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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In human thyrocytes and in a permanent CHO cell line expressing the human thyroid stimulating hormone (TSH) receptor cDNA (JP09 cells), TSH activates both the cyclic AMP and the phosphatidylinositol 4,5-bisphosphate (PIP2) cascade, although the latter effect requires higher TSH concentrations. Thyroid stimulating autoantibodies (TSAb) activate also the human thyroid leading to the hyperthyroidism of Graves' disease. They bind to the TSH receptor and mimic the TSH stimulation of the gland by increasing intracellular cyclic AMP, but they do not enhance PIP2 hydrolysis in human thyroid slices. We show in this study that TSAb are able to activate the PIP2 cascade in JP09 cells, a cell line expressing high levels of TSH receptor. This suggests that the mechanism of action of TSAb on the TSH receptor is qualitatively similar to that of TSH.
Mol Cell Endocrinol 1992 Oct
PMID:Thyroid stimulating immunoglobulins, like thyrotropin activate both the cyclic AMP and the PIP2 cascades in CHO cells expressing the TSH receptor. 136 Sep 26

Previous studies have demonstrated that in different cardiac preparations action potential duration (APD) increases with age. As in various species, thyroid hormone levels increase developmentally, and since hyperthyroidism shortens APD while hypothyroidism prolongs it, we hypothesized that developmental changes in APD result from age-related variations in the thyroid state. The hypothesis was tested by analysing ventricular action potentials and total T4 (TT4) levels in guinea-pigs in the age range of 0 days to 3 months (adult), and in hyperthyroid and hypothyroid newborns (0-5 days old). We found that APD50 increased exponentially with age with a time constant of 6.7 days, from 100.6 +/- 3.4 ms in newborns (0-5 days old) to 147.4 +/- 5.2 ms in adults (P less than 0.001). TT4 decreased exponentially with age with a time constant of 4.8 days, from 3.9 +/- 0.4 micrograms/dl in newborns to less than 1.0 microgram/dl in adults. In the age range studied, APD50 and TT4 were linearly correlated: Y = -12.13X + 142, r - 0.865. In contrast to the marked changes in APD, resting potential and action potential amplitude were age-independent, and Vmax only slightly increased with age. Alterations in the thyroid state in newborns affected ventricular action potentials as predicted by the hypothesis. In euthyroid (TT4 = 3.9 +/- 0.4 micrograms/dl), hypothyroid (TT4 = 1.6 +/- 0.4 micrograms/dl) and hyperthyroid (TT4 = 39.8 +/- 10.8 micrograms/dl) newborns, APD50 was: 100.6 +/- 3.4 ms, 117.7 +/- 4.2 ms and 63.7 +/- 7.4 ms, respectively (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1991 Jul
PMID:Developmental changes in ventricular action potential properties in guinea-pigs are modulated by age-related changes in the thyroid state. 179 30

Plasma androstanediol-glucuronide (ADG) is considered by many authors to be a highly reliable parameter of peripheral androgenicity. Recently, several authors have questioned the reliability of the ADG levels as a parameter of androgenicity. Our data obtained by continuous infusion experiments showed that in women the adrenal steroids, dehydroepiandrosterone sulfate, androstenedione and dehydroepiandrosterone are the major precursors of plasma ADG, accounting for almost the totality of circulating ADG. As expected, in view of its precursors, ADG levels decrease significantly with age. Dexamethasone causes a significant decrease of these levels, whereas in women with Addison's disease the levels are only 20% of normal levels; ovariectomy hardly influences ADG levels. Our data show that in women with moderate hirsutism, plasma ADG levels are no more often increased than the other androgens. In virilizing syndromes ADG levels are higher than expected from precursor levels, suggesting an increased 5 alpha-reductase activity. In hyperthyroidism as well as in euthyroid women with isolated suppressed thyroid stimulating hormone, ADG levels are increased without any sign of virilism. In men, ADG levels have testosterone as a major precursor, but the adrenals contribute to +/- 30% of ADG levels. After transdermal dihydrotestosterone gel, free androstanediol levels increased by a factor of 40, but ADG levels were only increased by a factor of 4, suggesting that the skin is not very effective in conjugating androstanediol. It is concluded that ADG levels in women reflect essentially adrenal precursor levels as well as 5 alpha-reductase activity in peripheral tissues inclusive of the liver.
J Steroid Biochem Mol Biol 1991 Nov
PMID:Physiopathology of plasma androstanediol-glucuronide. 183 5

