Influence of transforming growth factor beta1 (TGF-beta1) on the behaviour of porcine thyroid epithelial cells in primary culture through thrombospondin-1 synthesis.
(9/2714)
Transforming growth factor beta1 (TGF-beta1) is a secreted polypeptide that is thought to play a major role in the regulation of folliculogenesis and differentiation of thyroid cells. On porcine thyroid follicular cells cultured on plastic substratum, TGF-beta1, in a concentration-dependent way, promoted the disruption of follicles, cell spreading, migration and confluency by a mechanism that did not involve cell proliferation. TGF-beta1 strongly activated the production of thrombospondin-1 and (alpha)vbeta3 integrin in a concentration-dependent manner whereas the expression of thyroglobulin was unaffected. Anisomycin, an inhibitor of protein synthesis, inhibited the effect of TGF-beta1 on cell organization. Thrombospondin-1 reproduced the effect of TGF-beta1. In the presence of thrombospondin-1 cells did not organize in follicle-like structures but, in contrast, spreaded and reached confluency independently of cell proliferation. This effect is suppressed by an RGD-containing peptide. The adhesive properties of thrombospondin-1 for thyroid cells were shown to be mediated by both the amino-terminal heparin-binding domain and the RGD domain of thrombospondin-1. Adhesion was shown to involve (alpha)vbeta3 integrin. The results show that TGF-beta1 exerted an influence upon function and behaviour of follicle cells partly mediated by the synthesis of thrombospondin-1 and of its receptor (alpha)vbeta3 integrin. (+info)
A negative iodine balance is found in healthy neonates compared with neonates with thyroid agenesis.
(10/2714)
We studied the effects of the presence or absence of the thyroid gland on the iodine metabolism and excretion in term Dutch newborns by performing a retrospective study of the urinary iodine excretion in 193 term newborns with abnormal congenital hypothyroidism screening results. Thirty-six euthyroid newborns with decreased thyroxine-binding globulin levels were compared with 157 hypothyroid patients, 54 due to thyroid agenesis and 103 due to thyroid dysgenesis. A significant difference in the urinary iodine excretion was observed between the agenesis group (mean: 28 micrograms/24 h) and the euthyroid newborns (mean: 46 micrograms/24 h, P=0.001). In conclusion, healthy, euthyroid, term newborns excreted more iodine in their urine than newborns with thyroid agenesis. These results strongly indicated the existence of a temporarily negative iodine balance: the excretion of iodine prevailed over the intake and the newborn's thyroidal iodine, stored during pregnancy, could be used for thyroxine synthesis in the postnatal period. Since healthy term neonates were able to maintain adequate plasma free thyroxine concentrations under normal TSH stimulation, the prenatally acquired iodine stores could be considered sufficiently high to compensate for the transient postnatal losses. (+info)
Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone.
(11/2714)
Steroid receptor co-activator 1 (SRC-1) is a transcription co-factor that enhances the hormone-dependent action, mediated by the thyroid hormone (TH) receptor (TR) and other nuclear receptors. In vitro studies have shown that SRC-1 is necessary for the full expression of TH effect. SRC-1 knockout mice (SRC-1(-/-)) provide a model to examine the role of this co-activator on TH action in vivo. At baseline, SRC-1(-/-) mice display resistance to TH (RTH) as evidenced by a 2.5-fold elevation of serum TSH levels, despite a 50% increase in serum free TH levels as compared with wild-type (SRC-1(+/+)) mice. When mice were made hypothyroid, TSH levels increased, obliterating the difference between SRC-1(+/+) and SRC-1(-/-) mice observed at baseline. In contrast, the decline of TSH by treatment with L-triiodothyronine was severely blunted in SRC-1(-/-) mice. These data indicate that SRC-1 is not required for the upregulation of TSH in TH deficiency. However, SRC-1 enhances the sensitivity of TSH downregulation by TH. This is the first demonstration of RTH caused by a deficient co-factor other than TR. It supports the hypothesis that a putative defect in the SRC-1 gene or another co-factor could be the cause of RTH in humans without mutations in the TR genes. (+info)
De Quervain's subacute thyroiditis presenting as a painless solitary thyroid nodule.
(12/2714)
We describe a 39-year-old woman presenting with a painless solitary thyroid nodule, initially without signs suggesting thyroiditis. The serum level of thyrotropin was suppressed whereas those of thyroxine and triiodothyronine were normal. Fine needle aspiration cytology showed no signs of inflammation or malignancy. One week later, the patient felt pain and tenderness on her neck, and erythrocyte sedimentation rate and C-reactive protein were markedly elevated. Thyroid scintigraphy showed a suppressed thyroid pertechnetate uptake. At that time, the diagnosis of subacute thyroiditis was made. Upon treatment with steroids the patient's symptoms as well as the thyroid nodule resolved. This case illustrates that subacute thyroiditis de Quervain may present as a solitary, painless nodule with suppressed thyrotropin and should therefore be considered in the differential diagnosis of such lesions. (+info)
Megalin (gp330) is an endocytic receptor for thyroglobulin on cultured fisher rat thyroid cells.
