Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction of thyroglobulin (Tg), thyroid-stimulating immunoglobulins (TSI), and TSH on human thyroid plasma membranes from nontoxic goiter was studied in vitro by an adenylate cyclase assay system using human thyroid homogenate. Purified Tg [3 X 10(-10) M (0.2 micrograms/ml) to 3 X 10(-8) M (20 micrograms/ml)] exerted a dose- and time-dependent inhibitory influence on basal adenylate cyclase activity. The inhibition was prevented by preincubation with Tg antibody in excess. Tg (3 X 10(-8) M) caused a significant reduction in the TSH- and TSI-stimulated adenylate cyclase activities, but did not influence stimulation with NaF (8 mM). Fractions of thyroid homogenates were obtained by differential centrifugation, and the maximal inhibitory influence of Tg was located in the 5000 X g fraction. Thus, Tg is an efficient inhibitor of basal and TSH- or TSI- stimulated adenylate cyclase activities, and might be involved in a short loop counterregulation of thyroid adenylate cyclase sensitivity in vivo.
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PMID:Influence of thyroglobulin on basal and stimulated human thyroid adenylate cyclase activity. 611 8

Using a radioreceptor assay and serum immunoglobulin (Ig) prepared by ammonium sulfate precipitation, significant TSH displacement activity (TDA) was demonstrated in 5 of 15 patients with subacute thyroiditis tested during the acute phase. Using a cAMP generation assay, adenyl cyclase stimulation by Ig from patients with subacute thyroiditis was not demonstrated. The nature of the TDA demonstrated in subacute thyroiditis was investigated to determine whether the factor measured was TSH receptor antibody, as is found in Graves' hyperthyroidism, or thyroglobulin, which is know to give false positive responses in the radioreceptor assay. When Ig was prepared by DEAE+-Sephadex chromatography, mean TSH displacement indices were similar to those given by ammonium sulfate-prepared Ig for both Graves' disease and subacute thyroiditis. On the other hand, when Ig was prepared by DEAE+-cellulose chromatography, which isolates highly purified IgG, mean indices were significantly less than for ammonium sulfate-prepared Ig for both Graves' hyperthyroidism and subacute thyroiditis. Thyroglobulin was not detected in Ig prepared by any of the 3 methods. Although high concentrations of crude thyroid-soluble fraction and purified thyroglobulin gave strongly positive responses in the radioreceptor assay, concentrations of thyroglobulin over the range found in the sera of patients with subacute thyroiditis could not be shown to give positive responses. Moreover, TSH displacement indices did not correlate with serum thyroglobulin levels. As determined by species cross-reactivity and dose-responses studies, the TDAs demonstrated in subacute thyroiditis and Graves' hyperthyroidism were similar. It was concluded that the TDA demonstrated in subacute thyroiditis represents antibody which binds to, but does not stimulate, the TSH receptor.
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PMID:Nature of thyrotropin displacement activity in subacute thyroiditis. 627 1

The effect of TSH on the adenylate cyclase-cAMP system and in vitro iodothyronine release, together with the iodothyronine and iodine content of 19s thyroglobulin, were studied in seven clinically euthyroid patients with autonomous thyroid nodules. Basal cAMP and cGMP content together with phosphodiesterase and protein-kinase activities were normal in nodular, and suppressed in extranodular tissue. TSH-dependent cAMP accumulation was reduced in nodular tissue, but normal in the suppressed extranodular tissue. In vitro TSH-dependent iodothyronine release from nodular and extranodular tissue was absent. Thyroxine and iodine content of thyroglobulin extracted from nodular tissue was reduced, while triiodothyronine content was normal but with a low T4/T3 ratio. In extranodular tissue T3, T4 and iodine contents were reduced. In conclusion, autonomous thyroid nodules produced a poorly iodinated thyroglobulin leading to preferential T3 secretion with increased circulating free thyroid hormones even in clinically euthyroid patients.
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PMID:Effects of TSH on cAMP levels and thyroid hormone release in human thyroid 'autonomous' nodules: relationship with iodothyronine and iodine content in thyroglobulin. 629 22

Antibovine thyroid ganglioside antibodies developed in rabbits inhibit thyrotrophin binding to human thyroid plasma membranes. These antibodies are specific for gangliosides as was shown by the liposome agglutination technique. Antiganglioside antibodies did not stimulate basal adenyl cyclase activity in bovine thyroid plasma membranes, but most antiganglioside antibodies inhibit the activity of thyrotrophin stimulated adenyl cyclase. Antiganglioside antibodies react well with bovine thyroid plasma membranes and have considerable cross-reactivity with porcine and human thyroid plasma membranes. Rabbits which develop antiganglioside antibodies after some time have detectable levels of autoantithyroglobulin antibodies in their serum although the preparation used for imminisation did not contain any thyroglobulin or protein material.
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PMID:Influence of antiganglioside antibodies on thyrotrophin binding and adenyl cyclase activity of thyroid plasma membranes. 631 27

