell layer(PCL), stratum radiatum (SR), lacunosum-molecular layer (SLM) in CA1 and CA3, granular cell layer(GL) and molecular layer(ML) in DG. Results The levels of serum T3 and T4[(0.34±0.12), (41.03± 11.37)nmol/L]in the hypothyroid rats were significantly lower than those in the control group[(0.65±0.15), (55.20±10.68)nmol/L, P < 0.01 or < 0.05], and the positive granule of Syt Ⅰ was significantly lower in PCL and SR of CA1 and CA3, GL of DG. The average optical value responsible for Syt Ⅰ immunoreactivity was obviously reduced in SO(0.048±0.007), PCL(0.299±0.035), SR(0.042±0.007), SLM(0.038±0.006) of CA1, PCL(0.085± 0.019), SR(0.040±0.011), SLM (0.038±0.006) of CA3, GL (0.076±0.019) of DG than normal controls (0.068± 0.014, 0.376±0.053, 0.053±0.008,0.056±0.009,0.118±0.026,0.052±0.010,0.053±0.009,0.099±0.015; P< 0.01 or < 0.05). Serum T3 and T4 levels [(1.43±0.30), (157.18±19.95)nmol/L]of hyperthyroid rats were significantly higher than those of control group(P < 0.01). The value was reduced in PCL(0.322±0.050), SR(0.039±0.006), SLM (0.042±0.006) of CA1, PCL(0.098±0.034), SR(0.046±0.013), SLM(0.046±0.010) of CA3 and GL(0.085± 0.024), ML (0.042±0.009) of DG (P < 0.05 or < 0.01). Conclusion Adult-onset of hypothyroidism and hyperthyroidism can reversibly decrease the expression of Syt Ⅰ in CA1, CA3 and DG regions of hippocampus.     

Effect of thyroid hormone level on the expression of synaptotagmin Ⅰ in adult rat hippocampus

Objective To observe the effect of different thyroid hormone level on the expression of synaptotagmin Ⅰ(Syt Ⅰ) in adult rat hippocampus. Methods All 28 adult male SD rats were assigned randomly into hypothyroid, hyperthyroid and control group, hypothyroid group was established by daily intraperitoneal injections with propylthiou raci(PTU, 10.0 mg/kg body weight) for 6 weeks and hyperthyroid group with L-Thyroxine (L-T4, 0.5 mg/kg body weight) for 3 weeks. Radioimmunity method was used to assay the levels of serum T3 and T4, immunohistochemical S-P technology to assay the levels of Syt Ⅰ protein in hippoeampus CA1, CA3 and dentate gyrus (DG). The layers analyzed in the different subfields include the polymorphic cell layer(the stratum oriens, SO), pyramidal cell layer(PCL), stratum radiatum (SR), lacunosum-molecular layer (SLM) in CA1 and CA3, granular cell layer(GL) and molecular layer(ML) in DG. Results The levels of serum T3 and T4[(0.34±0.12), (41.03± 11.37)nmol/L]in the hypothyroid rats were significantly lower than those in the control group[(0.65±0.15), (55.20±10.68)nmol/L, P < 0.01 or < 0.05], and the positive granule of Syt Ⅰ was significantly lower in PCL and SR of CA1 and CA3, GL of DG. The average optical value responsible for Syt Ⅰ immunoreactivity was obviously reduced in SO(0.048±0.007), PCL(0.299±0.035), SR(0.042±0.007), SLM(0.038±0.006) of CA1, PCL(0.085± 0.019), SR(0.040±0.011), SLM (0.038±0.006) of CA3, GL (0.076±0.019) of DG than normal controls (0.068± 0.014, 0.376±0.053, 0.053±0.008,0.056±0.009,0.118±0.026,0.052±0.010,0.053±0.009,0.099±0.015; P< 0.01 or < 0.05). Serum T3 and T4 levels [(1.43±0.30), (157.18±19.95)nmol/L]of hyperthyroid rats were significantly higher than those of control group(P < 0.01). The value was reduced in PCL(0.322±0.050), SR(0.039±0.006), SLM (0.042±0.006) of CA1, PCL(0.098±0.034), SR(0.046±0.013), SLM(0.046±0.010) of CA3 and GL(0.085± 0.024), ML (0.042±0.009) of DG (P < 0.05 or < 0.01). Conclusion Adult-onset of hypothyroidism and hyperthyroidism can reversibly decrease the expression of Syt Ⅰ in CA1, CA3 and DG regions of hippocampus.     

