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PubMed1991

Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus.

BACKGROUND: Data on human fetal thyroid function have largely been derived from histologic studies or studies of cord-blood samples obtained at hysterotomy or delivery. These data may not represent true normal values. Cordocentesis (ultrasound-guided blood sampling from the umbilical cord) is a technique that allows investigation of physiologic processes in fetuses not under stress. METHODS: We measured serum thyroid-stimulating hormone, total and free thyroxine (T4), total and free triiodothyronine (T3), and thyroxine-binding globulin in blood samples from 62 fetuses. The samples were obtained by cordocentesis (n = 58) or cardiocentesis (n = 4) at 12 to 37 weeks of gestation. Maternal serum samples were obtained immediately before fetal blood sampling. RESULTS: Fetal serum thyroid-stimulating hormone, thyroxine-binding globulin, and total and free T4 and T3 concentrations increased significantly with the length of gestation (P less than 0.001). The only significant association among these variables, independent of the length of gestation, was between thyroid-stimulating hormone and free T4 (P less than 0.0001). Maternal serum concentrations of these variables did not change during gestation, and there was no significant relation between fetal and maternal values. Most fetal serum concentrations of thyroid-stimulating hormone were higher, whereas most serum total and free T3 concentrations were lower than the respective values for normal adults. The fetal serum total T4, free T4, and thyroxine-binding globulin values reached the level of the mean adult values at approximately 36 weeks of gestation. CONCLUSIONS: The increases in fetal serum concentrations of thyroid-stimulating hormone, thyroxine-binding globulin, and total and free T4 and T3 during gestation reflect increasing maturation of the pituitary, thyroid, and liver. The finding of increasing fetal serum concentrations of thyroid-stimulating hormone in the presence of increasing thyroid hormone concentrations suggests that the sensitivity of the fetal pituitary gland to negative feedback is limited or is counterbalanced by increasing stimulation by thyrotropin-releasing hormone from the hypothalamus.

Female↗
PubMed1993

Iodine regulation of endothelin-1 gene expression in cultured porcine thyroid cells: possible involvement in autoregulation of the thyroid.

We studied the regulation of endothelin (ET)-1 gene expression in porcine thyroid cells in culture. First, we demonstrated prepro-ET-1 mRNA in porcine thyroid cells. The level of the mRNA was increased by phorbol 12-myristate 13-acetate (TPA), a protein kinase C stimulator, but was decreased by TSH (1 mU/mL). However, transforming growth factor-beta and interleukin-1 beta had no effect. The amount of immunoreactive (ir)-ET-1 secreted from the cells was also increased by TPA and was decreased by TSH. Next, we studied the effect of iodide, as iodide has various effects on thyroid cells. NaI (100 microM) increased the prepro-ET-1 mRNA level. The effect of NaI was attenuated by 1 mM methimazole (MMl). The amount of ir-ET-1 released from the cells was also increased by the NaI treatment and the increase was also attenuated by MMl. These observations indicate that ET-1 gene expression is induced by organified iodine compounds in thyroid cells in a manner very similar to the inhibitory actions of iodide on thyroid cell function. The protein synthesis inhibitor, cycloheximide, superinduced prepro-ET-1 mRNA within 4 h, but NaI did not. The difference between cycloheximide and NaI suggests that the iodine effect on the gene expression is not due to nonspecific inhibition of protein synthesis. Together with our previous findings that porcine thyroid cells have ET-1 receptors and that ET-1 modulates iodine metabolism, we speculate that ET-1 produced by thyroid cells is involved in thyroid autoregulation including thyroid blood flow.

Animals↗
PubMed1996

IFN-gamma has a protective role against thyroid-specific autoantibody production in severe combined immunodeficient (SCID) mice xenografted with Graves' thyroid tissue.

