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)

Thyroid hormone regulation of beta-adrenergic receptor-coupled adenylate cyclase activity was studied in rat liver and heart particulate fractions. Thyroidectomy (Tx) increased isoproterenol-stimulated cAMP accumulation in the liver and decreased it in the heart. Administration of L-thyroxine (L-T4) or L-3,3',5-triiodothyronine (L-T3) reversed these changes in both liver and heart. The changes observed in liver beta-receptor-coupled adenylate cyclase activity after Tx were similar to those reported after adrenalectomy (ADX). Thus the hypothesis was considered that these changes with altered thyroid status are produced indirectly through alteration in adrenal corticosteroids. Hydrocortisone in Tx rats decreased liver isoproterenol-stimulated adenylate cyclase activity but had no significant effect on the heart. Serum corticosterone levels were decreased significantly (by 34%) in Tx rats, as compared to euthyroid rats. Administration of L-T4 to Tx rats doubled the serum corticosterone levels. In Tx-ADX rats, L-T4 had no significant effect on liver beta-receptor-coupled adenylate cyclase. However, L-T4 significantly increased heart beta-receptor-coupled adenylate cyclase in these animals. Dexamethasone, but not deoxycorticosterone, decreased liver isoproterenol-stimulated cAMP accumulation in Tx animals to the same extent as was observed with L-T4 and hydrocortisone. Thus overall the results indicate that in the liver, as opposed to the heart, thyroid hormones regulate beta-adrenergic receptor-coupled adenylate cyclase indirectly through corticosteroids. Glucocorticoid rather than mineralocorticoid activity seems to be responsible for this regulation.
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PMID:Differential regulation of beta-adrenergic receptor-coupled adenylate cyclase by thyroid hormones in rat liver and heart: possible role of corticosteroids. 282 Aug 55

Thyroid hormones exert a permissive influence on the ability of cells to respond to other hormones. In hypothyroidism, stimulation of adenylate cyclase by beta-adrenergic agonists is impaired in rat fat cells, whereas inhibition by adenosine is potentiated. The effects of thyroid status on steady-state levels of the G-protein subunits alpha-Go, alpha-Gi, and beta-G35/36 were investigated using specific antibodies and quantitative immunoblotting of rat fat cell membranes. The amount of alpha-Go (Mr 39,000, alpha-G39) detected in fat cell membranes of euthyroid rats was 44 +/- 5 pmol/mg of membrane protein (n = 5). In the hypothyroid state, the amount of the alpha-subunits of Gi (Mr 41,000, alpha-G41) and Go were found to be markedly increased in comparison to the control. The steady-state level of alpha-G41 and alpha-G39 increased more than 50 and 70%, respectively, in the hypothyroid state. The beta-subunit of G-proteins of rat fat cells appears as a doublet of proteins with Mr = 35,000/36,000 on sodium dodecyl sulfate-polyacrylamide gels. The amount of beta-G35/36 detected in fat cell membranes of euthyroid rats was 0.20 +/- 0.03 nmol/mg of protein (n = 5) and was found to increase by about 60% in the hypothyroid state. Administration of triiodothyronine in vivo (short term hyperthyroidism) resulted in a decrease in the amounts of alpha-G41 and alpha-G39 subunits (25 and 20%, respectively). In contrast to these effects of thyroid hormones on Go and Gi, the steady-state level of beta-adrenergic receptors was not significantly altered by changes in thyroid status. Thus, thyroid status in vivo can modulate the steady-state levels of specific G-proteins.
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PMID:Steady-state levels of G-proteins and beta-adrenergic receptors in rat fat cells. Permissive effects of thyroid hormones. 283 Dec 28

