Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 36-year-old woman with nodular goiter, nervousness, and tachycardia was evaluated for T3 toxicosis. Her serum thyroxine level, resin T3 uptake, and thyroidal radioiodine uptake were normal. Her T3 (RIA), by a technique employing charcoal to separate bound and free T3, was reported as indeterminate due to an interfering substance; by a double-antibody method, her T3 (RIA) was 325 ng/dl. Further studies of the patient's serum revealed an abnormal T3-binding protein which misgrated in the beta-gamma globulin zone on paper electrophoresis and gel filtration chromatography (Sephadex G-200), and was precipitated from serum by rabbit anti-human Fab antibody. The gamma globulin fraction of the patient's serum, separated by a standard technique, showed strong binding activity toward [125I]T3, with an association constant of 4.1 X 10(8) 1/mole (Scatchard plot). In a similar system, labeled T4 was not bound. To avoid artefacts which this T3-binding protein might produce in assaying unextracted serum, T3 (RIA) was performed on an ethanol extract of serum and found to be 191 ng/dl, a slight elevation. However, the metabolic clearance rate of injected [125I]T3, estimated by non-compartmental analysis of the serum decay curve or by the specific activity or urinary T3, was about 16 1/day, a low value, so that the T3 production rate, 31 mug/day, was normal. The patient's symptoms disappeared with the resolution of domestic problems, and she appeared clinically euthyroid. Serum TSH was 5.0 uU/ml and antithyroglobulin titer, 1:16. A test for antibodies to thyroid microsomes was negative. We postulate that this subject was euthyroid, but had a concentration of T3-binding immunoglobulin which was sufficient to produce modest slowing of T3 turnover, borderline elevation of extractable T3 (RIA), and a major artefact in the T3 (RIA) measurement of unextracted serum. A similar abnormality may account for other instances of high T3:T4 ratios in serum.
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PMID:Triiodothyronine (T3)-binding immunoglobulins in a euthyroid woman: effects on measurement of T3 (RIA) and on T3 turnover. 126 40

Different processes implied in thyroid hormonogenesis (thyroglobulin, thyroperoxidase and hydrogen peroxide generating system expressions) and their regulation by TSH and iodide have been studied using porcine thyroid cells cultured in porous bottomed chambers. This system allowed to reproduce the functional bipolarity. Cells form a tight and polarized monolayer. Both apical and basolateral poles of epithelial cells were independently accessible and the cell layer separated two compartments which can contain different media. A major polarized secretion of thyroglobulin into the apical compartment was observed; it was increased in the presence of TSH as well as the thyroglobulin synthesis and mRNA level. These TSH effects were the consequence of adenylcyclase stimulation. Active transport of iodide, iodination of thyroglobulin and hormonosynthesis took place only in the presence of TSH. These steps occurred at the apical pole of cells. In the culture chamber system, thyroglobulin was weakly iodinated (6 atoms of iodide per mole of thyroglobulin; in vivo up to 40 atoms per mole) but hormonogenesis efficiency was close to this one observed in vivo (40%). Iodide concentrations higher than 0.5 microM daily added to the basal medium inhibited iodination of thyroglobulin and hormonosynthesis. Some components contained in culture media were inhibitors for iodination when they were present in the apical medium such as vitamins, amino acids and phenol red. The culture system appears to be interesting for pharmacological and toxicological studies.
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PMID:Hormonogenesis in thyroid cells cultured on porous bottom chambers. 144 62