We studied the effects of exogenous human IFN-gamma or neutralizing monoclonal antibody (mAb) to IFN-gamma on xenografted human Graves' thyroid tissue in severe combined immunodeficient (SCID) mice to investigate a possible role of IFN-gamma in the pathogenesis of human Graves' disease. Human thyroid tissues from four patients with Graves' disease were xenografted into SCID mice. Two weeks after xenografting, mice were divided into three groups with human IgG levels similar to each other. Mice in the first group were treated with human IFN-gamma daily for 6 weeks; mice in the second (similar) group were treated with an mAb to IFN-gamma; mice in the third group were given mouse IgG only (control group). Blood samples were taken every 2 weeks for human IgG and thyroid-specific autoantibodies (Tg-Ab, TPO-Ab, and thyroid-stimulating antibody). After 6 weeks' treatment, mice were killed, and the thyroid xenograft was examined for thyrocyte HLA-DR expression. Human IgGs were produced equally in all three groups; mice treated with IFN-gamma showed significantly lower amounts of thyroid autoantibodies than those in the control group. Thyrocyte HLA-DR expression was markedly increased in xenografts from mice with IFN-gamma administration. On the other hand, anti-IFN-gamma mAb injection caused only slight suppression of HLA-DR expression on xenografted thyroid cells. In conclusion, IFN-gamma may down-regulate the production of thyroid-specific autoantibodies but not human IgG, at least under these circumstances; there thus may be specific inhibitory effects of IFN-gamma against thyroid-specific autoantibody production of intrathyroidal plasma cells, and this animal model may help to elucidate the possible role of cytokines in the pathogenesis of Graves' disease.

Animals↗
PubMed1997

Calmodulin purified from human and porcine thyroids inhibits thyrotropin binding to porcine thyroid cells.

A thyrotropin (TSH) binding inhibiting protein (TBIP) that inhibits TSH binding to the TSH receptor, as determined by the TSH receptor assay, was purified from human and porcine thyroid. The soluble fraction (100,000 x g supernatant of Graves' thyroid homogenate) was precipitated with ammonium sulfate between 1.75 to 2.5 mol/L. TBIP was eluted by 0.5 mol/L sodium chloride (NaCl) containing 20 mmol/L Tris buffer, pH 7.5 from a Q-sepharose column. The unbound fraction from concanavalin A (Con A) and blue-sepharose was gel-filtered using sephadex G-100, and finally purified by Resource Q column chromatography. Purified TBIP was confirmed as a single protein band of 17 kDa. The TBI activity in the purified TBIP was significantly decreased by either etnylene glycol tetraacetate (EGTA) (1 mmol/L) or antibody to calmodulin (CaM) in the TSH receptor assay. The TBIP was confirmed immunologically as CaM by the Ouchterlony method using antibody for CaM. These findings demonstrated that the TBIP purified from human and porcine thyroids was, in fact, CaM. We examined the effects of TBIP purified from human thyroid on bovine TSH (bTSH) or thyroid stimulating antibody (TSAb)-stimulated cyclic adenosine monophosphate (cAMP) production in porcine thyroid cells (PTC). TBIP itself did not increase basal levels of cAMP production, but inhibited bTSH (100 mU/L)-stimulated cAMP production. However, TBIP did not inhibit cAMP production stimulated by TSAb-IgG and various thyroid stimulators (GTPgammaS, forskolin and pituitary adenylate cyclase-activating polypeptide [PACAP, 27 and 38 amino acids]). Authentic CaM purified from bovine brain behaved in a manner similar to that of TBIP. These data showed that CaM differentially affects thyroid stimulation by TSH and TSAb in intact thyroid cell experiments.

Animals↗
PubMed1990

Autoimmune thyroiditis induced in mice depleted of particular T cell subsets. III. Analysis of regulatory cells suppressing the induction of thyroiditis.

It has previously been demonstrated that T cell clones with potentials to induce autoimmune thyroiditis exist in lymphoid organs from normal healthy individuals. The present study investigates the nature of regulatory cells co-existing in a normal lymphoid cell population to prevent the activation of these thyroiditis-inducing T cells. T cell-depleted (C57BL/6 x C3H/He) F1 mice (B cell mice) were prepared by adult thymectomy and injection of anti-thymocyte serum, followed by lethal X-irradiation and bone marrow reconstitution. Typical thyroiditis was induced in these B cell mice by i.v. administration of Lyt-1dull T cells but not of whole T cells from normal syngeneic mice. Additional injection of normal thymocytes into B cell mice which had been transferred with the Lyt-1 dull T cells resulted in complete prevention of thyroiditis induction. Mature thymocytes were responsible for this regulatory function and such regulatory cell activity was also found in peripheral lymphoid cells such as spleen cells. These regulatory cells exerted their capacity to prevent thyroiditis in cell dose-dependent and injection timing-dependent manners; thyroiditis was prevented when they were injected in cell doses of greater than 1.5 x 10(7)/mouse and before the initiation of the thyroiditis lesion. Most interestingly, the phenotypes of regulatory cells were Thy-1+ and L3T4+. Since the thyroiditis-inducing Lyt-1 dull T cells has previously been shown to be of L3T4+, these results indicate that there exist functionally heterogeneous subsets in an L3T4+ T cell population and that some L3T4+ T cells function as regulatory cells to prevent the activation of thyroiditis-inducing L3T4+ T cells co-existing in the normal lymphoid cell population.