Effect of thyroid hormone level on the expression of synaptotagmin Ⅰ in adult rat hippocampus

Objective To observe the effect of different thyroid hormone level on the expression of synaptotagmin Ⅰ(Syt Ⅰ) in adult rat hippocampus. Methods All 28 adult male SD rats were assigned randomly into hypothyroid, hyperthyroid and control group, hypothyroid group was established by daily intraperitoneal injections with propylthiou raci(PTU, 10.0 mg/kg body weight) for 6 weeks and hyperthyroid group with L-Thyroxine (L-T4, 0.5 mg/kg body weight) for 3 weeks. Radioimmunity method was used to assay the levels of serum T3 and T4, immunohistochemical S-P technology to assay the levels of Syt Ⅰ protein in hippoeampus CA1, CA3 and dentate gyrus (DG). The layers analyzed in the different subfields include the polymorphic cell layer(the stratum oriens, SO), pyramidal cell layer(PCL), stratum radiatum (SR), lacunosum-molecular layer (SLM) in CA1 and CA3, granular cell layer(GL) and molecular layer(ML) in DG. Results The levels of serum T3 and T4[(0.34±0.12), (41.03± 11.37)nmol/L]in the hypothyroid rats were significantly lower than those in the control group[(0.65±0.15), (55.20±10.68)nmol/L, P < 0.01 or < 0.05], and the positive granule of Syt Ⅰ was significantly lower in PCL and SR of CA1 and CA3, GL of DG. The average optical value responsible for Syt Ⅰ immunoreactivity was obviously reduced in SO(0.048±0.007), PCL(0.299±0.035), SR(0.042±0.007), SLM(0.038±0.006) of CA1, PCL(0.085± 0.019), SR(0.040±0.011), SLM (0.038±0.006) of CA3, GL (0.076±0.019) of DG than normal controls (0.068± 0.014, 0.376±0.053, 0.053±0.008,0.056±0.009,0.118±0.026,0.052±0.010,0.053±0.009,0.099±0.015; P< 0.01 or < 0.05). Serum T3 and T4 levels [(1.43±0.30), (157.18±19.95)nmol/L]of hyperthyroid rats were significantly higher than those of control group(P < 0.01). The value was reduced in PCL(0.322±0.050), SR(0.039±0.006), SLM (0.042±0.006) of CA1, PCL(0.098±0.034), SR(0.046±0.013), SLM(0.046±0.010) of CA3 and GL(0.085± 0.024), ML (0.042±0.009) of DG (P < 0.05 or < 0.01). Conclusion Adult-onset of hypothyroidism and hyperthyroidism can reversibly decrease the expression of Syt Ⅰ in CA1, CA3 and DG regions of hippocampus.     

Effect of thyroid hormone level on the expression of synaptotagmin Ⅰ in adult rat hippocampus