The long-term iodination of thyroglobulin secreted into the apical medium of thyroid cells cultured as monolayers on porous bottom chambers reached 5.87 +/- 1.66 atoms of iodine/mol thyroglobulin after 11 days incubation in the presence of TSH (0.1 mU/ml) and iodide (0.5 microM) in the basal medium. This iodinated thyroglobulin contained thyroid hormones (T3 + T4) which involved 22.7% of the thyroglobulin iodine content. The iodoamino acid content was, in residues per mole, 2.2 +/- 0.35 for monoiodotyrosine, 0.74 +/- 0.04 for diiodotyrosine, 0.23 +/- 0.04 for T4, and 0.098 +/- 0.02 for T3. Kinetic studies showed that a minimal level of iodination (2.05 +/- 0.26 atoms iodine/mol thyroglobulin) was necessary for hormonogenesis. A maximal level of iodination and hormonogenesis was obtained with 0.5 microM iodide added daily to the basal medium. In these conditions, hormonogenesis efficiency reached about 40% (a value close to this one observed in vivo). Above 0.5 microM iodide, both iodination and T4 synthesis were inhibited (28.3% and 73.9%, respectively, for 1 microM iodide). Our culture system makes it possible to demonstrate that this high iodide concentration in the basal medium did not increase apical iodide concentration above 10 microM but decreased apical thyroglobulin concentration. The inhibitory effect of iodide on hormonogenesis cannot be due to a competition with tyrosine residues of thyroglobulin for their binding to thyroperoxidase although it could be related, at least in part, to a decrease in protein synthesis.
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PMID:Thyroid hormone synthesis in thyroglobulin secreted by porcine thyroid cells cultured on porous bottom chambers. Effect of iodide. 144 29

To determine the role of arginine vasopressin (AVP) in stress-induced release of anterior pituitary hormones, AVP antiserum or normal rabbit serum (NRS) was micro-injected into the 3rd ventricle of freely-moving, ovariectomized (OVX) female rats. A single 3 microliter injection was given, and 24 hours later, the injection was repeated 30 min prior to application of ether stress for 1 min. Although AVP antiserum had no effect on basal plasma ACTH concentrations, the elevation of plasma ACTH induced by ether stress was lowered significantly. Plasma LH tended to increase following ether stress but not significantly so; however, plasma LH following stress was significantly lower in the AVP antiserum-treated group than in the group pre-treated with NRS. Ether stress lowered plasma growth hormone (GH) levels and this lowering was slightly but significantly antagonized by AVP antiserum. Ether stress also elevated plasma prolactin (Prl) levels but these changes were not significantly modified by the antiserum. To evaluate any direct action of AVP on pituitary hormone secretion, the peptide was incubated with dispersed anterior pituitary cells for 2 hours. A dose-related release of ACTH occurred in doses ranging from 10 ng (10 p mole)-10 micrograms/tube, but there was no effect of AVP on release of LH. The release of other anterior pituitary hormones was also not affected except for a significant stimulation of TSH release at a high dose of AVP. The results indicate that AVP is involved in induction of ACTH and LH release during stress. The inhibitory action of the AVP antiserum on ACTH release may be mediated intrahypothalamically by blocking the stimulatory action of AVP on corticotropin-releasing factor (CRF) neurons and/or also in part by direct blockade of the stimulatory action of vasopressin on the pituitary. The effects of vasopressin on LH release are presumably brought about by blockade of a stimulatory action of AVP on the LHRH neuronal terminals.
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PMID:Role of arginine vasopressin in control of ACTH and LH release during stress. 298 9

Studies of several aspects of thyroid hormone economy have been conducted in 11 patients before and after removal of a molar pregnancy. Before evacuation of the mole, all patients demonstrated moderately to greatly elevated values for thyroidal (131)I uptake, absolute iodine uptake, and serum protein-bound-(131)I. Values for serum PBI and serum thyroxine (T(4)) concentration were consistently and often greatly increased, averaging more than twice those found in normal pregnancy and three times those in normal controls. On the other hand, the maximum binding capacity of the T(4)-binding globulin (TBG) was variably affected, and ranged between the values found in normal controls and those found in normal pregnancy. Values for the absolute concentration of free T(4) in serum were, on the average, only moderately elevated, since the proportion of free T(4) was moderately low, although not as low as in normal pregnancy. Sera of patients with molar pregnancy contained high levels of thyroid stimulating activity, as assessed in the McKenzie mouse bioassay system. The stimulator displayed a more prolonged duration of action than that of TSH and did not reveal a major immunological cross-reactivity with either human or bovine TSH, differing in the latter respect from the chorionic thyrotropin of normal human placenta. Abnormalities in iodine metabolism were rapidly ameliorated after removal of the molar pregnancy, and this was associated with the disappearance from serum of the thyroid stimulator. Despite the foregoing evidence of thyroid hyperfunction and hypersecretion of T(4), patients with molar pregnancy were neither goitrous nor overtly thyrotoxic. They did display, however, high values of the urinary pigment/creatinine ratio, a possible indication of the presence of a hypermetabolic state. It is concluded that in patients with molar pregnancy, thyroid function and T(4) secretion are stimulated, often greatly so, by an unusual thyroid stimulator which is demonstrable in the blood and which is probably of molar origin. The nature of the stimulator, as well as the reasons for both the variability of the increase in TBG which occurs in molar pregnancy and the lack of frank thyrotoxicosis, remain to be clarified.
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PMID:Alterations in thyroid hormone economy in patients with hydatidiform mole. 410 51

