Thyroid hormone-induced stimulation of the sarcoplasmic reticulum Ca(2+) ATPase gene is inhibited by LIF and IL-6.
(25/466)
We investigated the effects of the leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) on 3,3', 5-triiodo-L-thyronine, or thyroid hormone (T(3))-stimulated sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) gene expression on cultured neonatal rat cardiac myocytes. A reduction of T(3) induced increases in SERCA2 mRNA levels after co-treatment with LIF or IL-6. To investigate for the molecular mechanism(s) responsible for the blunted gene expression, a 3.2-kb SERCA2 promoter construct containing a reporter gene was transfected into cardiac myocytes. T(3) treatment stimulated transcriptional activity twofold, whereas co-treatment with T(3) and either of the cytokines caused an inhibition of T(3)-induced SERCA2 transcriptional activity. A T(3)-responsive 0.6-kb SERCA2 construct also showed a similar inhibition by cytokines. Cytokine inhibition of SERCA2 transcriptional activity was also evident when a 0.6-kb SERCA2 mutant, T(3)-unresponsive promoter construct was used. Treatment with T(3) and cytokines showed a significant decrease in transcription when a reporter construct was used that was comprised of direct repeats of SERCA2 thyroid response element I. These data provide evidence for cytokine-mediated inhibitory effects on the SERCA2 promoter that may be mediated by interfering with T(3) action. (+info)
Maturation of proximal straight tubule NaCl transport: role of thyroid hormone.
(26/466)
We have recently demonstrated that the rates of both active and passive proximal straight tubule (PST) NaCl transport in neonatal rabbits were less than in adults. In this segment NaCl entry across the apical membrane is via parallel Na(+)/H(+) and Cl(-)/OH(-) exchangers, which increases in activity with maturation. The present in vitro microperfusion study examined whether thyroid hormone plays a role in the maturational increase in PST NaCl transport. Neonatal and adult PST were perfused with a high-chloride-low bicarbonate solution without organic solutes, simulating late proximal tubule fluid. Thyroid hormone-treated neonates had a higher rate of PST total and passive NaCl transport. In 8-wk-old animals that were hypothyroid since birth, the maturational increase in total and passive NaCl transport was prevented. Thyroid treatment for 4 days in hypothyroid 8-wk-old rabbits increased the rate of both total and passive NaCl transport. The maturational increases in both Na(+)/H(+) and Cl(-)/OH(-) exchange activities were blunted in 8-wk-old hypothyroid animals and increased to control levels with thyroid treatment. This study demonstrates that thyroid hormone is a factor responsible for the maturational increase in both active and passive PST NaCl transport. (+info)
Postnatal handling increases the expression of cAMP-inducible transcription factors in the rat hippocampus: the effects of thyroid hormones and serotonin.
(27/466)
Postnatal handling increases glucocorticoid receptor expression in the rat hippocampus, thus altering the regulation of hypothalamic synthesis of corticotropin-releasing hormone and the hypothalamic-pituitary-adrenal response to stress. The effect on glucocorticoid receptor gene expression represents one mechanism by which the early environment can exert a long-term effect on neural development. The handling effect on hippocampal glucocorticoid receptor expression is dependent on peripheral thyroid hormone release and the activation of ascending serotonergic pathways. In primary hippocampal cell cultures, serotonin (5-HT) increases glucocorticoid receptor expression, and this effect appears to be mediated by increased cAMP levels. In the current studies we examined the in vivo effects of handling on hippocampal cAMP-protein kinase A (PKA) activity. In 7-d-old rat pups, we found that (1) postnatal handling increased adenylyl cyclase activity and hippocampal cAMP levels, (2) the effect of handling on cAMP levels was completely blocked by treatment with either propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, or the 5-HT receptor antagonist, ketanserin, and (3) handling also increased hippocampal PKA activity. We then examined the effects of handling on cAMP-inducible transcription factors. Handling rapidly increased levels of the mRNAs for nerve growth factor-inducible factor A (NGFI-A) (zif268, krox24) and activator protein-2 (AP-2) as well as for NGFI-A and AP-2 immunoreactivity throughout the hippocampus. Finally, we found that the effects of handling on NGFI-A and AP-2 expression were significantly reduced by concurrent treatment with either PTU or ketanserin, effects that paralleled those on cAMP formation. NGFI-A and AP-2 have been implicated in the regulation of glucocorticoid receptor expression during development. Thus, these findings suggest that postnatal handling might alter glucocorticoid receptor gene expression via cAMP-PKA pathways involving the activation of NGFI-A and AP-2. (+info)
Prevalence of positive anti-neutrophil cytoplasmic antibody (ANCA) in patients receiving anti-thyroid medication.
