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)

In a previous paper, we demonstrated that the acute administration of excess iodide inhibits the adenylate cyclase-cAMP system in mouse thyroid lobes. In the present study, we examined whether presurgical therapy with stable iodide reduces the responsiveness to TSH in thyroid tissues from patients with Graves' disease. Eight patients with Graves' disease were presurgically treated with methimazole and stable iodide and six were given methimazole alone. Normal tissues from five patients with thyroid nodules were also tested. We have found that stimulation by TSH (5 and 50 mU/ml) of cAMP formation in thyroid slices from patients preoperatively treated with methimazole and iodide is significantly less than in slices from patients treated with methimazole alone. Similar observations were also made with other thyroid stimulators, such as prostaglandin E2 and 4-methylhistamine. Furthermore, thyroid slices from patients treated with methimazole alone responded to TSH to the same degree as slices of normal tissues. The data suggest that one of the reasons for the hyporesponsiveness to TSH in thyroids from patients with Graves' disease is preoperative treatment with stable iodide.
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PMID:Altered responsiveness to thyrotropin in thyroid slices of Graves' disease preoperatively treated with excess iodide. 23 71

Effects of TSH on the adenylate cyclase-cAMP system and some parameters of intermediary metabolism were investigated in human thyroid carcinoma and adjacent normal thyroid tissue. Basal adenylate cyclase activity and cAMP concentrations were significantly higher in carcinomatous tissue. Basal [1-14C]glucose oxidation, 32Pi incorporation into phospholipids, and organification of iodide were similar in both tissues. Stimulation of cAMP by TSH was significantly greater in normal compared to carcinomatous tissue. In neither tissue was there a good correlation between TSH stimulation of adenylate cyclase activity and cAMP concentrations. The TSH stimulation of 32Pi incorporation into phospholipids by TSH was significantly greater in normal tissue. The mean effect of TSH on iodide organification and glucose oxidation was similar in normal and carcinomatous tissue. Although specific binding of TSH was demonstrated in both normal and carcinomatous tissue, it did not correlate very well with stimulation of adenylate cyclase activity. Hormones other than TSH also augmented adenylate cyclase activity in two of the carcinomas. In individual patients, the relative responsivity of carcinomatous tissue compared to normal was not always consistent when all of the metabolic parameters were considered.
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PMID:Effects of thyroid-stimulating hormone on human thyroid carcinoma and adjacent normal tissue. 23 88

Unlike in all other thyroid preparations, exposure of dog thyroid cells in long-term monolayer culture to iodide (10(-7) to 10(-3) M for up to 19 h did not blunt the subsequent adenosine 3', 5'-cyclic monophosphate (cAMP) response to thyrotropin (TSH) stimulation. This lack of effect of iodide was observed even when confluent thyroid cells were "follicularized" by the action of TSH in the culture medium. Preincubation of these cells in thyroxine (T4) and triiodothyronine (T3) was similarly without effect on the subsequent cAMP response to TSH. Study of thyroid cells during the early phase of primary culture demonstrated that inhibition by iodide (10(-4) M) of the cAMP response to TSH occurred after 7 h but was lost after 48 h of cell culture. This inhibitory effect of iodide was prevented by the inclusion of methimazole in the preincubation medium. As with iodide-insensitive cells, T4 and T3 were without effect on the cAMP response to TSH in iodide-sensitive thyroid cells. Exposure of iodide-insensitive thyroid cells to iodide-containing medium obtained after 2 h of incubation with dog thyroid slices, as well as to medium enriched with the 100,000 g supernatant fraction of homogenates prepared from these thyroid slices, did not restore the inhibitory action of iodide. However, iodide-sensitivity of the cAMP response to TSH was restored by preincubation of iodide-insensitive cells in 10(-4) M iodide plus an H2O2-generating system (glucose-glucose oxidase). These data suggest that T4 and T3 are not organic iodine inhibitors of the thyroid cAMP response to TSH. In addition, they provide evidence against the existence of a soluble, freely diffusible, organic iodine inhibitor of thyroid adenylate cyclase. The loss of sensitivity to iodide inhibition of adenylate cyclase that occurs in thyroid cells shortly after initiation of primary culture appears to be related to a defect in the cellular organification mechanism, possibly the H2O2-generating system.
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PMID:Cultured thyroid cell adenosine 3',5'-cyclic monophosphate response to thyrotropin: loss and restoration of sensitivity to iodide inhibition. 23 22