Several adrenergic effectors and neurotransmitters were tested as potential regulators of myelin basic protein (MBP) and histone methyltransferase activities. Both enzymes were specifically activated by beta-adrenergic agonists in a stereospecific manner. Cyclic AMP (but not AMP) stimulated the enzymes to the same extent as did the beta-adrenergic agonist, (-) isoproterenol. The studies suggest that beta-adrenergic agonists stimulate adenylate cyclase thereby causing an increased production of cyclic AMP which stimulates the methyltransferases. Cycloheximide addition to the reaction mixture did not affect the stimulation due to cyclic AMP, indicating that new protein synthesis is not involved in the cyclic AMP stimulation of the methyltransferases. Thyroid hormone (T3) has been shown to stimulate MBP methyltransferase [Amur et al, 1984] and could exert its stimulatory effect through beta-adrenergic-dependent systems. But the beta-adrenergic antagonist, propranolol, did not block the stimulation by T3, suggesting that the effect of T3 is not mediated through beta-adrenergic-dependent systems. Thus, the methylation of MBP seems to be regulated both by T3 and by neurotransmitters and/or hormones mediating their effects through cyclic AMP production, whereas the methylation of histones seems to be regulated only by the latter.
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PMID:Beta-adrenergic stimulation of protein (arginine) methyltransferase activity in cultured cerebral cells from embryonic mice. 287 8

The regulation of TSH biological activity by thyroid hormone and TRH was studied by comparison of pituitary and in vitro secreted TSH from normal and thyroidectomized rats that were alternatively treated with TRH either in vivo or in vitro. Normal and thyroidectomized (3 weeks postthyroidectomy), rats were injected with saline or TRH (100 micrograms) three times over 24 h. Pituitaries were incubated in vitro for 6 h, and six groups of samples from both pituitary and secreted TSH were analyzed: normal (n = 6), thyroidectomized (n = 6), normal and thyroidectomized groups treated with TRH in vitro (n = 2 each) with 10(-8) M TRH added to the incubation medium, and normal and thyroidectomized groups TRH treated in vivo, their incubation medium also supplemented with 10(-8) M TRH (n = 4 each). The biological activity of TSH in pituitary extracts and media was analyzed in terms of the ability to stimulate adenylate cyclase in human thyroid membranes. Thyroidectomy significantly decreased pituitary TSH bioactivity (70%) compared to normal, with no effect on secreted TSH in the medium. TRH, both in vivo and in vitro, when compared to the corresponding untreated groups, produced a significant increase in bioactive TSH in media from both normal (TRH in vivo, 131%; TRH in vitro, 139%) and thyroidectomized samples after TRH in vivo (158%). The TRH effect in the pituitary showed a significant increase in TSH bioactivity from normal samples treated with TRH in vivo (137%), whereas in thyroidectomized pituitary samples with TRH in vitro, TSH bioactivity was decreased (69%). These results indicate that thyroid hormone deficiency and TRH differentially regulate TSH bioactivity. Thyroid hormone deficiency induced a decrease in pituitary TSH bioactivity and favored the effect of TRH on secretion of more bioactive forms. TRH not only induced the formation of more bioactive forms but also stimulated their secretion into the medium.
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PMID:Regulation of thyrotropin (TSH) bioactivity by TSH-releasing hormone and thyroid hormone. 308 13

Thyroid function was studied in 17 unrelated patients with Pendred's syndrome. Fourteen patients had been treated with L-thyroxine, which was withdrawn during the investigation. Eight of the patients had previously had a thyroid resection. Thirteen patients had goiter at the time of study. The serum total thyroxine and serum total triiodothyronine concentrations were normal in 8, of whom 3 had elevated serum TSH concentrations. In the remaining 9 cases the thyroxine levels were below normal with elevated TSH. Serum reverse triiodothyronine concentrations were decreased in 8 out of 11. Median serum thyroglobulin was 973 micrograms/l (range 10.9-3200 micrograms/l) and increased in 13. Three patients had slightly positive thyroglobulin antibodies and one with normal level was thyrodectomized. Thyroid stimulating antibodies as measured by adenylate cyclase stimulation (median 114%, range 85-137%) were slightly increased in 11. When measured as TSH binding inhibiting immunoglobulins none were positive. Thyroid microsomal antibodies were negative in all. All patients with a detectable 131I uptake (n = 15) showed a pathological iodide perchlorate discharge test (median 32%, range 16-46%). These findings indicate an organification defect with impaired hormone synthesis.
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PMID:Thyroid function in patients with Pendred's syndrome. 336 Oct 85