The effects of bovine TSH (bTSH) and bovine (bTg) and human thyroglobulin (hTg) on the binding of [125I] bTSH and the activation of adenylate cyclase (AC) were studied in both normal and neoplastic human thyroid homogenates in vitro using adenylate cyclase conditions. [125I]bTSH bound specifically and with high affinity to a particulate fraction from normal thyroid and from benign and malignant thyroid neoplasms; this binding was inhibited by unlabeled bTSH (approximate Kd = 10.0 mU/ml for normal tissue; Kd = 2.5 mU/ml for thyroid neoplasms). Half-maximal activation of AC was obtained at a TSH concentration of approximately 2.5 mU/ml for both normal and neoplastic thyroid tissue, indicating that the high affinity TSH receptors are coupled to AC, at least in the neoplastic thyroid tissue. bTg and hTg did not inhibit [125I]bTSH binding to high affinity TSH receptors in either normal or neoplastic thyroid tissue. bTSH increased AC activity up to 25-fold in neoplastic thyroid tissue and up to 4-fold in normal thyroid tissue, whereas at concentrations up to 1 mg/ml, bTg had no effect. The current study demonstrates that bTSH binds to specific, high affinity receptors and stimulates AC activity in both normal and neoplastic thyroid tissue. bTg and hTg, under the conditions used in this experiment, do not influence TSH binding to its high affinity receptor in these tissues. Since Tg does not influence high affinity TSH binding or AC activity in a particulate fraction rich in plasma membranes from normal or neoplastic thyroid tissue, it is unlikely to have a modulating role on TSH action at the thyroid plasma membrane.
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PMID:Thyrotropin binding and adenylate cyclase activation in normal and neoplastic human thyroid tissue: lack of effect of thyroglobulin. 707 96

Octreotide is a long-acting somatostatin analog that inhibits cell growth and hormone secretion. It has been successfully used in the management of a variety of endocrine tumors (i.e., acromegaly, carcinoid tumors, gastrinomas). In vitro, octreotide suppresses adenylate cyclase activity, DNA synthesis, and cell growth in cultured thyroid cell lines. Previous studies examining the use of octreotide in the treatment of medullary thyroid cancers, in vivo, report symptomatic improvement from tumor-related hormonal hypersecretion; however, octreotide's ability to suppress tumor growth was limited. In the present study, we examine the efficacy of long-term octreotide administration in six subjects with metastatic thyroid carcinoma, including Hurthle cell (one subject), medullary (one subject) and papillary or mixed papillary/follicular cancer (four subjects). All of the subjects had documented recurrences of their thyroid tumors despite appropriate therapy, and were considered to be untreatable by conventional therapeutic modalities (i.e., radioiodine or surgery). Subjects were monitored while receiving relatively high doses (4 mg daily) octreotide subcutaneously for up to 12 months. Octreotide therapy was very well tolerated; mild gastrointestinal symptoms persisted throughout treatment in one subject. Octreotide did not significantly decrease tumor markers (e.g., thyroglobulin, calcitonin, carcinoembryonic antigen). The carcinomas progressed during treatment, as evidenced by an increase in the size and/or number of metastatic lesions. In summary, in this small series subcutaneous octreotide administration did not appear to be efficacious in the management of advanced thyroid cancers.
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PMID:Octreotide therapy in advanced thyroid cancer. 771 6

Thyrotropin (TSH) suppression therapy using thyroid hormone plays an important role in the management of patients thyroidectomized for differentiated thyroid cancer. The rationale for TSH suppression is that differentiated thyroid cancer cells have TSH receptors and show increased adenylate cyclase activity following TSH exposure. L-thyroxine is used for long-term therapy. L-triiodothyronine is preferred when suppressive therapy must be discontinued for radioiodine scan, since its shorter half-life allows more rapid increases of TSH levels. The assessment of TSH suppression is still uncertain. The development of second and third TSH assay generations with progressive improvement in sensitivity has made the TRH test unnecessary and has raised the issue of the TSH level indicative of TSH suppression. In clinical practice TSH values below 0.1 mU/L are considered compatible with appropriate TSH suppression. Serum thyroglobulin is a reliable marker of metastatic disease after total surgical and radioiodine ablation of the thyroid gland and it is useful in the surveillance of patients with differentiated thyroid cancer.
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PMID:[Hormonal therapy in differentiated carcinoma of the thyroid gland]. 788 45