Adenylate cyclase activity in human thyroid homogenates was studied after stimulation with thyrotropin (TSH) and thyroid stimulating antibodies (TSAb). The results show: 1) TSAb prepared from different patients with Graves' disease show different adenylate cyclase activation patterns and a lag phase is frequently observed. 2) TSH and TSAb appear to cause mutually inhibitory activation of thyroid adenylate cyclase. 3] The maximal adenylate cyclase activation is higher with TSH than with TSAb, but this could possibly be due to contamination of TSAb preparations with an adenylate cyclase inhibitor. 4) There is no absolute copurification of TSH sensitive and TSAb sensitive adenylate cyclase in various subcellular fractions of thyroid homogenate. 5) Incubation of thyroid homogenate with cortisol cause a dose dependent decrease in the adenylate cyclase response to TSAb whereas the response to TSH is either increased or unchanged. The results indicate that TSH and TSAb activate thyroid adenylate cyclase through different pathways in the plasma membrane.
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PMID:TSH and thyroid stimulating antibodies (TSAb) activate thyroid adenylate cyclase through different pathways. 28 12

Thyrotropin (TSH)- and sodium fluoride (NaF)-sensitive adenylate cyclase (AC) activity was measured in ten cases of "cold" thyroid nodules and compared with perinodular tissue. Findings were correlated with the ultrastructure of the nodular and perinodular tissue. Comparisons of the results of assay studies revealed an increase of basal and NaF- and TSH-stimulated AC activity in cold lesions. There was no dissociation of NaF- and TSH-sensitive AC. Ultrastructural findings disclosed a lack of correlation between elevated AC activity and the expected organelle profile indicative of stimulation. Since organelle modulations that are associated with increased protein synthesis were not observed in the face of increased AC activity, an unknown intracellular defect may exist in the expression of the AC-cyclic AMP (adenosine 3':5'-cyclic phosphate) system in cold thyroid nodules.
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PMID:Secretion and adenylate cyclase in thyroid nodules. 58 Aug 72

Basal adenylate cyclase activity of thyroid plasma membranes obtained from six patients with Graves' disease was slightly but not significantly lower than normal (83.3 +/- 13.9 pmol cAMP/10 min/mg of protein versus 120.9 +/- 19.5 pmol cAMP/10 min/mg of protein). In five of these patients the adenylate cyclase activity was stimulated by bovine TSH with an apparent Km value similar to that of normal thyroid (3.1 +/- 0.5 X 10-9 M versus 3.4 +/- 0.6 X 10-9 M). The response to prostaglandin E2 was also normal. In the sixth patient adenylate cyclase activity was stimulated by prostaglandin E2 but not by bovine TSH. The distribution of basal adenylate cyclase activity in various gradient layers was studied in two TSH-responsive patients. A relative increase of this activity was found in the denser layer when compared to normal thyroid tissue. This could be the expression of an altered ratio between the protein and lipid components of the plasma membranes in patients with Graves' disease.
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PMID:TSH-responsive adenylate cyclase activity in thyroid tissue from patients with Graves' disease. 58 26

The occurrence of serum immunoglobulins with capacity to stimulate thyroid adenylate cyclase (TSAb) was studied in seventy-two healthy volunteers and 120 unselected patients with various thyroid diseases. A high frequency of TSAb (82.5%, P less than 0.00006) was found in Graves' disease, while TSAb was present only in 13--20% of serum from patients with nontoxic nodular goitre, nontoxic diffuse goitre, toxic adenoma, toxic nodular goitre and myxoedema. These patients had low level of TSAb compared to patients with Graves' disease. In patients with Graves' disease there was no correlation between the level of TSAb and hormonal status except serum triiodothyronine (rs = 0.29, P less than 0.05), and no relation with eye involvement or presence of microsomal thyroid antibodies was found. The results indicate that the human thyroid adenylate cyclase assay system with 1 hour incubation periods is a sensitive method for detection of immunoglobulins with TSH-like capacity to stimulate the thyroid gland.
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PMID:Thyroid adenylate cyclase stimulating immunoglobulins in thyroid diseases. 58 61

