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 long-acting thyroid stimulator (LATS) has been thought to be responsible for the hyperthyroidism of Graves's disease. It is detected by its effect on the mouse thyroid gland but cannot be found in all patients with hyperthyroidism. In an attempt to clarify the problem of LATS-negative hyperthyroidism, serum was obtained from untreated patients and its effect in vitro on human thyroid tissue examined, using the activation of adenyl cyclase as a measure of stimulation. Human thyroid adenyl cyclase was activated by both thyroid-stimulating hormone (TSH) and LATS. Thyroid tissue obtained from patients with Graves's disease was relatively less responsive to LATS than was non-toxic thyroid tissue. Of the 24 samples studied five contained LATS and all of these activated adenyl cyclase. The presence of LATS protector in LATS-negative hyperthyroid patients was confirmed but LATS-negative sera had no effect on human thyroid adenyl cyclase activity.
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PMID:Effects of long-acting thyroid stimulator (LATS) and LATS protector on human thyroid adenyl cyclase activity. 474 Apr 44

Thyroid-stimulating antibody (TSAb) is an immunoglobulin G (IgG) occurring in the blood in hyperthyroid Graves' disease patients; it stimulates the thyroid in a manner analogous to the action of TSH, i.e. by activation of adenylate cyclase. Since cholera toxin is also known to stimulate thyroid adenylate cyclase, we studied possible interaction of the enterotoxin on effects of TSAb and TSH using slices of canine thyroid in vitro and an increase in the concentration of cAMP as endpoint. Normal human IgG, known to inhibit the binding of [125I]-iodo-TSH to thyroid membranes, decreased stimulation of thyroid slices by TSH; this inhibitory effect occurred also with preparations of TSAb (inevitably comprised mainly of normal IgG) that were themselves stimulatory. The cholera toxin effect was not prevented by normal IgG and, by factorial analysis of variance, was shown to potentiate the action of subsequently added TSAb or TSH. There was also positive interaction of the effect of TSAb with the combination of TSH and cholera toxin. The data indicate that responses of thyroid tissue to TSAb and TSH are readily influenced by effects of other membrane-active agents (in the present context, normal IgG and cholera toxin).
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PMID:Influences of cholera toxin on thyroid stimulation by thyrotropin and thyroid-stimulating antibody. 610 44

Thyroid stimulating immunoglobulins were measured in 43 patients with Graves' disease both before and at the end of longterm antithyroid treatment. Parallel determinations were performed of thyrotropin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cyclase stimulating antibodies (TSAb). Before treatment 33 patients were TBII positive and 32 TSAb positive, and at the end of treatment 19 remained TBII positive and 14 TSAb positive. The frequency of relapse was about 70% in the positive patients and about 40% in the patients, who became negative in either test for thyroid stimulating immunoglobulins. By combination of the two assays 23 patients were positive in both before treatment. In these patients 5 relapsed of the 6 who remained positive for both, while none relapsed of the 5 patients, who became negative during treatment. In the remaining 12 patients either TBII or TSAb became negative during treatment and 7 of these relapsed. It is concluded, that the combined measurement of TBII and TSAb in this study seemed superior to the separate determinations of either activity in predicting relapse after medical treatment of Graves' disease, though this evaluation was only possible in part of the patients.
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PMID:The prognostic value of parallel measurements of thyrotropin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cyclase stimulating antibodies (TSAb) in Graves' disease after longterm antithyroid treatment. 613 99

To determine whether the beta-blocking drug propranolol had any physiologic effect on normal (n = 14) and adenomatous (n = 15) human thyroid tissues, experiments were performed to study the binding of the beta-blockers 125I-iodocyanopindolol (125I-ICYP) and 125I-iodohydroxybenzylpindolol (125I-IHYP) and the stimulation of adenyl cyclase (AC) by isoproterenol. 125I-ICYP and 125I-IHYP failed to show high-affinity binding in 27 of 29 specimens, whereas two (one normal and one adenomatous) thyroid tissues demonstrated high-affinity binding (Kd 5.5 +/- 1 X 10(-9) M) for 125I-ICYP. Thyroid-stimulating hormone (0.3 IU/ml), guanosine triphosphate (10(-4) M), and Gpp (NH)p(10(-4) M) stimulated AC in all thyroid tissues, although in two tissues (normal) Gpp (NH)p failed to cause a significant increase. Isoproterenol (10(-4) M), in contrast, had no effect on basal AC activity or on guanosine triphosphate, and Gpp (NH) p stimulated AC activity in 26 of the 29 thyroid tissues. In one of the two tissues that increased AC in response to isoproterenol, the beta-blocking drugs propranolol hydrochloride, bunitrolol hydrochloride, and tolilprolol hydrochloride decreased AC stimulation to isoproterenol at concentrations of 10(-6) M (p less than 0.05). Higher concentrations of propranolol (10(-4) - 10(-2) M) decreased AC stimulation to thyroid-stimulating hormone (p less than 0.01), not only in this responsive tissue but also in tissues that failed to demonstrate high-affinity binding for 125I-ICYP and AC stimulation to isoproterenol (p less than 0.01). Thus most normal and adenomatous human thyroid tissues lack beta-receptors and a functioning beta-receptor AC system. High concentrations of propranolol in vitro decreased AC response by thyroid-stimulating hormone, but this is probably a nonreceptor-mediated effect.
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PMID:Absence of high-affinity binding sites for beta-adrenergic blockers and lack of adenyl cyclase stimulation to beta-adrenergic stimulators in most normal and adenomatous human thyroid tissues. 615 May 53