A technique for in vivo infusion in the superior thyroid artery in rats and mice was developed and evaluated. The influx catheter is inserted in retrograde direction into the superior carotid artery. The infusate mixed with blood is directed exclusively to the thyroid lobe via the superior thyroid artery. The thyroid isthmus is divided and the other lobe serves as a control. Thyroid ultrastructure was unaltered after infusion for at least 4 h and the follicle cells displayed a normal morphological response to TSH. Electron microscopical autoradiography (125I, [3H]leucine) was performed using 20-80 times less label as compared with iv administration. Infusion of forskolin, a stimulator of adenylate cyclase, increased the intrathyroidal cyclic AMP levels about 10-fold. Infusion of the ionophore monensin yielded typical dilations of Golgi cisternae as well as reduced secretion of newly synthesized protein into the follicle lumen. The arterial infusion technique developed is useful when in vitro methods or systemic administration of substances are unsuitable. The technique permits selective administration of small amounts of experimental substances to the thyroid in high concentrations.
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PMID:A method for selective infusion in the thyroid artery of the rat and mouse. 341 18

Thyroid-stimulating hormone (TSH) has been shown to stimulate mitosis in cultures of the continuous thyroid cell strain FRTL-5, and this system may be used to quantify the growth-promoting effects of thyroid stimulators. Removal of TSH from the culture medium led to a progressive decline in the metaphase index (MI) to zero, after 7 days. Thus the cell culture conditions may be manipulated so that metaphases are absent in control cultures, i.e. in the absence of TSH. Restimulation with TSH caused an increase in mitosis only after a lag-phase of 20-24 h. A maximum MI was observed between 40 and 50 h, with a secondary peak between 70 and 75 h. An immunoglobulin G (IgG) preparation from a thyrotoxic patient with a small goitre which was a potent stimulator of adenylate cyclase in these cells produced a similar time-course. A dose-response relationship to TSH was obtained 47 h after addition of the hormone. Significant stimulation was observed with 10 mu. TSH/l, and maximal stimulation with 1 unit TSH/l; the highest dose tested (10 units TSH/1) slightly decreased the MI below the maximum. Stimulation of these cells appeared to be TSH specific, since FSH, human chorionic gonadotrophin, LH and isoproterenol did not induce mitosis. Epidermal growth factor under the experimental conditions employed was unable to induce mitosis. However, an increase in mitosis was observed with the adenylate cyclase stimulator forskolin. These experiments confirm the mitogenic properties of TSH and we describe a metaphase index assay for the detection of thyroid growth promotors.
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PMID:Thyrotrophin stimulation of mitogenesis of the rat thyroid cell strain FRTL-5: a metaphase index assay for the detection of thyroid growth stimulators. 404 May 48

Thyroid-stimulating hormone increased the cyclic 3',5'-adenosine monophosphate concentration in dog thyroid slices during a 1-minute incubation period and produced a maximum effect soon thereafter. The elevation persisted for at least 30 minutes. The concentrations of the cyclic 3',5'-adenosine monophosphate increased as the TSH concentration was increased from 0.125 to 50 milliunits per milliliter. Prostaglandin E(1), which increases glucose oxidation in dog thyroid slices, also increased the concentration of cyclic 3',5'-adenosine monophosphate. Although sodium fluoride stimulates thyroid adenyl cyclase, it did not increase concentration of cyclic 3',5'-adenosine monophosphate. Carbamylcholine and menadiol sodium diphosphate augment glucose oxidation in dog thyroid slices but do not change concentrations of cyclic 3',5'-adenosine monophosphate.
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PMID:Thyroid-stimulating hormone and prostaglandin E1 stimulation of cyclic 3',5'-adenosine monophosphate in thyroid slices. 430 65