A phase II clinical trial was conducted using subcutaneous recombinant human interleukin-2 (rIL-2, EuroCetus) and subcutaneous interferon-alpha 2b (rIFN-alpha 2b, Essex) in patients with advanced cancer. Safety and tolerance of this outpatient regimen were assessed in 17 patients with progressive metastatic renal carcinoma, 14 of whom were evaluable for clinical response to combined rIL-2 and rIFN-alpha 2b. In this study, rIL-2 was administered every 12 hours, at 1.5 million (Cetus) U/m2 on days 1 and 2, followed by 0.3 million U/m2 5 days per week for 6 consecutive weeks. Concomitantly, rIFN-alpha 2b was given as 5 million U/m2 three times weekly for 6 consecutive weeks. Patients presenting with stable or regressive disease after 6 weeks of rIL-2 and rIFN-alpha 2b (11 of 14) were scheduled to repeat combination therapy. After one treatment cycle, five of 14 patients presented with partial remission; two of these patients achieved complete regression of metastatic lesions. After therapy, six patients have been in stable disease for up to 8 months. toxicity of this regimen was moderate, with local inflammation of the injection sites, grade I-II (World Health Organization criteria) fevers, chills, malaise, nausea and/or vomiting, and anorexia in 70% to 100% of patients treated. After 6 weeks of rIL-2 and rIFN-alpha 2b, laboratory evidence of treatment-related hypothyroidism and hyperthyroidism was obtained in one and four patients, respectively. Immunogenicity of sc rIL-2 was mostly limited to the development of nonneutralizing antibodies that occurred in approximately 40% of patients. None of the patients exhibited antibodies specific to rIFN-alpha 2b.
Mol Biother 1990 Sep
PMID:Subcutaneous interleukin-2 and interferon-alpha 2b in patients with metastatic renal cell cancer: the German outpatient experience. 222 98

Recombinant interleukin-2 (rIL-2; EuroCetus, Amsterdam, Netherlands) was studied in an outpatient phase II trial in 14 patients with progressive metastatic renal carcinoma, malignant melanoma, and colorectal cancer. Escalating doses of rIL-2 were administered as subcutaneous bolus every 12 hours, starting at 0.3 million U/m2/d. A 100% dose increase occurred at weekly intervals, up to a maximum of 2.4 million U/m2/d. Responding patients or patients with stable disease after 4 weeks of rIL-2 (n = 9) were continued on maintenance therapy at 1.8 million U/m2 of rIL-2 administered once weekly. After 12 weeks of therapy, one renal cell cancer patient had a partial regression in lung metastases. Bolus injection of rIL-2 (1.2 million U/m2) resulted in peak serum levels of 25 to 30 U/ml. Toxicity of this regimen was moderate, with local inflammation at the injection sites, grade I-II (World Health Organization) malaise, nausea and/or vomiting, and fevers in 70% to 100% of patients treated. Thyroid dysfunction was observed in 10 patients receiving subcutaneous rIL-2; four of these patients had laboratory evidence of hyperthyroidism, and one had hypothyroidism. rIL-2-induced toxicity reversed spontaneously after cessation of treatment. In all patients receiving rIL-2, a dose-dependent increase in peripheral blood lymphocyte and eosinophil counts was noted, with a mean of 2.6 and 3.8 x 1,000/microliters after 4 weeks of therapy; mean lymphocyte and eosinophil counts were measured at 2.0 and 2.4 x 1,000/microliters in patients who received prior high-dose chemotherapy, compared with 3.2 and 5.1 x 1,000/microliters in those who did not.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Biother 1990 Mar
PMID:Low-dose subcutaneous recombinant interleukin-2 in advanced human malignancy: a phase II outpatient study. 233 34

