Long-acting Thyroid Stimulator Research Articles

Transcatheter arterial chemoembolization combined with Hippo/YAP inhibition significantly improve the survival of rats with transplanted hepatocellular carcinoma

BackgroundThis study aimed to explore the effect of inhibiting the Hippo/Yes-associated protein (YAP) signaling pathway on the outcomes of transcatheter arterial chemoembolization (TACE) in treating transplanted hepatocellular carcinoma (HCC).MethodsA transplanted HCC rat model was established. Then, rats were randomly divided into four groups: Sham, TACE, verteporfin (inhibitor of Hippo/YAP), and TACE+verteporfin. Lent-OE-YAP was transfected into rats to overexpress YAP in vivo. After treatments, morphological changes, tumor weight, and the overall survival of rats in different groups were analyzed. Real-time PCR, immunohistochemistry staining, and Western blotting were used to determine the expression of factors related to the Hippo/YAP signaling pathway.ResultsTumor weight and tissue lesions in the TACE and verteporfin groups were significantly reduced compared with the Sham group. Verteporfin significantly decreased tumor weight after TACE treatment. In addition, verteporfin significantly improved the overall survival of rats with transplanted HCC after TACE treatment. Compared with the Sham group, both TACE and verteporfin groups exhibited significantly decreased expression of macrophage-stimulating (MST)1, MST2, long-acting thyroid stimulator 1, transcriptional co-activator with PDZ-binding motif (TAZ), Yes-associated protein (YAP), TEA domain transcription factor (TEAD)1, TEAD2, TEAD3, and TEAD4. TACE plus verteporfin significantly enhanced the downregulation of effectors in the Hippo/YAP signaling pathway and decreased tumor size, while the overexpression of YAP exerted opposite effects.ConclusionThe inhibition of the Hippo/YAP signaling pathway via verteporfin significantly improved the outcomes of TACE in treating transplanted HCC.

Bioassays for TSH Receptor Autoantibodies, from FRTL-5 Cells to TSH Receptor-LH/CG Receptor Chimeras: The Contribution of Leonard D. Kohn.

Since the discovery 60 years ago of the “long-acting thyroid stimulator” by Adams and Purves, great progress has been made in the detection of thyroid-stimulating hormone (TSH) receptor (TSHR) autoantibodies (TRAbs) in Graves’ disease. Today, commercial assays are available that can detect TRAbs with high accuracy and provide diagnostic and prognostic evaluation of patients with Graves’ disease. The present review focuses on the development of TRAbs bioassays, and particularly on the role that Leonard D. Kohn had in this. Indeed, 30 years ago, the Kohn group developed a bioassay based on the use of FRTL-5 cells that was characterized by high reproducibility, feasibility, and diagnostic accuracy. Using this FRTL-5 bioassay, Kohn and his colleagues were the first to develop monoclonal antibodies (moAbs) against the TSHR. Furthermore, they demonstrated the multifaceted functional nature of TRAbs in patients with Graves’ disease, with the identification of stimulating and blocking TRAbs, and even antibodies that activated pathways other than cAMP. After the cloning of the TSHR, the Kohn laboratory constructed human TSHR–rat luteinizing hormone/chorionic gonadotropin receptor chimeras. This paved the way to a new bioassay based on the use of non-thyroid cells transfected with the Mc4 chimera. The new Mc4 bioassay is characterized by high diagnostic and prognostic accuracy, greater than for other assays. The availability of a commercial kit based on the Mc4 chimera is spreading the use of this assay worldwide, indicating its benefits for these patients with Graves’ disease. This review also describes the main contributions made by other researchers in TSHR molecular biology and TRAbs assay, especially with the development of highly potent moAbs. A comparison of the diagnostic accuracies of the main TRAbs assays, as both immunoassays and bioassays, is also provided.

Hyperthyroidism, Exophthalmos, and Goiter: Historical Notes on the Orbitopathy

Exophthalmos associated with goiter and/or symptoms of hyperthyroidism have been known since antiquity. It was not until around 1800 that a number of studies described this disorder in more detail. For many years the nature of the disease remained unclear and it was appreciated as either a cardiac or neurological disease. There was no agreement on treatment. Surgery on the thyroid, orbit, autonomous nerve system, and pituitary has been employed. Medical treatment was introduced around World War II. Later, as a consequence of the discovery of long-acting thyroid stimulator, it became apparent that Graves-Basedow's disease was an autoimmune disease and so was the exophthalmos, though many details of the pathophysiology remain in doubt. This article presents a brief review of the history of the exophthalmos associated with thyroid disease.