We describe a clinically euthyroid 60-year old woman with a past history of 1311 therapy for treatment of possible toxic nodular goitre. She had an elevated thyroxine level of 188 microgram/L (normal range 50-125 microgram/L) following her therapy, and her TSH was within normal limits at 4.7 mU/L. However her T3 level, as determined by an RIA technique employing charcoal to separate bound and free T3, was not measurable. T3 added to the patient's serum could not be recovered, therefore the presence of an unusual protein capable of binding T3 was suspected. To avoid this interference, T3 analysis was performed on an ethanol extract of the patient's serum and was found to be 17 microgram/L (normal range 0.8-1.8 microgram/L). At this time her thyroid microsomal antibody titre was 1:100,000. A protein, capable of binding more than 70% of the patient's T3, was demonstrated in the gamma globulin fraction by agarose gel electrophoresis. This protein did not bind T4. Scatchard analysis for T3 binding revealed a protein, presumably IGG, with a binding affinity of 2 x 109 L/mole and binding capacity of 50 microgram/L. This case exemplifies the caution that must be taken in interpreting thyroid function tests. When thyroid hormone levels are inappropriate to the clinical status of the patient the presence of circulating antibodies which can bind the thyroid hormones should be considered.
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PMID:Triiodothyronine--binding immunoglobulin in a euthyroid patient. 617 Apr 77

The production of TBG in liver increases during pregnancy. The thyroid stimulating substance is also suggested to exist in molar pregnancy. We have studied the thyroid functions with T4, T3, T3 resin uptake, TBG, free T4, TSH, HCG, TBG binding capacity and T4 binding by TBG in non-pregnant women, pregnant women and molar pregnant women. T4 and T3 levels were high during pregnancy and remarkably elevated in mole. TBG levels were 49.0 +/- 5.1/micrograms/ml in 3rd. trimester, which were 2.6 times higher than non-pregnant women and 38.4 +/- 8.4 micrograms/ml in mole. Res-O-Mat T3 values distributed within normal levels in 1st trimester and mole and higher in 3rd. trimester. Free T4 indices were almost normal during pregnancy and 2.4 times higher in mole. Free T4 levels, measured with dialysis and RIA, were slightly low during pregnancy but remarkably high in mole. Basal TSH levels were within normal range for these subjects. Beta-HCG levels in mole were greatly in excess of peak concentrations that were seen at 9-13 weeks of normal pregnancy. The significant correlations of beta-HCG with T4, T3 and free T4 index were found in mole, with coefficient of r = 0.691, 0.687, 0.644 respectively. The correlations of beta-HCG with free T4 and TBG were also suggested in mole. The levels of T4 binding by TBG were remarkably elevated for incremental TBG in mole, which pattern was particular for thyroid hyperfunction. From the above results, we considered that euthyroidism is sustained during pregnancy and thyroid stimulating substance existed in mole. That substance is probably HCG, which is remarkable elevated in mole.
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PMID:[T4, T3, T3 resin uptake, TBG and free T4 levels for thyroid functions in normal and molar pregnancy (author's transl)]. 680 12