Benign and malignant nodules in human thyroid glands, which did not concentrate iodide in vivo, were also unable to accumulate iodide in vitro. The mean thyroid-to-medium ratio (T/M) in seven benign nodules was 0.8+/-0.2 compared with 7+/-2 in adjacent normal thyroid tissue. In four malignant thyroid nodules, the mean T/M was 0.5+/-0.1 compared with 11+/-4 in adjacent normal thyroid. Despite the inability of such nodules to concentrate iodide, iodide organification was present but was only one-half to one-third as active as in surrounding normal thyroid. Thyroid-stimulating hormone (TSH) increased iodide organification equally in both benign nodules and normal thyroid although it had no effect in three of the four malignant lesions. The reduction in organification is probably related to the absence of iodide transport, since incubation of normal thyroid slices with perchlorate caused similar diminution in iodide incorporation but no change in the response to TSH. Monoiodotyrosine (MIT) and di-iodotyrosine (DIT) accounted for most of the organic iodide in both the nodules and normal tissue. The MIT/DIT ratio was similar in normal and nodule tissue. The normal tissue contained much more inorganic iodide than the nodules, consistent with the absence of the iodide trap in the latter tissue. The thyroxine content of normal thyroid was 149+/-17 mug/g wet wt and 18+/-4 mug/g wet wt in the nodules. The transport defect in the nodules was not associated with any reduction in total, Na(+)-K(+)- or Mg(++)-activated ATPase activities or the concentration of ATP. Basal adenylate cyclase was higher in nodules than normal tissue. Although there was no difference between benign and malignant nodules, the response of adenylate cyclase to TSH was greater in the benign lesions. These studies demonstrate that nonfunctioning thyroid nodules, both benign and malignant, have a specific defect in iodide transport that accounts for their failure to accumulate radioactive iodide in vivo. In benign nodules, iodide organification was increased by TSH while no such effect was found in three of four malignant lesions, suggesting additional biochemical defects in thyroid carcinomas.
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PMID:Demonstration of iodide transport defect but normal iodide organification in nonfunctioning nodules of human thyroid glands. 435 98

We have shown that two unrelated prostaglandin antagonists block both thyrotropin (TSH) and prostaglandins E (PGE(1), PGE(2)) stimulation of thyroidal adenyl cyclase activation and cyclic 3',5'-adenosine monophosphate (cAMP) formation, suggesting that prostaglandins play an important role in regulating thyroid function. To further explore this postulate, we measured prostaglandin content by radioimmunoassay in homogeneous bovine thyroid cell preparations in the presence and absence of TSH. Antibodies to albumin-conjugated PGE(1) and PGF(2alpha) showed specificity for prostaglandins E and F, respectively, but reacted, albeit far less effectively, with heterologous prostaglandins. A double antibody system was used to separate free from antibody-bound PGE(1)-(3)H and PGF(2alpha)-(3)H. Thyroid cells were extracted with ethanol/ethyl acetate and the various prostaglandins separated on silicic acid columns. Recoveries of added PGE(1)-(3)H and PGF(2alpha)-(3)H through the extraction and separation procedures ranged from 50-80%. The sensitivity of the method was 10-50 pg. Basal thyroid cell content of PGE(1) and PGF(2alpha) "equivalents" varied between cell preparations (range = 2-6 ng/0.2 ml cell suspension) but, in each instance, remained constant during 5-30-min incubations at 37 degrees C. TSH, 10-100 mU/ml, increased the levels of cell PGE(1) and PGF(2alpha) "equivalents" 30-80% above basal during 5-15-min incubations. The stimulatory effect was specific for TSH, no increase in PGE(1) or PGF(2alpha) "equivalent" levels being seen with luteinizing hormone (LH), human growth hormone (HGH), adrenocorticotropic hormone (ACTH), or glucagon. These data support the thesis that prostaglandins may mediate TSH effects on thyroid.
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PMID:Thyrotropin increases prostaglandin levels in isolated thyroid cells. 462 70


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