Chronic alterations in the thyroid state have been shown to induce marked changes in action potential characteristics, the most pronounced being shortening of action potential duration (APD) by hyperthyroidism and an increase in duration by hypothyroidism. In the present study our major objectives were to investigate the time course of the effect of thyroid hormone on action potential characteristics, to examine the relationships between thyroid hormone levels and these changes, and to test whether the electrophysiological alterations are induced both by thyroxine (T4) and triiodothyronine (T3). The major findings were that a single dose of either hormone (100 micrograms/kg) caused a marked shortening of APD, while resting potential, action potential amplitude and Vmax were unchanged. APD shortening was observed promptly after ip T4 or T3 administration, with maximal effect occurring within 2 to 3 hrs. Having determined thyroid hormone levels in the guinea-pigs used for the electrophysiological experiments, we found a close temporal association and inverse linear relationships (r = -0.82) between total T4 levels and APD. To determine whether APD shortening is induced due to a direct effect of thyroid hormone on the myocardium, euthyroid papillary muscles were superfused with 10(-6) M T3; within 3 hrs of superfusion with T3, APD was shortened from 148.8 +/- 4.7 ms to 117.7 +/- 6.4 ms (P less than 0.01), an effect blocked by the protein synthesis inhibitor cycloheximide. Our results demonstrate that thyroid hormones affect the duration of the ventricular action potential in a concentration dependent fashion. Furthermore, the study suggests that thyroid hormones affect the myocardium directly via mechanism(s) that are probably associated with thyroid hormone-related protein synthesis.
J Mol Cell Cardiol 1989 Nov
PMID:Electrophysiological effects of thyroid hormones in guinea-pig ventricular muscle: time course and relationships to blood levels. 260 46

Since we have previously reported that hyperthyroidism induces adipose tissue hyperplasia in the young rat, the effect of thyroid hormones on growth and differentiation of preadipocytes from retroperitoneal (RPAT) and epididymal (EAT) adipose tissue was studied in a primary culture system which allows a precocious cell differentiation. In this culture system, preadipocytes from RPAT exhibited a greater potentially to differentiate than cells from EAT. Chronic exposure to triiodothyronine (T3) induced an acceleration of the differentiating process as shown by a transient increase of the number of differentiated cells without alteration of cell multiplication. This effect was more important in cultures of cells from RPAT than from EAT. T3 was ineffective on lipoprotein-lipase activity but induced a stimulation of the esterification pathway which was durable and could likely be related to an increased lipid turn-over. T3 induced also a stimulation of fatty acid biosynthesis, only on the first stages of morphological differentiation which suggests that this effect could be specifically in relation with the stimulation of adipose conversion.
Cell Mol Biol 1989
PMID:Acceleration by triiodothyronine of adipose conversion of rat preadipocytes from two adipose localizations. 270 55

Mammalian species differ in their myocardial responsiveness to cardiac glycosides; whereas glycosides induce a marked positive inotropic effect in species such as dog, rabbit and guinea-pig, the rat myocardium is virtually insensitive. We investigated the physiological basis for this phenomenon by testing the hypothesis that the inter-species variations in the response of the myocardium to cardiac glycosides results, at least in part, from species-related differences in the "thyroid status". In the present study we focused on the toxic effects of the glycosides, and studied ouabain-induced delayed afterdepolarizations (DAD): (1) in guinea-pigs, rats and mice, which encompass a wide range of thyroid statuses, as indicated by their O2 consumption and thyroid hormone levels; (2) in guinea-pigs and rats in which the thyroid status was decreased by propylthiouracil treatment or increased by thyroxine administration (in the former species only). DAD were readily induced in guinea-pigs after 40 to 60 min superfusion with 10(-6) M ouabain and 5.4 mM Ca2+. In rats, DAD were induced only when the Ca2+ concentration was raised to 8.1 mM, but were absent in mice even after 2 h of superfusion with ouabain and 8.1 mM Ca2+. In guinea-pigs and rats (at cycle length = 500 ms), DAD amplitude was (means +/- S.E.): 2.8 +/- 0.7 mV and 1.1 +/- 0.4 mV, respectively. The slope of the DAD ascending limb (dV/dt) in guinea-pigs was 47.6 +/- 8.6 mV/s and in rats was 8.1 +/- 3.4 mV/s. In both species DAD characteristics were altered by the thyroid status. In eu-, hyper- and hypothyroid guinea-pigs, DAD amplitude and dV/dt (cycle length = 500 ms) were as follows: 2.8 +/- 0.7 mV and 47.6 +/- 8.6 mV/s; 1.2 +/- 0.4* mV and 12.6 +/- 3.9* mV/s; 7.5 +/- 0.6* mV and 204.0 +/- 18.4* mV/s, respectively (*, P less than 0.005, compared to euthyroid guinea-pigs). The occurrence of triggered beats was also dependent on the thyroid status. They occur more frequently in hypothyroidism and less frequently in hyperthyroidism. Hypothyroidism in rats augmented ouabain toxicity as reflected by an increase in DAD amplitude and dV/dt by 109% and 105%, respectively (P less than 0.05, as compared to euthyroid rats). In conclusion, we suggest that species-related differences in the thyroid status may contribute to the inter-species (as well as for the intra-species) variations in the myocardial responsiveness to cardiac glycosides.
J Mol Cell Cardiol 1989 Feb
PMID:Inter-species variations in myocardial responsiveness to cardiac glycosides: possible relations to the thyroid status. 274 48