Animals↗
PubMed1996

Clinical presentations and treatment for 74 occult thyroid carcinoma. Comparison with nonoccult thyroid carcinoma in Taiwan.

There is limited clinical information of Chinese patients with occult well-differentiated thyroid cancer (OTC). The purposes of this study were to elucidate the clinical presentations and results of treatment in the patients with OTC in Taiwan. The data of 568 patients with pathologically verified papillary and follicular thyroid carcinomas who received primary treatment in Chang Gung Memorial Hospital were retrospectively reviewed. Seventy-four of 568 patients with well-differentiated thyroid carcinoma were OTC; those included 71 papillary thyroid carcinomas and three follicular carcinomas. Among the 74 OTC patients, five cases (6.8%) presented with distant metastases, but 41 cases (10.1%) were found with distant metastases in 416 nonoccult thyroid cancer (NOTC) (p = 0.509). In the five OTC with distant metastases, there were three papillary carcinomas and two follicular carcinomas. Only one case (1.4%) died of distant metastasis of the occult papillary thyroid carcinoma versus 20 cases out of the total 568 (4.1%) well-differentiated thyroid carcinomas. After statistical analysis, there were no differences between the survival rates of OTC and NOTC patients. In the present study, 1 month postoperative serum thyroglobulin level could be used as prognostic factor in both OTC and NOTC patients. Only 54.17% of OTC patients were diagnosed as thyroid cancer by thyroid ultrasonography with the fine needle aspiration cytology. In conclusion, most OTC had relatively benign clinical courses, but distant metastases may result in mortality still observed. Therefore, OTC should be treated as NOTC, since relatively high rate of distant metastases were found in the patients with OTC.

Adenocarcinoma, Follicular↗
PubMed2001

Superiority of iodine-123 compared with iodine-131 scanning for thyroid remnants in patients with differentiated thyroid cancer.

PURPOSE: Iodine-123 is a pure gamma emitter and has excellent characteristics for imaging with modern scintillation cameras. The goal of this study was to compare the performance of I-123 and I-131 as imaging agents for whole-body scanning in patients with differentiated thyroid cancer undergoing ablation for thyroid remnants after initial surgery. METHODS: Fourteen patients with differentiated thyroid cancer who had undergone near-total thyroidectomy and had serum thyroid-stimulating hormone levels greater than 40 mU/I underwent diagnostic scanning 5 hours after administration of 48 to 56 MBq (1.3 to 1.5 mCi) I-123 and 48 hours after administration of 111 MBq (3 mCi) I-131. After receiving ablative I-131 therapy, they also underwent whole-body planar imaging 7 days later. The diagnostic I-123 and I-131 scans were compared with each other and with the post-therapy images by two nuclear medicine physicians and one endocrinologist. RESULTS: The diagnostic scans revealed 35 foci in the thyroid bed and neck. The I-123 images showed all 35 foci, but only 32 of the 35 foci (91 %) were seen on the I-131 scans. The findings of pre- and post-therapy scans were concordant in 11 of 13 patients, and the same general sites of uptake (left and right thyroid bed, midline) were revealed on both sets of images. In one patient, a focus seen on the diagnostic I-123 and I-131 images was not visualized on the post-therapy scan and was thought to represent possible stunning. An additional area of uptake in the lower right neck and upper mediastinum was present on the post-therapy scan of another patient, but it was not seen on diagnostic images. CONCLUSION: These results show improved quality of imaging with 50 MBq (1.5 mCi) I-123 compared with 111 MBq (3 mCi) I-131 for whole-body scanning in patients with differentiated thyroid cancer undergoing thyroid remnant ablation. I-123 imaging may prove to be the preferred procedure in such settings in patients with differentiated thyroid cancer.

Adenocarcinoma, Follicular↗
PubMed1983

Thyroid graft rejection between C57BL/6 and H-2Kb mutant mice. Differences in the immunogenic expression of the mutated molecule on thyroids of six different mutants.