A case is reported of a Senegalese patient admitted for hydatiform mole. The serum human chorionic gonadotrophin concentration (hCG) was 900,000 UI.l-1. The patient was recognized to be clinically hyperthyroid with raised T4 and T3 values, but a very low TSH concentration. After two days of beta adrenergic blockade and carbimazole, a suction curettage was performed under general anaesthesia. Propranolol was again administered 6 hours after the surgery. Thyroid function returned to normal level two weeks after removal of the mole, suggesting that hCG was responsible for the thyrotoxicosis. Serum hCG concentrations closely paralleled those of free thyroxine, but the correlation was difficult to assess because of carbimazole. Clinical thyrotoxicosis is rare in molar pregnancy. The diagnosis being made in semi-urgent conditions, this raises the question of how to obtain rapid stabilization of the disease before surgery.
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PMID:[Hyperthyroidism induced by molar pregnancy]. 827 31

There is abundant evidence that human chorionic gonadotropin (hCG) is a weak thyrotropin (TSH) agonist. In FRTL-5 rat thyroid cells, hCG increases cyclic adenosine monophosphate (cAMP), iodide transport, and cell growth. hCG has thyroid-stimulating activity in bioassays in mice and in clinical studies in man. In cultured cells transfected with the human TSH receptor, hCG increases generation of cAMP. Molecular variants of hCG with increased thyrotropic potency include basic molecules with reduced sialic acid content, truncated molecules lacking the C-terminal tail, or molecules in which the 47-48 peptide bond in the beta-subunit loop is nicked. In normal pregnancy, when hCG levels are highest at 10 to 12 weeks gestation, there is suppression of serum TSH levels, presumably due to slight increases in free thyroxine (T4) concentration. In twin pregnancies, hCG levels tend to be higher and suppressed TSH levels are more frequent. Hyperemesis gravidarum, defined as severe vomiting in early pregnancy that causes 5% weight loss and ketonuria, is usually associated with increased hCG concentration. A high proportion of patients with hyperemesis gravidarum, about one-third to two-thirds in different series, have evidence of increased thyroid function. Only a small proportion of these patients have clinical hyperthyroidism, termed gestational thyrotoxicosis. These patients probably secrete a variant of hCG with increased thyroid-stimulating activity. Trophoblastic tumors, hydatidiform mole, and choriocarcinoma often cause hyperthyroidism because they secrete very large amounts of hCG. When the serum hCG exceeds about 200 IU/mL, hyperthyroidism is likely to be found. There is a correlation between the biochemical severity of hyperthyroidism and the serum hCG in these patients. Removal of the mole or effective chemotherapy of the choriocarcinoma cures the hyperthyroidism. In conclusion, hCG has thyroid-stimulating activity that influences thyroid function early in pregnancy when hCG levels are high. Excessive hCG secretion may cause hyperthyroidism in patients with hyperemesis gravidarum or trophoblastic tumors.
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PMID:Human chorionic gonadotropin and the thyroid: hyperemesis gravidarum and trophoblastic tumors. 1044 9

We evaluated the stimulation of Chinese hamster ovary cells expressing human thyrotropin receptors (CHO-hTSHR cell) by sera of five patients with hydatidiform mole before and after the evacuation of the mole, and compared the results with serum human chorionic gonadotropin (hCG) concentrations and serum free thyroid hormones in these patients. Significantly increased CHO-hTSHR cell stimulating activities were observed in sera from untreated patients, and the activity decreased promptly after the evacuation of the mole, concomitantly with the decrease in serum hCG and free thyroid hormones. CHO-hTSHR cell stimulating activity of sera of the untreated patients significantly correlated with serum hCG. Moreover, serum hCG stimulated CHO-hTSHR cells in a dose dependent manner similar to the dose-response curve of the stimulation by purified hCG. Sera of the patients and purified hCG did not stimulate nontransfected CHO-K1 cells. However, a significant correlation was not observed between serum-free thyroid hormones and serum hCG or between serum free thyroid hormones and CHO-hTSHR cell stimulating activities in untreated patients. These results indicate that serum hCG from patients with hydatidiform mole stimulates thyroid gland by interacting with TSH receptors, and suggest that the increase in thyroid hormones in patients may depend on both the increased serum hCG and the responsiveness of their thyroid glands to hCG.
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PMID:Stimulation of Chinese hamster ovary cells expressing human thyrotropin receptors by serum human chorionic gonadotropin of patients with hydatidiform mole. 1064 59


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