Increasing evidence is accruing in favour of the view that autoimmune thyroid disease is due to an organ-specific defect in suppressor T lymphocytes that is genetically induced. While the initial evidence supporting this hypothesis was based on results with the migration inhibition factor test, subsequent investigations from our own and other laboratories have confirmed the presence of such an organ-specific suppressor T lymphocyte defect in autoimmune thyroid disease. Moreover, there is now good evidence that hyperthyroidism per se has an effect on suppressor T lymphocyte function and numbers, and this is superimposed on and is additive to the organ-specific defect while patients are hyperthyroid; this may well act as a self-perpetuating factor in continuing the disease. It has been proposed elsewhere that the expression of HLA-DR antigen on the cell membrane of the thyrocytes (possibly induced by viral infection) represents the initial inductive step in precipitating autoimmune thyroid disease in persons predisposed by virtue of having an immunoregulatory defect in the first place. However, there is now evidence that: (1) normal thyrocytes respond equally well to various stimuli in terms of DR expression when compared to Graves' or Hashimoto's thyrocytes; (2) supernatants from normal T lymphocytes will stimulate DR expression on thyrocytes at least as well as supernatants from Graves' T lymphocytes when stimulated by non-specific lectins; (3) conversely, Graves' T lymphocytes will stimulate thyroid DR expression more markedly than normal T lymphocytes when the lymphocyte-thyrocyte interaction is direct; (4) monocytes and helper T lymphocytes are essential for thyrocyte DR expression; (5) DR expression on thyrocytes does not lead to a self-perpetuating immune response. From all of these observations, it seems evident that DR expression is secondary to the primary immune assault in autoimmune thyroid disease, and is neither an initiating event, nor unique to autoimmune thyroid disease, nor a self-perpetuating phenomenon.
Mol Biol Med 1986 Feb
PMID:Autoimmune thyroid disease--a perspective. 287 Apr 10

The effect of thyroid status on the postnatal development of the two molecular forms of Na+,K+-ATPase, distinguished kinetically on the basis of their ouabain sensitivity, was examined in rat brain. Hypothyroidism induced by PTU from day 1 postnatally significantly reduced the Na+,K+-ATPase activity in cerebellum (22-30 days) but not forebrain, whereas hyperthyroidism (T4 treatment from day 1) had no effect. The hypothyroidism-induced reduction in cerebellum was reflected by a 20-45% reduction in the activity of the alpha(+) form of Na+,K+-ATPase (high ouabain affinity) against control brains compared to a 60-70% reduction in the activity of the alpha form (low ouabain affinity). These results show that neonatally induced hypothyroidism leads to a selectively greater impairment of the ontogenesis of the activity of cerebellar alpha form of Na+,K+-ATPase. This may possibly reflect a retarded development of a selective cerebellar cell population containing predominantly the alpha form of the enzyme.
Mol Cell Endocrinol 1985 May
PMID:Effect of thyroid status on the development of the different molecular forms of Na+,K+-ATPase in rat brain. 298 30


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