A functional site on the human TSH receptor: a potential therapeutic target in Graves' disease.

Identifying sites on the TSH-receptor that are involved in the pathological stimulation of the thyroid by autoantibodies in Graves' disease would aid the development of new therapies. We tested a series of monoclonal antibodies that recognize the native receptor for their ability to inhibit stimulation of the receptor in vitro. Heterologous cells expressing the recombinant human TSH-receptor were stimulated with TSH or serum samples from 13 Graves' disease patients or the MRC Long-Acting Thyroid Stimulator standard B (LATS-B) and their cAMP responses measured. The effect on this stimulation of various doses of purified monoclonal antibodies with defined epitopes was determined. Antibodies against one epitope (residues 381-384) inhibited TSH-stimulated cyclic adenosine monophosphate (cAMP) production (1 microg/ml causing 50% inhibition of the response to 100 microU/ml TSH) and also inhibited cAMP production induced by sera from approximately 40% (6/14) of Graves' disease patients, including the MRC LATS-B standard. Residues 381-384 of the human TSH-receptor are important in the physiological and pathological stimulation of the thyroid. This opens the possibility of more specific therapy of some Graves' disease patients by agents directed against this epitope.

Receptor autoimmunity in endocrine disorders

The discovery in 1956 of the long-acting thyroid stimulator of Graves' disease, now known as thyroid-stimulating antibodies, was seminal. A new mechanism for disease was revealed that appears applicable to virtually all endocrine systems, involving the growth as well as the function of endocrine cells. An endocrine gland may fail through at least three autoimmune mechanisms: destruction, atrophy, and inhibition of function. Destruction is probably irreversible but is not usually distinguishable clinically from receptor blockade causing atrophy or from metabolic unresponsiveness. The contribution made by receptor autoimmunity to endocrine diseases other than thyroid disease is at present unclear, but with immunologic manipulation it is potentially reversible, improving the replicative capacity of the gland, its metabolic responsiveness, or both.

Receptor Autoimmunity in Endocrine Disorders

The discovery in 1956 of the long-acting thyroid stimulator of Graves' disease, now known as thyroid-stimulating antibodies, was seminal. A new mechanism for disease was revealed that appears applicable to virtually all endocrine systems, involving the growth as well as the function of endocrine cells. An endocrine gland may fail through at least three autoimmune mechanisms: destruction, atrophy, and inhibition of function. Destruction is probably irreversible but is not usually distinguishable clinically from receptor blockade causing atrophy or from metabolic unresponsiveness. The contribution made by receptor autoimmunity to endocrine diseases other than thyroid disease is at present unclear, but with immunologic manipulation it is potentially reversible, improving the replicative capacity of the gland, its metabolic responsiveness, or both.

Clinical significance of anti-TSH antibody in sera from patients with Graves’ disease and other thyroid disorders

In a survey of patients having anti-TSH antibody (TSH Ab), data from 167 subjects were collected from 8 Japanese Institutions. They were divided into a high TSH Ab group consisting of 63 cases; since the means of assay was via a subnormal thyrotropin binding inhibitor immunoglobulin (TBII) assay, this group had TBII values less than -20%. An additional low TSH Ab group was made up of 104 cases. Out of a total of 11,211 patients, the incidence of TSH Ab for the high and low groups were 0.57% and 13.4%, respectively. More than 95% of these TSH Ab carriers had Graves' disease or some other autoimmune thyroid disorder, and anti-thyroglobulin and anti-thyroid microsomal antibodies were detected similarly in both groups. It was significant that TSH receptor antibodies could also be detected in both groups, namely, thyroid stimulating antibody and long acting thyroid stimulator (LATS) in 4 of 9 patients in the high TSH Ab group and TBII in 55 of 104 in the low TSH Ab group, respectively. The high TSH Ab levels tended to persist, but 26% of cases showed disappearance or appearance of the antibody during the observation period. In one Graves' patient, a moderate TBII activity (64.2%) was followed by markedly elevated TSH Ab (TBII: -83.4%) within 2 months. The TSH Ab in the low TSH Ab group disappeared in most cases. Also, fluctuations in TSH Ab did not always parallel those seen for TBII and reciprocal fluctuation pattern (transient or otherwise) were observed in 33%. In conclusion, anti-TSH antibody is produced frequently in patients with either Graves' disease or some other autoimmune thyroid disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperthyroidism associated with adenomatous goiter in an infant