In 50 consecutive patients with Graves' disease treated with PTU, 7 (group 1) developed increasing goitre in spite of unmeasurable TSH. Thyroid variables were compared with those from 10 controls with an ordinary response to PTU (group 2). Serum T4 decreased in group 1 from 246 +/- 47 nmol/l (mean +/- SD) to 40 +/- 9 nmol/l after 6 weeks of PTU treatment and continued to be below the normal range during the next 4 months. In group 2 serum T4 decreased from 190 +/- 35 to 88 +/- 47 nmol/l and stayed in the normal range. Serum T3 was normalized in both groups after 6 weeks but increased to values above the normal range in group 1 after that time. In spite of unmeasurable TSH during the 6 months of treatment in group 1, thyroid volume, determined ultrasonically, increased significantly from 60 +/- 29 to 93 +/- 68 ml (P less than 0.05), but was unaltered in group 2 about 25 ml. Thyroid stimulating antibodies (TSAb) measured by adenylate cyclase activation (normal below 109%) decreased in group 2 from 117 +/- 23 to 90 +/- 17% (P less than 0.01) (6 months of therapy), but increased significantly in group 1, from 201 +/- 47% to a maximum value of 234 +/- 69% (P less than 0.05). TSH binding inhibitory immunoglobulins (TBII) (given as per cent inhibition, normal below 26%) decreased in group 2 from 43 +/- 29 to 29 +/- 27% (P less than 0.05) but were unaltered high in group 1, 66 +/- 25% before therapy and 57 +/- 26% after 6 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thyroid stimulating immunoglobulins in Graves' disease with goitre growth, low thyroxine and increasing triiodothyronine during PTU treatment. 615 28

Increased frequencies of thyroid diseases and thyroid microsomal antibodies have been observed in insulin-dependent diabetes mellitus. However, the exact prevalence of thyroid-stimulating immunoglobulins has not been established. In the present study these antibodies were measured by both a radioreceptor and an adenylate-cyclase stimulation assay. In forty-six patients with insulin-dependent diabetes mellitus without endogeneous insulin production (C-peptide concentration less than or equal to 0.06 nmol 1(-1)) the receptor assay was positive in ten and the stimulation assay in fifteen patients. The immunoglobulins of four patients inhibited the adenylate cyclase, and one of these was positive in the receptor assay. In nine patients with post-prandial C-peptide 0.07-0.19 nmol 1(-1), five had adenylate-cyclase-stimulating antibodies, while none were positive in the receptor assay. Thyroid hormones and thyrotropin concentrations were not different in the forty-six patients without endogenous insulin production with thyroid-stimulating immunoglobulins compared with patients without these antibodies. Patients with thyroid-stimulating immunoglobulins required a daily median amount of 0.71 IE of insulin kg-1 compared to median of 0.57 IE kg-1 in patients without these antibodies (P less than 0.03), despite a similar degree of diabetic regulation. The level of tri-iodothyronine was correlated to the antibody level in patients with adenylate-cyclase-stimulating antibodies. While the prognostic and possibly pathogenetic importance of these antibodies in Graves' disease have been established, their significance in insulin-dependent diabetes mellitus remains to be demonstrated.
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PMID:Thyroid-stimulating immunoglobulins in insulin-dependent diabetes mellitus. 615 3

Thyroid hormone has been shown to accelerate fetal lung development, but the mechanisms by which this hormone acts are yet unknown. Since this hormone may act indirectly by potentiating the action of endogenous catecholamines, we studied this mechanism by measuring beta-adrenergic receptors in fetal lung. Fetal rabbits at 27 days of gestation were treated with triiodothyronine (T3), 100 micrograms/100 g, in the presence and absence of propranolol, 200 micrograms/100 g, or actinomycin D, 20 micrograms/100 g. Fetuses were killed by decapitation either after 4 or 24 h of T3 treatment. The beta-adrenergic antagonist l-[3H]dihydroalprenolol was used to directly estimate the number and affinity of beta-adrenergic receptor in lung membranes. T3 increased the number of beta-adrenergic receptors in fetal lung, but the affinity of binding did not change. The enhancement of binding capacity after 4 h of T3 treatment was not inhibited by actinomycin D. However, 24-h T3-mediated stimulation was partially blocked by actinomycin D. In addition, T3 stimulated the catecholamine content, adenylate cyclase activity, and adenosine 3',5'-cyclic monophosphate content of lung. T3 increased the lecithin-to-sphingomyelin ratio, phosphatidylglycerol, and disaturated phosphatidylcholine content of the pulmonary lavage fluid. These parameters were completely inhibited by propranolol after 4 h and partially inhibited by actinomycin D after 24 h. Thus thyroid hormone enhances lung maturation by increasing the number of beta-adrenergic receptors in fetal lung.
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PMID:Potentiation of surfactant release in fetal lung by thyroid hormone action. 620 83