Objective To observe the effect of different thyroid hormone level on the expression of synaptotagmin Ⅰ(Syt Ⅰ) in adult rat hippocampus. Methods All 28 adult male SD rats were assigned randomly into hypothyroid, hyperthyroid and control group, hypothyroid group was established by daily intraperitoneal injections with propylthiou raci(PTU, 10.0 mg/kg body weight) for 6 weeks and hyperthyroid group with L-Thyroxine (L-T4, 0.5 mg/kg body weight) for 3 weeks. Radioimmunity method was used to assay the levels of serum T3 and T4, immunohistochemical S-P technology to assay the levels of Syt Ⅰ protein in hippoeampus CA1, CA3 and dentate gyrus (DG). The layers analyzed in the different subfields include the polymorphic cell layer(the stratum oriens, SO), pyramidal cell layer(PCL), stratum radiatum (SR), lacunosum-molecular layer (SLM) in CA1 and CA3, granular cell layer(GL) and molecular layer(ML) in DG. Results The levels of serum T3 and T4[(0.34±0.12), (41.03± 11.37)nmol/L]in the hypothyroid rats were significantly lower than those in the control group[(0.65±0.15), (55.20±10.68)nmol/L, P < 0.01 or < 0.05], and the positive granule of Syt Ⅰ was significantly lower in PCL and SR of CA1 and CA3, GL of DG. The average optical value responsible for Syt Ⅰ immunoreactivity was obviously reduced in SO(0.048±0.007), PCL(0.299±0.035), SR(0.042±0.007), SLM(0.038±0.006) of CA1, PCL(0.085± 0.019), SR(0.040±0.011), SLM (0.038±0.006) of CA3, GL (0.076±0.019) of DG than normal controls (0.068± 0.014, 0.376±0.053, 0.053±0.008,0.056±0.009,0.118±0.026,0.052±0.010,0.053±0.009,0.099±0.015; P< 0.01 or < 0.05). Serum T3 and T4 levels [(1.43±0.30), (157.18±19.95)nmol/L]of hyperthyroid rats were significantly higher than those of control group(P < 0.01). The value was reduced in PCL(0.322±0.050), SR(0.039±0.006), SLM (0.042±0.006) of CA1, PCL(0.098±0.034), SR(0.046±0.013), SLM(0.046±0.010) of CA3 and GL(0.085± 0.024), ML (0.042±0.009) of DG (P < 0.05 or < 0.01). Conclusion Adult-onset of hypothyroidism and hyperthyroidism can reversibly decrease the expression of Syt Ⅰ in CA1, CA3 and DG regions of hippocampus.     

Effect of thyroid hormone level on the expression of synaptotagmin Ⅰ in adult rat hippocampus

Objective To observe the effect of different thyroid hormone level on the expression of synaptotagmin Ⅰ(Syt Ⅰ) in adult rat hippocampus. Methods All 28 adult male SD rats were assigned randomly into hypothyroid, hyperthyroid and control group, hypothyroid group was established by daily intraperitoneal injections with propylthiou raci(PTU, 10.0 mg/kg body weight) for 6 weeks and hyperthyroid group with L-Thyroxine (L-T4, 0.5 mg/kg body weight) for 3 weeks. Radioimmunity method was used to assay the levels of serum T3 and T4, immunohistochemical S-P technology to assay the levels of Syt Ⅰ protein in hippoeampus CA1, CA3 and dentate gyrus (DG). The layers analyzed in the different subfields include the polymorphic cell layer(the stratum oriens, SO), pyramidal cell layer(PCL), stratum radiatum (SR), lacunosum-molecular layer (SLM) in CA1 and CA3, granular cell layer(GL) and molecular layer(ML) in DG. Results The levels of serum T3 and T4[(0.34±0.12), (41.03± 11.37)nmol/L]in the hypothyroid rats were significantly lower than those in the control group[(0.65±0.15), (55.20±10.68)nmol/L, P < 0.01 or < 0.05], and the positive granule of Syt Ⅰ was significantly lower in PCL and SR of CA1 and CA3, GL of DG. The average optical value responsible for Syt Ⅰ immunoreactivity was obviously reduced in SO(0.048±0.007), PCL(0.299±0.035), SR(0.042±0.007), SLM(0.038±0.006) of CA1, PCL(0.085± 0.019), SR(0.040±0.011), SLM (0.038±0.006) of CA3, GL (0.076±0.019) of DG than normal controls (0.068± 0.014, 0.376±0.053, 0.053±0.008,0.056±0.009,0.118±0.026,0.052±0.010,0.053±0.009,0.099±0.015; P< 0.01 or < 0.05). Serum T3 and T4 levels [(1.43±0.30), (157.18±19.95)nmol/L]of hyperthyroid rats were significantly higher than those of control group(P < 0.01). The value was reduced in PCL(0.322±0.050), SR(0.039±0.006), SLM (0.042±0.006) of CA1, PCL(0.098±0.034), SR(0.046±0.013), SLM(0.046±0.010) of CA3 and GL(0.085± 0.024), ML (0.042±0.009) of DG (P < 0.05 or < 0.01). Conclusion Adult-onset of hypothyroidism and hyperthyroidism can reversibly decrease the expression of Syt Ⅰ in CA1, CA3 and DG regions of hippocampus.     