We operated on a 5-year-old girl with adenomatous goiter and hyperthyroidism. Since the age of 6 months, the patient had had delayed growth and a large goiter; the serum level of thyroid iodine was high, and the diagnosis of hyperthyroidism was made. Treatment with propylthiouracil (PTU) was started. Circulating thyrotropin receptor antibody and long-acting thyroid stimulator were not detected. The patient continued to require PTU to remain euthyroid. When she was 5, the goiter was enlarged, and subtotal thyroidectomy was done. The diagnosis of adenomatous goiter was made. The postoperative course was uneventful. Two years after the operation, the patient remains euthyroid without medication.

Universal Predictive Criteria for Neonatal Overt Thyrotoxicosis Requiring Treatment

The universal predictive criteria for neonatal overt thyrotoxicosis requiring treatment were examined in 108 neonates (including a pair of twins) born to mothers with Graves' disease (36 patients under treatment with antithyroid drugs [group A] and 71 in remission [group B]). Anti-thyroid-stimulating hormone (TSH) receptor antibody activity was measured by both radioreceptor assay (TSH-binding inhibitor immunoglobulin [TBII]) and biologic stimulation assay (thyroid stimulating antibody [TSAb]). For generalization of the predictive criteria, the expression of TBII activity was standardized using standard serum made taking units of Medical Research Council long-acting thyroid stimulator, standard B as a reference, and expression of TSAb activity was standardized using bovine TSH as a standard. TBII activity was positive in 22 mothers at delivery, and TSAb activity was positive in 18. In 12 cases, both activities were positive. Both the TBII and the TSAb activity of maternal serum at delivery correlated well with that of the cord serum. Neonatal thyrotoxicosis occurred in 9 of 108 neonates (8%), of whom five (5%) had clinical overt symptoms requiring antithyroid drug treatment. In all nine cases the TBII and TSAb activities were both positive, but no neonate without TBII or TSAb activity developed thyrotoxicosis. The prediction rate (42%) of neonatal overt thyrotoxicosis was higher when both TBII and TSAb were measured than when only TBII (23%) or TSAb (28%) was measured. Clinical overt thyrotoxicosis could be predicted in five of six neonates (83%) of mothers when the cutoff levels of antibody activities were increased to a TBII activity of above 8 U/ml and TSAb activity of above 1.0 TSH microUEq.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-acting thyroid stimulator: how receptor autoimmunity was discovered.

Long-acting thyroid stimulator: how receptor autoimmunity was discovered.

The pathogenesis and treatment of Graves' ophthalmopathy.

