Effects of triiodothyronine and imipramine on basal 5-HT levels and 5-HT(1) autoreceptor activity in rat cortex

Clinical studies have shown that triiodothyronine (T3) both augments and accelerates the therapeutic response to antidepressant drugs, particularly tricyclics. There is evidence that this effect is mediated by the serotonergic system. We show here that T3 administered daily for 7 days over the range 0.02-0.5 mg/kg increases basal serotonin (5-hydroxytryptamine, 5-HT) levels, as measured by in vivo microdialysis in rat cortex, in a dose-dependent fashion. All the doses of T3 examined reduced 5-HT(1A) autoreceptor activity, as measured by the effect of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.05 mg/kg s.c.) to decrease 5-HT levels in frontal cortex. T3 administered daily for 14 days at 0.02 mg/kg also reduced 5-HT(1B) autoreceptor activity, as measured by the effect of locally administered 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP 93129, 10 microM) to decrease 5-HT levels. In animals administered imipramine (10 mg/kg/day by osmotic minipump) concurrently with T3 injections, no further changes in either 5-HT(1A) or 5-HT(1B) autoreceptor activity were seen. We suggest that the effect of T3 to accelerate the therapeutic actions of antidepressant drugs may be due to a combination of the actions of T3 at autoreceptors and the actions of the drugs at postsynaptic 5-HT(1A) receptors.     

三碘甲腺原氨酸（T3）对大鼠胰岛体外培养时胰岛素分泌的影响

本文检测了离体大鼠胰岛在１．５４或１５．４ｔμｍｏｌ／ＬＴ＿３浓度下体外培养５天后葡萄糖诱发胰岛素分泌水平。结果表明，当培养液内葡萄糖浓度为１１．１与２２．０ｍｍｏｌ／Ｌ时，葡萄糖诱发急相或慢相胰岛素释放，Ｔ＿３（ｌ．５４μｍｏｌ／Ｌ）处理组胰岛与对照组比较均显著降低。提示高糖情况下，Ｔ＿３对葡萄糖诱发离体胰岛胰岛素分泌有直接的延迟性抑制作用，而胰岛内胰岛素含量改变可能是导致葡萄糖诱发胰岛素分泌减低的重要因素之一。     

Histology and immunocytochemistry of differentiated thyroid carcinomas do not predict radioiodine uptake: A clinicomorphological study of 62 recurrent or metastatic tumours

Summary Sixty-two metastases or recurrences of differentiated thyroid carcinomas were investigated using conventional histology and immunocytochemistry for thyroglobulin (TG), thyroxine (T₄) and triiodothyronine (T₃). In each patient,¹³¹I total body scans had been performed 4–10 weeks before surgery. Twenty-seven of the 62 tumours exhibited a predominance of follicles (A₁), while 35 either exclusively or predominantly consisted of papillae or, in the case of follicular carcinomas, were predominantly trabecular or solid in structure (A₂). TG and T₄ immunoreactivity was observed in 60 cases, only 4 of these also expressing T₃. Positive radioiodine uptake (RIU) was noted in 27 of 62 (44%) cases (A₁: 18/ 27=67%; A₂: 9/35=26%), 25 of which showed intraluminal TG and T₄ positivity. Two follicular carcinomas showing RIU lacked follicular lumina, but exhibited strong diffuse cytoplasmic positivity for both TG and T₄. In another 95 differentiated thyroid carcinomas, the structure of primary and secondary lesions was assessed. Of these, 27 (28%) showed a discordant pattern (A₁/A₂ or A₂/A₁) when comparing the structure of primary and secondary lesions. Our data suggest that differentiated thyroid carcinomas show a dissociation of TG/T₄ expression and RIU, defects of iodine uptake and storage being found more frequently than a depression of TG and T₄ synthesis. Intact synthesis of TG and T₄, but not of T₃ may be regarded as a prerequisite for RIU. Positive RIU is based on the presence of mature neoplastic follicles containing TG and T₄ immunoreactive colloid and among follicular carcinomas, positive RIU may be encountered in neoplasms lacking follicular lumina but exhibiting strong cytoplasmic TG and T₄ staining. Finally, the RIU of recurrent and metastatic PC and FC is not predictable from histological features of the primaries.Dedicated to Prof. Christoph Hedinger, former director of the Institute of Pathology, University of Zürich, on the occasion of his 75th birthday     

针刺治疗突眼性甲状腺肿临床疗效观察

目的 :观察针刺治疗突眼性甲状腺肿的疗效。方法 :随机将 6 7例患者分为针刺观察组和西药对照组。结果 :针刺疗法治疗此病在血清总甲状腺素、三碘甲状腺原氨酸含量下降的同时 ,突眼症有所好转 ,同现行的西药疗法相比有一定的优越性 ,针刺治疗前后血清总甲状腺素、三碘甲状腺原氨酸、促甲状腺素含量对比 (P <0 0 0 1) ,有明显差异。结论 :针刺疗法治疗突眼性甲状腺肿对缓解和消除眼征、症状有良好的效果 ,在临床上有一定的实用价值     