To characterize further the nature and site of the receptor for the IgG stimulator in Graves' disease, we have developed a preparative scheme to provide a bovine thyroid subfraction rich in plasma membranes. Pellets (800 X g) obtained from bovine thyroid homogenates were layered on a 30-64% continuous sucrose gradient (SG). The centrifuged gradient was divided into four portions (SG1, 2, 3, and 4); and these along with the 800 X g pellet were characterized in terms of their capacity to neutralize (bind) the biological activity of LATS, their specific binding of [125I]TSH, and their subcellular marker content. Subfraction SG1 contained the highest adenyl cyclase specific activity, the highest [125I]TSH binding specific activity, and vied with the 800 X g pellet and SG3 for the highest specific activity of LATS neutralization. Electron microscopy of SG1 showed a predominance of plasma membrane structures contaminated with a modest amount of cellular debris. Adenyl cyclase activity in SG1 was enhanced by TSH, LATS, and sodium fluoride. Although a dose-response curve could be established for TSH, a similar relationship could not be established for LATS. We conclude that activation of plasma membrane-bound adenyl cyclase is associated with neutralization of the biological activity of LATS. Further, the difference between [125I]TSH binding and LATS neutralization activity observed in the various thyroid membrane subfractions suggests that either LATS and TSH interact at different sites or have different mechanisms of binding at a common site.
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PMID:The subcellular localization of the long-acting thyroid stimulator inhibitor in bovine thyroid gland. 74 82

Using a simple and reliable assay technique in which the actuel amount of cyclic AMP generated during incubation is determined by competitive protein binding assay, adenylate cyclase activity was measured in 7 cold nodules and 3 samples of normal thyroid tissue. Mitochondrial fraction prepared from surgically obtained tissues was used as the source of the enzyme. We observed an increased adenylate cyclase activity in cold nodules as compared to normal. More importantly, this activity was much more responsive to TSH in cold nodules than in normal (maximal stimulation: 1050+/-200% vs 320+/-120%). Also, maximal TSH stimulation was similar to that elucited by fluoride in the cold nodules but only one-third in normal tissue. These results suggest that higher efficiency of TSH in cold nodules may be related to increased TSH binding or coupling of TSH receptors with the caralytic subunit of adenylate cyclase.
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PMID:[Comparison of the effect of TSH and fluoride on the adenylate cyclase activity of cold thyroid nodules (author's transl)]. 100 7

131I-TSH prepared by the lactoperoxidase method was used to study the binding of hormone to bovine thyroid plasma membrane. Specific binding was obtained using as little as 0.12 mU/ml 131I-TSH. Half-maximal binding occurred with 17.1 plus or minus 3.5 mU/ml and saturation at approximately 40 mU/ml. Scatchard plot analysis revealed two classes of binding sites, with association constants of 1.1 plus or minus 0.06 x 10(8) M(-1) and 1.4 x 10(7) M(-1) for the high- and low-affinity sites, respectively. Binding of 131I-TSH was linearly related to the amount of thyroid plasma membrane protein. Other polypeptide hormones and prostaglandin E1 did not inhibit specific TSH binding. Identical results were obtained using two TSH preparations of different biologic specific activity. 12.5 mU/ml unlabeled TSH decreased 131I-TSH binding 50%, and 156 mU/ml caused complete inhibition. After equilibrium of 131I-TSH binding was established, maximal displacement was achieved by 120 min using about 300 mU/ml TSH. However, only about one-half of the 131I-TSH was displaced. Although GTP potentiated the stimulation of adenylate cyclase by TSH, it inhibited binding of 131I-TSH. Binding of TSH correlated very well with activation of adenylate cyclase.
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PMID:Studies of thyroid-stimulating hormone binding to bovine thyroid plasma membranes. 114 91


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