(28/466)
OBJECTIVE: Vasculitis is a rare complication of anti-thyroid medications. There are 32 cases of anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis in association with anti-thyroid medication reported in the English literature. The objectives of this study were to assess the frequency of positive ANCA in patients on long-term anti-thyroid medication, and to follow patients prospectively from commencement of medication to determine whether they became ANCA-positive after therapy. DESIGN: Prospectively collected cross-sectional study of two groups of patients: (i) who had received long-term (>18 months) anti-thyroid medication, and (ii) newly diagnosed thyrotoxicosis before commencement of anti-thyroid medication attending clinic between 28 April 1998 and 30 September 1998. Data were collected for age, sex, ethnicity, underlying thyroid disease, medication and duration, and symptomatology. RESULTS: Eight of 30 patients on long-term anti-thyroid medication (26.7%) were ANCA-positive. All ANCA-positive patients were female, seven were taking propylthiouracil (PTU) at the time of testing. ANCA-positive patients had taken PTU for a mean +/- s.d. of 7.9+/-10.2 years, compared with 0.8+/-2.2 years in ANCA-negative patients (Mann-Whitney, P<0.0001). The ten patients with newly diagnosed thyrotoxicosis were ANCA-negative before commencement of carbimazole. One (10%) became ANCA-positive within 8 months of therapy. CONCLUSIONS: In our population, ANCA-positivity in association with long-term anti-thyroid medication is common (26.7%). One patient who was ANCA-negative prior to anti-thyroid therapy has become ANCA-positive. ANCA should be tested in patients receiving long-term anti-thyroid medications, and in patients with adverse reactions. As PTU is more commonly associated with vasculitis and positive ANCA, carbimazole may be the preferred medication for long-term use. Patients with positive ANCA should be followed, and considered for definitive anti-thyroid therapy, to allow cessation of medication. ANCA-positivity may resolve after cessation of anti-thyroid medication. (+info)
Evidence for co-ordinated changes between vascular endothelial growth factor and nitric oxide synthase III immunoreactivity, the functional status of the thyroid follicles, and the microvascular bed during chronic stimulation by low iodine and propylthiouracyl in old mice.
(29/466)
Vasoactive and angiogenic factors are involved in the autocrine/paracrine thyroid regulation of microvascular bed during goiter development. In the thyroid of old mice, the presence of slowly functioning ('cold') follicles allowed us to study the microvascular regulation of each follicle in correlation with the immunohistochemical expression of vascular endothelial growth factor (VEGF) and nitric oxide synthase III (NOSIII). Mice aged 20 months did or did not receive a goitrogenic treatment (low iodine diet and propylthiouracyl), and their thyroids were processed for light and electron microscopy, and for autoradiography. The relative volumes (Vv) of the capillaries, the number of vessels per follicular area, the mean capillary area and the number of [(3)H]thymidine labeled nuclei were measured separately for 'hot' and 'cold' follicles. Already in control mice, the capillary bed surrounding 'hot' follicles was significantly larger than that seen around 'cold' follicles, because of larger diameters and twice the number of capillaries. This difference persisted whatever the length of the stimulatory treatment. During this treatment, the Vv of the capillaries increased to a larger extent around 'hot' follicles than around 'cold' ones. All vascular changes around 'cold' follicles were less extended and the increase in the capillary diameter was delayed. In control mice, the 'cold' follicles were negative for NOSIII and positive for VEGF while 'hot' follicles were positive for both. During stimulation, all follicles became progressively NOSIII positive. These data support the concept of 'angio-follicular units' in the thyroid and demonstrate their differential regulation in chronic stimulation during which local secretion of VEGF and NO is clearly involved. (+info)
Trends in diagnostic and therapeutic criteria in Graves' disease in the last 10 years.