Graves' ophthalmopathy (GO) is probably an autoimmune condition although the pathogenesis is still not fully understood. GO is frequently, though not invariably, associated with Graves' disease and it may in fact be a separate disease entity. Ophthalmopathy is commonest in the 30 to 50 age group,2'3 and is more common in women (2:1, female:male), although the female preponderance is not so marked as in Graves' disease where the ratio is 6:1.4,5,6 A family history of autoimmune thyroid disease is frequently present which may or may not be accompanied by ophthalmopathy. The pattern of inheritance is not a simple one and no single gene appears to be implicated. In Graves' disease it is likely that the genes conferring susceptibility are associated with the major histocompatibility genes and expression of major histocompatibility antigens B8 and DR3 confers an increased risk for Graves' disease.4'7 The most striking pathological feature ofGO is the marked increase in muscle bulk. The eye muscles show lymphocytic infiltration and have increased intercellular spaces with mucopolysaccharide and water. The structure ofthe muscle is usually normal although there may be swelling ofthe fibres and loss ofstriations and in more severe cases fibre atrophy and disordered muscle structure. The retrobulbar connective tissue also contains numerous lymphocytes and fibroblasts and there is proliferation of the connective tissue with newly formed collagen. The spaces between the collagen fibres contain amorphous material, mainly hyaluronic acid and other glycosaminoglycans which increase the osmotic pressure and trap water. The main result of all these changes is an increase in the total orbital contents. The presence ofimmune response cells in the orbit, the deposition of immunoglobulins on orbital tissues and the association with autoimmune thyroid disease suggests that the underlying mechanism is an autoimmune process. Cell-mediated immune responses and antibodies against eye muscle antigens have been identified but it is not known whether the damage results from cell-mediated immunity, circulating immune complexes or pathogenic antibodies. Cellmediated immunity has been clearly demonstrated with the production of macrophage migration inhibition factor (MIF) by sensitized T lymphocytes in response to retro-orbital antigens using both crude orbital antigens consisting of muscle and fat' and retro-orbital muscle.9 Attempts to purify the antigen from retro-orbital tissue suggested that thyroglobulin or a derivative was responsible,'0 although there has been no confirmatory evidence for this. T cell subsets have not been studied extensively inGO but two cases with abnormal helper:suppressor T cell ratios and increased circulating activated T cells have been described. Lymphocytes from patients with GO have been shown to induce lysis in eye muscle cells'2 and lymphocytes incubated with fibroblasts provoke an increase in glycosaminoglycans.'3 Antibodies, termed ophthalmic immunoglobulins, have been described in the serum of patients with GO which bind specifically to eye muscle membranes.'4 The specific nature of ophthalmic immunoglobulins was shown by failure to neutralize binding to eye muscle by pre-incubation of serum with membrane preparations from other tissues. Pre-incubation of thyrotrophin-binding-inhibiting immunoglobulin (TBII) with eye muscle membranes did not result in loss of thyroid stimulating hormone (TSH) binding inhibition. There was no correlation ofophthalmic immunoglobulins with microsomal antibody, thyroglobulin antibody, or TBII in serum of patients with Graves' disease.' While thyroid-stimulating antibody (TSAb) is responsible for the hyperthyroidism of Graves' disease it does not appear to cause the ophthalmopathy. There is a dissociation clinically between GO and hyperthyroidism,15 a lack of correlation between long-acting thyroid stimulator (LATS), TBII, or TSAb activity and eye disease, a poor correlation between TBII and ophthalmic immunoglobulins, and pre-incubation of LATS or TBII with eye muscle membranes or other

Stimulation of thyroidal iodothyronine 5'-monodeiodinase by long-acting thyroid stimulator (LATS).

To evaluate the effect of long-acting thyroid stimulator (LATS) on thyroid iodothyronine monodeiodinating activity, we have studied the in vitro conversion of T4 to T3 by mouse thyroid homogenate comparing tissue from LATS treated (0.1 ml LATS(+) serum, ip, for 3 days) with tissues from LATS(-) Graves' disease patients' serum or normal serum treated controls. Five out of seven LATS(+) sera were shown to stimulate the T4 5'-deiodinase significantly in mouse thyroid. There was no significant correlation between LATS titre and deiodinase activities in the different sera tested. To compare the effect of LATS and TSH (0.2 IU, ip daily), studies were carried out from 12 to 72 h. LATS had a similar latency of 12 h on the stimulation of thyroid deiodinase compared to TSH as reported earlier. However, the conversion activities reached a plateau by 12 h after LATS treatment, while it continued to rise upon daily TSH injection from 24 to 72 h. In addition, TSH caused a marked reduction of thyroid protein and an early peaking in serum T3 and T4 at 12 h, whereas LATS caused no detectable change in thyroid protein and a gradual rise in circulating T3 and T4. The kinetic analysis indicated that LATS-mediated stimulation of T4 5'-deiodinase was, similar to TSH, associated with an increase in maximum velocity (Vmax were 139, 208 and 505 pmol/mg protein/30 min respectively in control, LATS and TSH-treated animals) without a demonstrable change in the apparent Km (approximately 2.0 microM for T4). The present study demonstrated that some LATS-rich sera stimulate thyroid T4 to T3 conversion in mouse. It provides an insight into the mechanism of increased T3 secretion from Graves' thyroid glands.

Activation of thyroid adenyl cyclase by antisera to thyroid plasma membrane preparations: Effects of IgG and non-IgG antiserum components

We have previously shown that IgG isolated from rabbit antibovine thyroid plasma membrane (anti-BTPM) antibodies exhibits properties similar to long acting thyroid stimulator (LATS) and HTS-Ig in that it activates thyroid adenyl cyclase. In order to test whether another immunoglobulin class, eg. IgM, of anti-BTPM antiserum can also stimulate the bovine thyroid adenyl cyclase system, protein molecules of the antiserum were separated into different molecular sizes by gel filtration chromatography on Sephadex G-200. It was observed that the low molecular weight fraction, consisting predominantly of albumin, was inactive in stimulating adenyl cyclase of the thyroid gland. In contrast, both IgM-enriched and IgG-enriched fractions of the immune serum were fully active. Furthermore, the thyroid-stimulating activity of the IgM-enriched fraction can only be inhibited by anti-IgM and that of the IgG-enriched fraction by anti-IgG. Our data suggest that IgM, in addition to IgG, may also have LATS or LATS-like activities in terms of activating adenyl cyclase of the thyroid gland.