Mice that possess mutations in the H-2 region were selected by means of skin grafting. We tested the survival time of thyroid grafts transplanted between C57BL/6 mice and their descendent H-2Kb mutant mice and compared the kinetics of skin versus thyroid graft rejection in each of the mouse strain combinations tested. The results demonstrated that reciprocal thyroid grafts between C57BL/6 mice and bm1, bm3, bm4, bm5, and bm6 mutants are accepted for long periods. The bm8 mutant appeared to be an exception because a small fraction of reciprocal thyroid grafts were rejected between bm8 and C57BL/6 mice. Transplantation of C57BL/6 mice with skin grafts from bm1, bm3, bm4, and bm8 donors induced rejection of subsequent thyroid grafts syngeneic with the skin. Thyroid grafts of bm5 and bm6 were not rejected by C57BL/6 mice even after preimmunization with bm5 and bm6 skin grafts. In contrast to skin grafts, innoculation of C57BL/6 mice with 50 X 10(6) spleen cells from mutant mice failed to immunize the recipients and induce rejection of mutant thyroid grafts. The results indicate that skin graft rejection assays and in vitro cell-mediated lympholysis (CML) typing can not always predict the consequence of transplantation of organs such as thyroid, and also that alterations in the H-2Kb molecule as a result of spontaneous mutations can give rise to mutated molecules that differ in their immunogenic and antigenic properties when expressed on thyroid cells, as compared with skin.

Animals↗
PubMed2006

Immunohistochemical analysis of thyroid-specific transcription factors in thyroid tumors.

Thyroid transcription factor 1 (TTF1), thyroid transcription factor 2 (TTF2) and paired box gene 8 (Pax8) are demonstrated to play a crucial role for the differentiation and organogenesis of thyroid follicular cells. Their roles in thyroid carcinogenesis are not very clear. Because dedifferentiation is a common process in thyroid carcinogenesis, thyroid-specific transcription factors seem also to be involving in thyroid carcinogenesis. The purpose of the present paper was to investigate their expression in a broad spectrum of follicular cell tumors in different degrees of differentiation, from well-differentiated benign follicular adenoma to anaplastic carcinoma. Medullary (C cell) carcinoma was also included in the investigation. Results of immunohistochemical staining showed that nuclear localization of these transcription factors was gradually decreased corresponding to the progressive dedifferentiation of thyroid tumors. Also, abnormal cytoplasmic accumulation of TTF2 and Pax8 was detected in many tumors samples, which may indicate a subtle regulation mechanism on the function of these transcription factors. In conclusion, abnormal expression of TTF1, TTF2 and Pax8 was closely related to thyroid tumorigenesis.

Adenoma↗
PubMed1991

Thyroid-specific enhancer-binding protein (T/EBP): cDNA cloning, functional characterization, and structural identity with thyroid transcription factor TTF-1.

A cDNA clone encoding a thyroid-specific enhancer-binding protein (T/EBP) was isolated from a rat thyroid-derived FRTL-5 cell lambda gt 11 expression library, using a double-stranded oligonucleotide probe. This oligonucleotide was previously demonstrated to have the strongest binding affinity among three cis-acting DNA elements within the thyroid-specific enhancer region located 5.5 kbp upstream of the human thyroid peroxidase gene transcription start site. Nucleotide and deduced amino acid sequences of the cDNA revealed that T/EBP is identical to the previously reported thyroid-specific transcription factor 1 (TTF-1), which binds to the promoter of the rat thyroglobulin gene and controls its thyroid-specific expression. Expression of the T/EBP cDNA under control of the human cytomegalovirus major immediate-early gene promoter conferred thyroid-specific enhancer activity of as high as 26-fold to nonpermissive human hepatoma HepG2 cells when cotransfected with a vector containing 6.3 kbp of upstream sequence of the human thyroid peroxidase gene connected to a luciferase reporter gene. T/EBP was further expressed in HepG2 cells by using the vaccinia virus expression system. The expressed protein was partially purified by using sequence-specific affinity column chromatography and was further shown, by gel mobility shift experiments, to specifically bind to the enhancer-derived double-stranded oligonucleotide. These results clearly indicate that the binding of T/EBP (TTF-1) to the specific cis-acting enhancer element is largely responsible for thyroid-specific enhancer activity.

Animals↗
PubMed2004

Autoimmune thyroiditis and anti-thyroid antibodies in primary Sjogren's syndrome: a case-control study.