(30/466)
A questionnaire describing a typical clinical case of Graves' disease and 10 variations on it was mailed to 70 Spanish units of endocrinology with the aim of assessing the new diagnostic and therapeutic trends for hyperthyroidism caused by Graves' disease in Spain and to compare the results obtained from previous studies carried out in Europe and Spain 10 years previously. Responses indicated that thyrotrophin (98%) and free thyroxine (88%) were the most used tests in the in vitro diagnosis of Graves' disease with a significant decrease in the use of total thyroxine, total triiodothyronine, and thyroglobulin in comparison with the surveys conducted 10 years previously in Europe and Spain. The presence of antibodies against the thyrotrophin receptor was the most frequently used immune marker in the diagnosis (78%) and the new use of antithyroperoxidase antibodies (36%) in diagnosis is noteworthy. Antithyroid drugs remain the treatment of choice (98%). Surgery was used mainly for large size goitres (33%) and radioiodine for recurrences after medical (61%) or surgical (80%) treatment. In conclusion, the responses obtained from this questionnaire provide insight into current specialist diagnostic and therapeutic practices with respect to Graves' disease and which could be of value to non-specialist units of endocrinology. (+info)
Maternal hypothyroidism in autoimmune thyroiditis and the prognosis of infants.
(31/466)
We evaluated the developmental prognosis of 31 infants born to mothers with autoimmune thyroiditis. Four of the babies developed transient neonatal hypothyroidism. Their mothers all had low thyroid hormone concentrations during pregnancy. Neonatal thyroid function tended to correlate with maternal thyroid function at delivery in babies born to mothers with Graves'disease who were taking antithyroid drugs. Since severe fetal hypothyroidism sometimes results in neurological damage, it is important to maintain normal maternal thyroid function during pregnancy. (+info)
Thyroid hyperactivity induced by methimazole, spironolactone and phenobarbital in marmosets (Callithrix jacchus): histopathology, plasma thyroid hormone levels and hepatic T4 metabolism.
(32/466)
To determine drug-induced hyperfunction of marmoset thyroids due to inhibition of synthesis or enhancement of metabolic elimination of thyroid hormones, males were orally administered 10 and 30 mg/kg/day methimazole (MMI), 30 and 100 mg/kg/day spironolactone (SPL), or 50 mg/kg/day phenobarbital (PB) for 4 weeks. MMI caused marked hypertrophy of follicular epithelial cells in accordance with a significant decrease in the plasma thyroxin (T4) level. Hypertrophied epithelial cells were filled with dilated rough endoplasmic reticulum and reabsorbed intracellular colloids, and the luminal surface was covered with abundant microvilli. The colloid included vacuoles positive to anti T4 immuno-staining. SPL and PB also caused similar histomorphological changes, although they were less severe than those due to MMI and were not clearly associated with decrease in the plasma T4 levels. Hepatic T4 UDPGT activities tended to increase due to SPL and PB treatment, however, which were not so significant as increases in microsomal cytochrome P-450 contents. Some animals treated with SPL and PB showed marked increases in thyroid weights due to inactive dilated follicles. In conclusion, hyperactivity of thyroid follicles was induced in marmosets not only due to inhibition of T4 synthesis produced by MMI but also because of enhancement of hepatic T4 elimination produced by SPL and PB. However, hypertrophic effects of SPL and PB were less severe than MMI, because plasma T4 levels were maintained at almost pretreatment or control levels after SPL or PB treatment. (+info)