Effect of thyroid hormone level on the expression of synaptotagmin Ⅰ in adult rat hippocampus

Objective To observe the effect of different thyroid hormone level on the expression of synaptotagmin Ⅰ(Syt Ⅰ) in adult rat hippocampus. Methods All 28 adult male SD rats were assigned randomly into hypothyroid, hyperthyroid and control group, hypothyroid group was established by daily intraperitoneal injections with propylthiou raci(PTU, 10.0 mg/kg body weight) for 6 weeks and hyperthyroid group with L-Thyroxine (L-T4, 0.5 mg/kg body weight) for 3 weeks. Radioimmunity method was used to assay the levels of serum T3 and T4, immunohistochemical S-P technology to assay the levels of Syt Ⅰ protein in hippoeampus CA1, CA3 and dentate gyrus (DG). The layers analyzed in the different subfields include the polymorphic cell layer(the stratum oriens, SO), pyramidal cell layer(PCL), stratum radiatum (SR), lacunosum-molecular layer (SLM) in CA1 and CA3, granular cell layer(GL) and molecular layer(ML) in DG. Results The levels of serum T3 and T4[(0.34±0.12), (41.03± 11.37)nmol/L]in the hypothyroid rats were significantly lower than those in the control group[(0.65±0.15), (55.20±10.68)nmol/L, P < 0.01 or < 0.05], and the positive granule of Syt Ⅰ was significantly lower in PCL and SR of CA1 and CA3, GL of DG. The average optical value responsible for Syt Ⅰ immunoreactivity was obviously reduced in SO(0.048±0.007), PCL(0.299±0.035), SR(0.042±0.007), SLM(0.038±0.006) of CA1, PCL(0.085± 0.019), SR(0.040±0.011), SLM (0.038±0.006) of CA3, GL (0.076±0.019) of DG than normal controls (0.068± 0.014, 0.376±0.053, 0.053±0.008,0.056±0.009,0.118±0.026,0.052±0.010,0.053±0.009,0.099±0.015; P< 0.01 or < 0.05). Serum T3 and T4 levels [(1.43±0.30), (157.18±19.95)nmol/L]of hyperthyroid rats were significantly higher than those of control group(P < 0.01). The value was reduced in PCL(0.322±0.050), SR(0.039±0.006), SLM (0.042±0.006) of CA1, PCL(0.098±0.034), SR(0.046±0.013), SLM(0.046±0.010) of CA3 and GL(0.085± 0.024), ML (0.042±0.009) of DG (P < 0.05 or < 0.01). Conclusion Adult-onset of hypothyroidism and hyperthyroidism can reversibly decrease the expression of Syt Ⅰ in CA1, CA3 and DG regions of hippocampus.     

Effect of thyroid hormone level on the expression of synaptotagmin Ⅰ in adult rat hippocampus