Pretibial Myxedema Associated With Chronic Thyroiditis

To the Editor.— Pretibial myxedema (PM) is sometimes seen in the patients with thyroid dysfunction, most commonly Graves' disease. 1 I report herein a case of pretibial myxedema that was observed in a patient with chronic lymphocytic thyroiditis. Report of a Case.— A 43-year-old woman was noted to have slowly growing skin eruptions on the lower part of the legs in June 1981. Physical examination revealed reddish plaques with an orangepeellike appearance and coarse hairs on her both legs, mild exophthalmos with periorbital edema, clubbed fingers, and diffuse goiter. Routine laboratory test results were within normal limits, except for high titer of antimicrosomal antibody. Longacting thyroid stimulator was absent. Several thyroid function tests revealed a pattern of hyperthyroidism. Histology of the skin lesion showed dense mucin deposition in the middle and lower dermis stained with toluidine blue solution, the mucin was digested with testicular hyaluronidase. A thyroid biopsy specimen revealed

Characterization of thyroid-stimulating immunoglobulin-induced cyclic AMP accumulation in the rat thyroid cell strain FRTL-5: potentiation by forskolin and calibration against reference preparations of thyrotrophin.

A clonal strain of rat thyroid cells (FRTL-5) has been used to investigate the biological activity of a Research Standard preparation of long-acting thyroid stimulator (LATS-B). Using the accumulation of intracellular cyclic AMP as a response parameter, significant stimulation was attained at a LATS-B dose of 0.75 mu./ml. The inter-bioassay coefficient of variation in response to a fixed dose of LATS-B (1.25 mu./ml) was 20.5%, as determined using eight sequential subcultures. Cells cultured directly from frozen stocks responded to both bovine TSH and LATS-B in a manner indistinguishable from cells subjected to regular subculturing. Cyclic AMP responses to incremental doses of LATS-B were potentiated after the inclusion of a low dose of forskolin (0.1 mumol/l). However, forskolin addition had no effect on the time-course of LATS-B-stimulated cyclic AMP accumulation, half-maximal responses being attained after 60 min in either the presence or absence of the diterpene. In the presence of 0.1 mumol forskolin/l, intracellular cyclic AMP responses to LATS-B were demonstrably parallel with those to human TSH (Second International Reference Preparation, 80/558), whilst parallel incremental cyclic AMP responses were also observed in respect of TSH and serial dilutions of a potent thyroid-stimulating immunoglobulin (TSIg) preparation, indicating that for this particular Graves' disease patient, TSIg bioactivity may be expressed in terms of a convenient and reproducible standard, as TSH microunit equivalents.

Characterization of monoclonal antibodies raised against solubilized thyrotropin receptors in a cytochemical bioassay for thyroid stimulators.

Selected clones of monoclonal antibodies from mice immunized with solubilized preparations of bovine TSH receptors have been characterized in a cytochemical bioassay (CBA) for thyroid stimulators. This assay is based upon quantification of changes in naphthylamidase activity of sections of guinea pig thyroids with use of a chromogenic substrate. Monoclonal 22A6 is a thyroid-stimulating antibody directed at a site within the TSH receptor. Thus, although it is a weak inhibitor of 125I-TSH binding to thyroid membranes, 22A6 is inhibited from binding to membranes by TSH, exhibits a more than additive agonist effect on adenylate cyclase activity when tested at low TSH concentrations in thyroid cells, and is a competitive antagonist of TSH enhancement of adenylate cyclase activity at high TSH concentrations. In the CBA, 22A6 is a stimulator whose maximal activity is obtained with 77 pg/ml (3-min exposure). Dose-response curves of a long acting thyroid stimulator (LATS)-B standard and 22A6 have slopes which are not significantly different; as anticipated, the response to LATS-B is inhibited by antihuman immunoglobulin G (IgG) and that due to 22A6 by antimouse IgG. In contrast to 22A6, monoclonal 11E8 is a relatively potent inhibitor of 125I-TSH binding as well as TSH stimulation of adenylate cyclase activity, while failing to act as a stimulator itself. 11E8 is itself inactive as a stimulator in the CBA over a wide dose range; it does, however, inhibit TSH stimulation in the CBA. This inhibition is abolished by antimouse IgG. The transient peak of response observed in time courses to TSH occurs later in the presence of 11E8. Unlike its effect on TSH 11E8 shows relatively low potency (greater than 10,000-fold lower) when inhibiting stimulation by the thyroid stimulating antibodies, 22A6 or LATS-B. Since this difference cannot be explained by quantitative differences in the ability of 22A6 or 11E8 to bind to thyroid membranes, the CBA data suggest that the stimulating antibodies, 22A6 and LATS-B, may interact with different determinants on TSH receptors then either TSH or the blocking antibody, 11E8. This also implies that in Graves' disease blocking antibodies may be incompletely expressed in the presence of stimulating antibodies, although they may be potent inhibitors of TSH binding, as measured in receptor assays.