Sera from a reference pool, 29 controls and 18 patients with Graves' disease were fractionated on sepharose CL-4B protein A. After a primary elution of the unbound fraction at normal pH, IgG subclasses 1, 2 and 4 were eluted using a discontinuous pH gradient. The eluate was monitored by UV-absorption at 280 nm and three peaks were observed within narrow pH ranges in all sera tested. From the reference pool (n = 10) peak A was eluted at pH 6.6 +/- 0.1, peak B at 4.2 +/- 0.03 and peak C at 3.8 +/- 0.01. This distribution was partially related to the IgG subclasses with IgG1 recovered in peak C, while IgG2 and IgG4 were distributed in both peak B and C. Thyroid adenylate cyclase stimulating antibodies (TSAb) and thyrotrophin binding inhibiting immunoglobulins (TBII) were measured in the pooled fractions under these peaks. In the reference pool total assay variations (SD) were 10-22 per cent. The 95 percentiles of the 29 control values were used as reference range. In the 18 patients TSAb were positive in 4 in fraction A, 9 in B and 12 in C. TBII were found in one in fraction A, none in B and 13 in C. No correlation between TSAb and TBII values were found before or after fractionation. In most cases TSAb activity was highest in fraction C, however, in 3 patients fraction A was the more active and in these patients TBII were only found in fraction C. It is concluded, that the present results indicate a heterogeneity of the thyroid stimulating immunoglobulins with separation of the TSAb and TBII activities in some patients.
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PMID:Isolation of thyroid stimulating immunoglobulins by affinity chromatography using protein A sepharose. 623 35

Thyroid hormones are known to influence the noradrenergic neurotransmission in several peripheral organs. In order to find out whether similar changes exist in the central nervous system, we investigated adrenoceptor-mediated responses in the rat brain cortex during propylthiouracil-induced hypothyroidism. In contrast to unchanged basal cAMP levels, the cAMP accumulation following (-)noradrenaline incubation (3 X 10(-6)--3 X 10(-5) M) was significantly reduced in brain slices from hypothyroid animals. The difference between controls and propylthiouracil-fed rats became more pronounced when (-) isoprenaline (3 X 10(-6)--3 X 10(-5) M) was used for selective stimulation of beta-adrenoceptors. Since the cAMP increase mediated via alpha-adrenoceptors was not affected, it may be concluded that thyroid hormone deficiency only impairs the beta-adrenergic transmission. Phosphodiesterase activity remained unaltered suggesting that thyroid hormones influence the beta-adrenoceptors or the adenylate cyclase coupled to it. The sensitivity of presynaptic alpha-adrenoceptors modulating the release of noradrenaline was evaluated using occipital cortical slices preincubated in 3H-noradrenaline. Clonidine inhibited whereas phentolamine enhanced the 3H-overflow induced by electrical stimulation in a dose-dependent manner. No differences could be detected between control- and propylthiouracil-treated animals. Thus presynaptic alpha-adrenoceptors are not affected by hypothyroidism.
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PMID:Effects of thyroid hormone deficiency on pre- and postsynaptic noradrenergic mechanisms in the rat cerebral cortex. 625 Apr 98

The action of thyrotropin (TSH) on plasma membranes was studied to elucidate the mechanism of hormonal regulation of malignant versus normal human thyroid tissue. Thyroid plasma membranes of six specimens of papillary or follicular carcinoma and six of adenoma, as well as adjacent normal tissue obtained from these patients, were evaluated with respect to binding of 125I-labeled TSH and stimulation of adenylate cyclase. Scatchard analysis of TSH binding revealed the presence of two species of binding sites in normal thyroid of different affinities and capacities. In 11 of 12 tumors studied, the high-affinity binding site remained intact; however, the total number of low-affinity sites was markedly lower than normal tissue. Other parameters of binding were not altered in neoplastic thyroid. In each of these tissues, the hormone responsiveness and kinetics of adenylate cyclase activation were essentially identical to those observed in normal tissue, although basal activity was typically greater in the neoplasm. One carcinoma was totally deficient in both 125I-labeled TSH binding and TSH-stimulatable adenylate cyclase, although basal activity was detected. Furthermore, adenylate cyclase of this specimen was not activated by prostaglandin, in contrast to normal thyroid and other thyroid tumors. These results suggest that: (a) clinical behavior of thyroid carcinomas may not be reflected by TSH receptor-adenylate cyclase function; (b) lack of clinical response as manifest by tumor regression cannot be ascribed to the absence of functional TSH receptors or adenylate cyclase; and (c) decreased low-affinity binding present in tumors is not correlated with altered hormone responsiveness of adenylate cyclase but may reflect more general cancer-induced changes in membrane structure or composition.
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PMID:Thyrotropin receptor-adenylate cyclase function in human thyroid neoplasms. 626 64


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