Objective To observe the effect of different thyroid hormone level on the expression of synaptotagmin Ⅰ(Syt Ⅰ) in adult rat hippocampus. Methods All 28 adult male SD rats were assigned randomly into hypothyroid, hyperthyroid and control group, hypothyroid group was established by daily intraperitoneal injections with propylthiou raci(PTU, 10.0 mg/kg body weight) for 6 weeks and hyperthyroid group with L-Thyroxine (L-T4, 0.5 mg/kg body weight) for 3 weeks. Radioimmunity method was used to assay the levels of serum T3 and T4, immunohistochemical S-P technology to assay the levels of Syt Ⅰ protein in hippoeampus CA1, CA3 and dentate gyrus (DG). The layers analyzed in the different subfields include the polymorphic cell layer(the stratum oriens, SO), pyramidal cell layer(PCL), stratum radiatum (SR), lacunosum-molecular layer (SLM) in CA1 and CA3, granular cell layer(GL) and molecular layer(ML) in DG. Results The levels of serum T3 and T4[(0.34±0.12), (41.03± 11.37)nmol/L]in the hypothyroid rats were significantly lower than those in the control group[(0.65±0.15), (55.20±10.68)nmol/L, P < 0.01 or < 0.05], and the positive granule of Syt Ⅰ was significantly lower in PCL and SR of CA1 and CA3, GL of DG. The average optical value responsible for Syt Ⅰ immunoreactivity was obviously reduced in SO(0.048±0.007), PCL(0.299±0.035), SR(0.042±0.007), SLM(0.038±0.006) of CA1, PCL(0.085± 0.019), SR(0.040±0.011), SLM (0.038±0.006) of CA3, GL (0.076±0.019) of DG than normal controls (0.068± 0.014, 0.376±0.053, 0.053±0.008,0.056±0.009,0.118±0.026,0.052±0.010,0.053±0.009,0.099±0.015; P< 0.01 or < 0.05). Serum T3 and T4 levels [(1.43±0.30), (157.18±19.95)nmol/L]of hyperthyroid rats were significantly higher than those of control group(P < 0.01). The value was reduced in PCL(0.322±0.050), SR(0.039±0.006), SLM (0.042±0.006) of CA1, PCL(0.098±0.034), SR(0.046±0.013), SLM(0.046±0.010) of CA3 and GL(0.085± 0.024), ML (0.042±0.009) of DG (P < 0.05 or < 0.01). Conclusion Adult-onset of hypothyroidism and hyperthyroidism can reversibly decrease the expression of Syt Ⅰ in CA1, CA3 and DG regions of hippocampus.     

Effect of thyroid hormone level on the expression of synaptotagmin Ⅰ in adult rat hippocampus

Objective To observe the effect of different thyroid hormone level on the expression of synaptotagmin Ⅰ(Syt Ⅰ) in adult rat hippocampus. Methods All 28 adult male SD rats were assigned randomly into hypothyroid, hyperthyroid and control group, hypothyroid group was established by daily intraperitoneal injections with propylthiou raci(PTU, 10.0 mg/kg body weight) for 6 weeks and hyperthyroid group with L-Thyroxine (L-T4, 0.5 mg/kg body weight) for 3 weeks. Radioimmunity method was used to assay the levels of serum T3 and T4, immunohistochemical S-P technology to assay the levels of Syt Ⅰ protein in hippoeampus CA1, CA3 and dentate gyrus (DG). The layers analyzed in the different subfields include the polymorphic cell layer(the stratum oriens, SO), pyramidal cell layer(PCL), stratum radiatum (SR), lacunosum-molecular layer (SLM) in CA1 and CA3, granular cell layer(GL) and molecular layer(ML) in DG. Results The levels of serum T3 and T4[(0.34±0.12), (41.03± 11.37)nmol/L]in the hypothyroid rats were significantly lower than those in the control group[(0.65±0.15), (55.20±10.68)nmol/L, P < 0.01 or < 0.05], and the positive granule of Syt Ⅰ was significantly lower in PCL and SR of CA1 and CA3, GL of DG. The average optical value responsible for Syt Ⅰ immunoreactivity was obviously reduced in SO(0.048±0.007), PCL(0.299±0.035), SR(0.042±0.007), SLM(0.038±0.006) of CA1, PCL(0.085± 0.019), SR(0.040±0.011), SLM (0.038±0.006) of CA3, GL (0.076±0.019) of DG than normal controls (0.068± 0.014, 0.376±0.053, 0.053±0.008,0.056±0.009,0.118±0.026,0.052±0.010,0.053±0.009,0.099±0.015; P< 0.01 or < 0.05). Serum T3 and T4 levels [(1.43±0.30), (157.18±19.95)nmol/L]of hyperthyroid rats were significantly higher than those of control group(P < 0.01). The value was reduced in PCL(0.322±0.050), SR(0.039±0.006), SLM (0.042±0.006) of CA1, PCL(0.098±0.034), SR(0.046±0.013), SLM(0.046±0.010) of CA3 and GL(0.085± 0.024), ML (0.042±0.009) of DG (P < 0.05 or < 0.01). Conclusion Adult-onset of hypothyroidism and hyperthyroidism can reversibly decrease the expression of Syt Ⅰ in CA1, CA3 and DG regions of hippocampus.