OBJECTIVE: To determine the frequency of antithyroid antibodies and the presence of autoimmune thyroiditis among patients with primary Sjögren's syndrome. DESIGN: A case-control study. METHODS: 53 consecutive patients with primary Sjögren's syndrome, 30 with rheumatoid arthritis, 12 with secondary Sjögren's syndrome associated with rheumatoid arthritis, 17 with autoimmune thyroiditis, and 53 apparently healthy controls were studied for anti-TG and anti-TPO antibodies as well as serum thyroid hormones and TSH levels. RESULTS: The overall frequencies of thyroid antibodies were 6/53 (11%) in primary Sjögren's syndrome, 2/30 (7%) in rheumatoid arthritis, 2/12 (17%) in secondary Sjögren's syndrome, 4/53 (8%) in healthy controls, and 16/17 (94%) in autoimmune thyroiditis. There was no difference in the frequency of the thyroid antibodies among the groups if patients with autoimmune thyroiditis were excluded (p = 0.415 for anti-TPO; p = 0.275 for anti-TG; p = 0.696 for either anti-TG and/or anti-TPO). Only two patients with primary Sjogren's syndrome had clinical hypothyroidism associated with autoimmune thyroiditis. CONCLUSIONS: In this Turkish population, no association between primary Sjögren's syndrome and autoimmune thyroiditis was found.

Adult↗
PubMed1975

Thyroidal triiodothyronine and thyroxine in Graves' disease: correlation with presurgical treatment, thyroid status, and iodine content.

To evaluate the potential contribution of thyroidal secretion to the relative excess of triiodothyronine (T3) production in hyperthyroidism and to investigate the effects of treatment, iodine (127I), T3 and thyroxine (T4) were measured in digests of thyroid tissue obtained at surgery from 13 patients with Graves' disease. In 11 normal human thyroid glands, 127I content was 630 +/- 60 (all values mean +/- SE in mug/ wet weight) T4, 254 +/- 39 and T3 21 +/-3. The T4I was 26 +/- 3% of the total iodine and the molar ratio T4/T3 was 11 +/- 1. The 13 patients with Graves' disease were divided into three groups. Eleven were clinically euthyroid (Groups I and II) and had received either iodide or iodide plus a thiourea derivative before surgery. Two subjects (Group III) received only propranolol. In Group I (n = 8), mean thyroidal 127I content was 320 +/- 50, T4 was 115 +/- 9 and T3 22 +/- 4. The molar ratio T4/T3 was 5.9 +/- 1 and T4I was 26 +/- 2% of the total. Group II patients (3) had the lowest preoperative serum T4 (less than 2.5 mug/dl) and T3 (less than ng/dl) concentrations with TSH elevated in only one (7 muU/ml). Thyroidal 127I was 100 +/- 26, T49 +/- and T3 1.3 +/- 0.3. The % T4I was 5 +/-2. The two chemically hyperthyroid subjects had a mean tissue 127I of 450; T4, 295 and T3, 56, the T4/T3 ratio was 4.5 and % T4I was 42. There was no correlation between tissue 127I and T4/T3 within either the normal or Graves' disease group. Since adequate clinical and chemical control of hyperthyroidism with antithyroid drugs and iodine was attained in the 8 Group I subjects without a decrease in the % T4I or T3I below that of normal thyroids, it suggests that inhibition of iodotyrosine coupling is not required for this effect. The % T4I was below normal only in patients with marked suppression of serum T4 and T3 concentraions. The lack of correlation between tissue 127I and T4/T3 ratio in the treated patients suggests that the lower T4/T3 ratio in Graves' thyroids is independent of intrathyroidal iodine concentrations. This hypothesis is strengthened by the similarly low T4/T3 ratio in untreated subjects with near normal tissue 127I content. Assuming that the thyroid hormones are secreted in the ratios present in these digests, one can estimate that direct secretion by the thyroid could contribute most, of not all, of the excess T3 production in Graves' disease.

Adolescent↗
PubMed1989

Antibodies to human thyroid peroxidase in autoimmune thyroid disease: studies with a cloned recombinant complementary deoxyribonucleic acid epitope.