(13/2714)
We recently reported that megalin (gp330), an endocytic receptor found on the apical surface of thyroid cells, binds thyroglobulin (Tg) with high affinity in solid phase assays. Megalin-bound Tg was releasable by heparin. Here we show that Fisher rat thyroid (FRTL-5) cells, a differentiated rat thyroid cell line, can bind and endocytose Tg via megalin. We first demonstrated that FRTL-5 cells express megalin in a thyroid-stimulating hormone-dependent manner. Evidence of Tg binding to megalin on FRTL-5 cells and on an immortalized rat renal proximal tubule cell line (IRPT cells), was obtained by incubating the cells with 125I-Tg, followed by chemical cross-linking and immunoprecipitation of 125I-Tg with antibodies against megalin. To investigate cell binding further, we developed an assay in which cells were incubated with unlabeled Tg at 4 degrees C, followed by incubation with heparin, which released almost all of the cell-bound Tg into the medium. In solid phase experiments designed to illuminate the mechanism of heparin release, we demonstrated that Tg is a heparin-binding protein, as are several megalin ligands. The amount of Tg released by heparin from FRTL-5 and IRPT cells, measured by enzyme-linked immunosorbent assay (ELISA), was markedly reduced by two megalin competitors, receptor-associated protein (RAP) and 1H2 (monoclonal antibody against megalin), indicating that much of the Tg released by heparin had been bound to megalin ( approximately 60-80%). The amount inhibited by RAP was considered to represent specific binding to megalin, which was saturable and of high affinity (Kd approximately 11.2 nM). Tg endocytosis by FRTL-5 and IRPT cells was demonstrated in experiments in which cells were incubated with unlabeled Tg at 37 degrees C, followed by heparin to remove cell-bound Tg. The amount of Tg internalized (measured by ELISA in the cell lysates) was reduced by RAP and 1H2, indicating that Tg endocytosis is partially mediated by megalin. (+info)
Amiodarone compared with iodine exhibits a potent and persistent inhibitory effect on TSH-stimulated cAMP production in vitro: a possible mechanism to explain amiodarone-induced hypothyroidism.
(14/2714)
Amiodarone (AMD) is a powerful anti-arrhythmic drug used for the treatment of a wide variety of cardiac arrhythmias and its most striking feature is its high iodine content. Thyroid dysfunction is a limiting side-effect of the drug and both AMD-induced hypothyroidism (AIH) and AMD-induced thyrotoxicosis (AIT) are reported. To examine the hypothesis that altered bioavailability of iodine is a contributing event in the pathogenesis of AIH, we compared the effects of AMD and inorganic iodine in vitro on events involved in the process of thyroid autoregulation. FRTL-5 cells and JP26 CHO cells (transfected with the human TSH receptor) were exposed to AMD or NaI in the presence of TSH, and cAMP production was measured as an indicator of cellular function. Forskolin and cholera toxin were also used to determine the possible target sites of AMD and iodide. Our results indicated that there was a difference between the effects of AMD versus those of physiological doses of iodide. The inhibitory effects of AMD occurred at lower concentrations of iodide than those seen in the NaI-treated cells. The effects of AMD were irreversible indicating a possible persistence of the Wolff-Chaikoff effect due to a constant high intracellular iodide level. The inhibitory effects of AMD (also seen at supraphysiological doses of iodide) were partially overcome by forskolin but not by cholera toxin indicating an effect on TSH receptor interactions with the other signal transduction elements such as G proteins and adenylate cyclase. The persistence of the Wolff-Chaikoff effect through loss of autoregulation may be a mechanism of the observed hypothyroidism in some patients taking AMD. The combined effects of the constant release of iodide together with the drug toxicity may be the mechanism for the observed effects. (+info)
Risk of iodine-induced thyrotoxicosis after coronary angiography: an investigation in 788 unselected subjects.
(15/2714)
In this study, the risk of iodine-induced thyrotoxicosis in unselected patients from an iodine-deficient area was investigated. The patients were consecutively enrolled. Thyroid hormone values and urinary iodine excretion were determined before, as well as 1, 4 and 12 weeks after iodine contamination by coronary angiography. Two of 788 unselected patients developed hyperthyroidism within 12 weeks. The two patients did not belong to a risk group for iodine-induced thyrotoxicosis (i.e. old people, patients with goiter or possible thyroid autonomy, low TSH). Both patients had normal TSH levels at baseline and ultrasound of the thyroid was without evidence of nodules. The study shows that in euthyroid unselected patients from an iodine-deficient area short-term iodine contamination by contrast media rarely leads to hyperthyroidism. On account of these facts, prophylactic therapy, e.g. by perchlorate or thiamazole, is not generally recommended, because the risk of side-effects is perhaps even greater than the risk of iodine-induced thyrotoxicosis. (+info)
Biochemical hypothyroidism secondary to iodine deficiency is associated with poor school achievement and cognition in Bangladeshi children.
(16/2714)
Iodine deficiency in pregnancy leads to poor cognitive function in the offspring; however, the effect of concurrent iodine deficiency on school-aged children is not clear. Several studies have shown that school children in iodine-deficient villages have poorer cognitive function than children in iodine-sufficient villages. However, villages differ in many factors that may also detrimentally affect children's development. In addition, the children's nutritional and health status has not usually been taken into account. In this study, we compared the cognitive function and school achievement levels of 170 children who had recently had low thyroxine (T4) levels [T4 /=70 nmol/L (euthyroid)]. The children were matched for school and grade level and came from the same iodine-deficient regions in rural Bangladesh. They were given a battery of cognitive, motor and school achievement tests. We also measured their nutritional status, examined their stools for geohelminths and assessed their home environments. A factor analysis of cognitive and motor function tests yielded two factors, a general cognitive factor and a fine motor factor. The children's height and arm circumference, experience of hunger, parental characteristics and stimulation in the home made independent contributions to their test scores. Controlling for these variables, the hypothyroid children performed worse than the euthyroid children on reading and spelling and the general cognitive factor. These findings indicate that a large number of disadvantages including hypothyroidism are related to the poor development of these children. (+info)