Electrophysiological effects of triiodothyronine and propranolol

The effects of triiodothyronine (T3), T3 combined with propranolol, and propranolol alone on somatosensory evoked responses (SER) and EEG were studied in 2 groups each of 6 male volunteer subjects. The following results were obtained: (1) T3 increased SER amplitude during the first 100 ms after stimulus. (2) Addition of propranolol elimi nated the SER amplitude increase resulting from T3 administration. (3) Neither T3 nor T3 plus propranolol significantly altered the mean level or the temporal variability of EEG amplitude and frequency. (4) There were no significant effects of propranolol alone on SER and EEG measures.Research supported (in part) by Grant MH12507, from the U.S. Public Health Service.     

Measurement of reverse triiodothyronine for the newborn screening of thyroid disorders

Neonates were tested for filter paper blood spot reverse T₃ (rT₃) and Thyroxine (T₄). A significant correlation was found between T₄ and rT₃ levels, however, there was no correlation between low rT₄ and corresponding rT₃ levels. The study shows rT₃ measurement is not more sensitive than T₄ for screening neonates for thyroid disorders and measurement of both T₄ and rT₃ levels does not help in screening out false low T₄ values commonly observed in screening programs.     

The effect of triiodothyronine on the cardiac mRNA

Cardiac hypertrophy was induced in rats by daily injections of L-triiodothyronine (0.2 mg/kg body wt, s.c., 1 to 3 days). Regression of hypertrophy was studied after 3 days of injection for a period of 1 to 16 days. Cardiac RNA was isolated by phenolextraction, mRNA by affinity chromatography of cardiac total RNA on oligo-dT-cellulose. In addition, cardiac mRNA was also quantitated by hybridization to ³H-Poly(U). After 3 days of T₃-treatment, the extractable amount of cardiac total RNA increased from 759 ± 181 μg/g heart (controls) to 980 ± 119 μg/g heart (T₃-rats), and that of mRNA from 24.7 ± 2.0 (controls) to 39.4 ± 7.0 (T₃-rats), increases of 29.1% (total RNA) and 59.5% (mRNA). 16 days after cessation of T₃-treatment, total RNA and mRNA levels had returned to normal. The increase in cardiac mRNA in T₃-rats was investigated in further detail by in vitro translation of the isolated mRNA in the mRNA-dependent reticulocyte lysate system. Incorporation of ³⁵S-methionine into total protein was identical for cardiac mRNA from control and T₃-rats. Separation of the in vitro synthesized proteins on SDS-Polyacrylamide-Slabgels revealed the complete synthesis of actin, troponin-T, tropomyosin, myoglobin and myosin-light-chains 1 and 2. The mRNAs coding for these proteins represented identical fractions of total mRNA in control and T₃-rats. This leads to the conclusion that T₃ had stimulated the synthesis of all of these specific mRNAs in an unselective manner. From our data and from the results of other authors we conclude that changes in cardiac mRNA levels are the major regulatory factor in causing changes in cardiac protein synthesis rates leading to cardiac hypertrophy in hyperthyroidism.     

Lack of stimulation of kidney Na−K-ATPase by thyroid hormones in long-term thyroidectomized rabbits

The effects of long-term thyroidectomy and of subsequent triiodothyronine administration on kidney Na–K-ATPase were studied at the level of single nephron segments and were compared to the short-term effects previously reported. After 8–11 weeks, thyroidectomy resulted in a marked decrease in Na–K-ATPase activity in all the segments of the rabbit nephron, the proximal tubule, the thick ascending limb of Henle's loop, the distal convoluted tubule and the collecting tubule. Within this delay, thyroidectomy also decreased the ouabain-insensitive Mg-ATPase activity, the basal and hormone-stimulated adenylate-cyclase activity, and the volume of tubular epithelium in all the segments where these parameters were measured. Administration of 50 g/kg body weight triiodothyronine to 8–11 weeks thyroidectomized rabbits did not restore Na–K-ATPase activity in any nephron segment within 48 h. These observations are different from those reported in animals thyroidectomized only 1 week before study since, within this latter delay, (1) thyroidectomy altered specifically Na–K-ATPase activity, (2) this action was observed on the proximal and collecting tubules exclusively and, (3) triiodothyronine administration corrected Na–K-ATPase alterations after 49 h. Results of the present study indicate that in the long term, thyroidectomy has a wide spectrum of renal effects which involves the whole nephron and most cellular functions. The tubular involution induced by longterm thyroidectomy is probably responsible for the inability of kidney cells to quickly increase their Na–K-ATPase activity in response to hormonal stimulation.     

A 3,3′,5′-triiodothyronine (reverse T3) radioimmunoassay

Summary In this paper are reported the results obtained by a simple, reproducible and sensitive rT3 RIA, in unextracted serum, using the PEG separation technique. The linear correlation coefficient of the results obtained from extracted and unextracted sera, in a population of 60 adults and 35 child controls was 0.984, with a minimal spread of the data.