Previous studies carried out by screening a lambda gt11 human thyroid cDNA library with serum samples from selected patients with Hashimoto's thyroiditis and a polyclonal antibody to porcine thyroid peroxidase (TPO) confirmed, at the molecular level, that TPO is a major component of the thyroid microsomal antigen (M). That investigation led to the isolation of a clone (C2) which encodes an 85-amino acid segment of TPO and harbors a major epitope recognized by serum from several patients with autoimmune thyroid disease that contained anti-M autoantibodies (MAb). In this study, C2 antigen that was produced as a beta-galactosidase fusion protein was used to establish an enzyme-linked immunoabsorbent assay for the detection of anti-C2 autoantibodies (C2Ab). C2Ab then were assayed in 191 patients with different autoimmune and nonautoimmune thyroid disorders, and 50 patients with nonthyroidal autoimmune diseases. The results were compared with the titers of anti-TPO antibodies (TPOAb; as detected by monoclonal antibody-assisted RIA) and MAb (as detected by passive hemagglutination). Positive C2Ab was found in the serum of 85 of 136 (63%) patients whose serum contained TPOAb and/or MAb. A significant positive correlation was found between the levels of C2Ab and those of TPOAb (r = 0.76; P less than 0.001) or MAb (r = 0.69; P less than 0.001), which was independent of the type of underlying autoimmune thyroid disorder. Low levels of C2Ab also were found in 10 of 105 (9%) serum samples that did not contain TPOAb. Western blot analysis carried out on the latter samples showed that in 2 samples the apparent C2Ab reactivity was due to the presence of antibodies reacting with beta-galactosidase. In conclusion, we confirmed the validity of screening lambda gt11 cDNA human thyroid libraries to better characterize thyroid autoantigens and demonstrated the feasibility of using recombinant proteins to establish diagnostic assays for autoantibodies.

Antibodies↗
PubMed1997

Increased expression of the Na+/I- symporter in cultured human thyroid cells exposed to thyrotropin and in Graves' thyroid tissue.

The Na+/I- symporter (NIS) is important in hormone synthesis in the thyroid gland. NIS activity, as reflected by I- uptake, was increased by TSH (1 mU/mL) or forskolin (10 mumol/L) in primary cultured human thyroid cells. Northern blot analysis revealed that incubation of these cells with TSH or forskolin for 24 h increased the abundance of NIS messenger ribonucleic acid (mRNA) 2.3- and 2.5-fold, respectively. Immunoblot analysis revealed 2.7- and 2.4-fold increases, respectively, in the amount of NIS protein after 48 h, suggesting that elevated levels of intracellular cAMP induced the expression of NIS in human thyrocytes. We then studied the levels of NIS mRNA and protein in Graves' thyroid tissue and found that the amount of NIS mRNA in thyroid tissue from individuals with Graves' disease (n = 5) was 3.8 times that in normal thyroid tissue (n = 5). The abundance of NIS mRNA was significantly correlated with that of thyroid peroxidase or thyroglobulin mRNAs, but not with that of TSH receptor mRNA, in the Graves' and normal thyroid tissue specimens. The amount of NIS protein was also increased 3.1-fold in Graves' thyroid tissue compared with that in normal thyroid tissue. The increased expression of NIS may thus contribute to the development of Graves' disease.

Blotting, Northern↗
PubMed2001

Construction of gene therapy vectors targeting thyroid cells: enhancement of activity and specificity with histone deacetylase inhibitors and agents modulating the cyclic adenosine 3',5'-monophosphate pathway and demonstration of activity in follicular and anaplastic thyroid carcinoma cells.

Thyroid carcinoma accounts for the majority of deaths from endocrine cancers. Although effective therapies exist for well differentiated tumors, the treatment options for poorly differentiated and anaplastic tumors are much less effective. In the present study we demonstrate that the thyroglobulin (Tg) promoter can be used to direct specific expression of either luciferase or thymidine kinase in thyroid cancer cells. Furthermore, using a putative enhancer element for the Tg gene, the activity of the Tg promoter in and its specificity for thyroid cells were enhanced. In transient transfectants or in stably transfected thyroid carcinoma cells, treatment with the histone deacetylase inhibitors, depsipeptide (FR9012228) and sodium butyrate, alone or in combination with 8-bromo-cAMP, resulted in further enhancement. In experiments in which the herpes simplex virus thymidine kinase (HSV-TK) gene was driven by the Tg promoter and the putative enhancer, HSV-TK expression and ganciclovir sensitivity were augmented. Similar results were obtained in two cell lines derived from a follicular thyroid carcinoma and in two anaplastic thyroid carcinoma cell lines. In summary, we report the construction of a suicide HSV-TK vector with preferential toxicity for thyroid cells. The results in anaplastic thyroid carcinoma cells suggest that it may be of use in the full spectrum of thyroid malignancies.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1976

[Studies on the thyrotropin receptor in the thyroid: positive cooperativity of Concanavalin A binding and its biphasic effects on thyroid activation induced by thyrotropin (author's transl)].