The [3H]thymidine incorporation assay in FRTL-5 cells was used to measure thyroid growth-stimulating antibody in the purified immunoglobulin G (IgG) fraction of patients with endemic nontoxic goiter (grade I-III) living in Italy (n = 34) or Peru (n = 37). IgG of euthyroid nongoitrous subjects living in the same endemic area (n = 25) and from an area of sufficient iodine intake were used as controls. Bovine TSH (10 mU/L) and thyroid-stimulating antibody of Graves' disease produced a significant increase in [3H]thymidine incorporation and DNA content in FRTL-5 cells. IgG from Italian or Peruvian patients with endemic goiter produced a small increase in [3H]thymidine incorporation in FRTL-5 cells (131 +/- 54% and 165 +/- 57%, respectively), which was indistinguishable from that obtained with IgG from normal nongoitrous subjects residing in endemic or nonendemic areas (167 +/- 80% and 161 +/- 36%, respectively). For comparison 18 of 25 (72%) IgG of hyperthyroid patients with Graves' disease produced clear-cut increases in [3H]thymidine incorporation (1142 +/- 1065%) and DNA content (219%) in FRTL-5 cells. IgG from patients with endemic goiter, at variance with Graves' IgG, did not cause an increase in DNA in FRTL-5 cells. All Graves' IgG that stimulated [3H]thymidine incorporation in FRTL-5 cells also stimulated cAMP production in this culture system, whereas no adenylate cyclase stimulation was produced by IgG from patients with endemic goiter. The prevalence of thyroglobulin antibody and thyroperoxidase antibody in endemic goiter patients did not differ from that in control subjects residing in the same iodine-deficient area. Our data show that sera of endemic goiter patients are devoid of thyroid growth-stimulating antibody and thyroid-stimulating antibody activities. These observations argue against a direct role of thyroid autoimmunity in the development of goiter in iodine-deficient areas.
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PMID:Failure to detect thyroid growth-promoting activity in immunoglobulin G of patients with endemic goiter. 790 15

The role of TSH and its receptor in controlling growth of thyroid carcinomas is far from well understood. In order to study this subject further we established a new human thyroid carcinoma cell line. We transfected human thyroid carcinoma cells lacking an endogenous TSH receptor with the human TSH receptor cDNA. Transfected cells, designated HTC-TSHr, expressed the TSH receptor mRNA and synthesized a functional TSH receptor with a TSH binding affinity in the order of magnitude of normal thyroid cells. In response to TSH stimulation HTC-TSHr cells accumulated cAMP, indicating a functional TSH receptor-adenylate cyclase system. However, HTC-TSHr cells did not concentrate iodide and lacked thyroglobulin immunoreactivity, although they did express low amounts of thyroglobulin mRNA. Proliferation of HTC-TSHr cells was inhibited by dibutyryl-cAMP and forskolin and also by TSH via the re-expressed TSH receptor.
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PMID:Expression of the human TSH receptor in a human thyroid carcinoma cell line that lacks an endogenous TSH receptor: growth inhibition by cAMP. 838 51

An in vitro system of secondary cultures of human thyroid follicular epithelial cells in monolayer is described. The 72-h influence of serum and six supplements (thyrotropin, insulin, somatostatin, transferrin, hydrocortisone, glycyl-histidyl-lysine acetate) on growth and function in presence of 3-isobutyl-L-methyl-xanthine (IBMX) was investigated. The function of the cells was evaluated by production of the second messenger adenylate cyclase (cAMP) and the end product thyroglobulin (Tg). Growth was measured as the 3H-thymidine uptake of the cells. Three days of TSH-depletion preceeded the experiments. In presence of IBMX TSH stimulated cAMP production, while stimulation of Tg was only present in some cultures. In absence of IBMX TSH always stimulated the Tg production. The stimulation was independent of the presence of the other five investigated nutritional factors in physiological concentrations. TSH in concentrations from 0.1-10 U/1 stimulated the 72ih 3H-thymidine uptake of the cells. The TSH-stimulated production of Tg and cAMP decreased significantly with increasing concentrations of fetal calf serum (0-10%), (tau = 0.49, P < 0.001, n = 6-29 and tau = 0.75, P < 0.001, n = 6-29, respectively). Thus, serum as a complex, variable and not fully characterized mixture of hormones and growth factors was crucial to the attachment of the cells to the substrate, but inhibited differentiated functions of the human thyroid cells.
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PMID:Human thyroid epithelial cells cultured in monolayers. II. Influence of serum on thyroglobulin and cAMP production. 864 17


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