Concanavalin A (Con A) was tested for its ability to affect thyroid activation induced by the thyroid stimulators in mouse thyroid tissues. Con A was found to have the biphasic stimulatory and inhibitory effects of thyrotropin (TSH)-induced cyclic AMP formation and endocytosis, a step in thyroid hormone secretion, in mouse thyroid tissues. Low concentrations of Con A potentiated TSH-stimulated cyclic AMP formation and endocytosis. In contrast, high concentrations of Con A markedly inhibited TSH stimulations. These effects were reversed by the addition of methyl-alpha-D-glucoside to the second preincubation medium (without Con A) prior to TSH. A high concentration of Con A alone did not depress the basal levels of cyclic AMP or basal glucose oxidation in thyroid tissues. A high concentration of Con A also inhibited cyclic AMP formation induced by prostaglandin E2 and the long-acting thyroid stimulator (LATS). Binding of 125I-labeled Con A to thyroid tissues increased with time up to 75 min and was very slowly reversible after attainment of equilibrium. Binding was directly proportional to tissue weight. Scatchard plot analysis on the binding of 125I-labeled Con A to thyroid tissues indicated a positive cooperativity which seemed to be well correlated to the biphasic effects.

Animals↗
PubMed1984

Relation of structural polarity to responses of cyclic 3', 5'-adenosine monophosphate accumulation and thyroid hormone release in cultured human thyroid follicles.

The relationship of structural polarity to functional activities was examined in cultured human thyroid follicles, which were isolated from the thyroid gland of patients with Graves' disease by collagenase treatment. Structural polarity was examined morphologically by electron microscopy, while the functional response to bovine TSH was examined by measuring intracellular cAMP accumulation and T3 release. In freshly isolated thyroid follicles, structural polarity was normal and TSH induced significant cAMP accumulation but no significant release of T3. After culture for 5 days the structural polarity of thyroid follicles became inverted in the absence of thyroid stimulators, but normal polarity was retained in the presence of TSH or dibutyryl cAMP [Bu)2 cAMP). The response to TSH of cAMP accumulation increased markedly after culture in either the presence or absence of TSH, suggesting that cAMP accumulation in response to TSH is not related to structural polarity. In contrast, thyroid follicles cultured without thyroid stimulators showed no significant T3 release in response to TSH, whereas those cultured with TSH or (Bu)2 cAMP showed significant T3 release in response to TSH. These data indicate that in cultured human thyroid follicles, the responses to TSH of cAMP accumulation and T3 release are not always correlated. Among many other explanations, the results were at least compatible with the idea that normal structural polarity is necessary for thyroid hormone release in response to TSH.

Bucladesine↗
PubMed1976

Thyroid iodine uptake, thyroid iodine secretion and plasma TSH levels in male rats during the day and night.

Experiments were performed to assess whether the diurnal changes in thyroid 131I metabolism are paralleled by variations in endogenous iodine. The uptake of iodide by the thyroid gland was determined by a double isotope technique. The T/S iodine ratio and the rate of 131I and 127I secretion from the thyroid gland were determined in rats fed LID during 20 days. The accumulation of iodine by the thyroid gland was prevented by CK1O4 and organic iodine formation was blocked by PTU. The absolute uptake of iodide by the thyroid gland was twice as high during the night than during the day. The thyroid/serum iodide ratios were highest during the night. The rate of release of 131I and 127I from the thyroid gland was augmented in the afternoon. The concentration of TSH in the plasma, measured by radioimmunoassay, was elevated in the afternoon as compared to other times during the day and night. The close association between the diurnal changes in thyroid iodine secretion and plasma TSH concentrations suggest that TSH may be responsible for the differences in iodine secretion observed during the day and night. On the other hand, the intake of iodine in the diet and the urinary clearance of iodine showed diurnal rhythms; the highest values occurred during the night. In addition, about twice as much iodine was available to the thyroid gland at night than during the day. These factors might also contribute to the diurnal variations observed in thyroid iodine metabolism.

Animals↗