Effects of in vivo triiodothyronine and long acting thyroid stimulator (LATS) administration on the vitro thyroid cAMP response to thyrotrophin and LATS.

The present study was undertaken to examine the effects of prolonged in vivo treatment with T3 and long acting thyroid stimulator (LATS) on in vitro responsiveness of mouse thyroid cyclic AMP to thyrotrophin (TSH) and LATS-immunoglobulin G (IgG). In control mice, thyroid cAMP concentrations after incubation with normal-IgG (10 mg/ml) for 2 h, TSH (10 mU/ml) for 10 min and LATS-IgG (10 mg/ml) for 2 h were 1.25 +/- 0.11 (mean +/- SE) (n = 5), 15.87 +/- 3.47 (n = 6) and 2.17 +/- 0.25 pmoles/mg wet weight (n = 6), respectively. In mice given T3 (5 micrograms/ml) in drinking water for 5 days, thyroid cAMP concentrations after an incubation with TSH were reduced by 50%, as compared to those of the control mice. They were also decreased in mice injected ip with 5 mg of LATS-IgG (1000%/5 mg in the McKenzie bioassay) daily for 5 days. Combined treatment with T3 and LATS decreased the cAMP response to TSH only to the same extent as did T3 alone, indicating that the inhibitory effects of T3 and LATS were not additive. Similar findings were observed with the thyroid cAMP response to LATS-IgG in vitro; either T3 or LATS treatment in vivo decreased cAMP response to LATS-IgG in vitro, but combined treatment with T3 and LATS did not cause further inhibition as compared with T3 or LATS treatment alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum long acting thyroid stimulator (LATS) and LATS-protector (LATS-P) in Graves' disease associated with localized myxedema.

When localized myxedema occurs in Graves' disease, there is often very high serum long acting thyroid stimulator (LATS) activity. However, this association is not invariable and no pathogenetic role for this IgG associated activity is known. Serum LATS protector (LATS-P) is a closely related IgG activity which is present in the majority of cases of untreated Graves' disease. It usually coexists in LATS positive sera in a substantially greater concentration. Its association with localized myxedema has not been studied, nor have serial studies been performed on this activity during the clinical course of the disease. Fourteen patients (13 females, 1 male) with localized myxedema and a history of Graves' disease were examined. In 13 serum LATS was detectable with a wide range of activity from 2.4 to 1,000 units/ml. Serum LATS-P was detected in all including the LATS negative patient with a range of activity from 46 to 4,068 units/ml. Serial studies for at least 2 years were conducted in 8 patients. In two there was no change in either skin lesions or in serum LATS and LATS-P. In 6 the skin lesions partially or completely resolved. In 5 this was associated with statistically significant falls in serum LATS and LATS-P but in one no significant change occurred. The study demonstrated the high prevalence of LATS and LATS-P in localized myxedema. In the sole LATS negative patient there was a high concentration of LATS-P. The role of these activities in the pathogenesis of the disease remains unknown but in serial studies falls in activity were usually associated with clinical improvement.

A water-soluble fragment of the thyroid-stimulating hormone receptor which binds both thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies.

Previous studies have shown that freezing and thawing of human thyroid homogenates releases a water-soluble substance which reversibly binds to TSH-receptor antibodies. This substance has been designated long-acting thyroid stimulator absorbing activity (LAA). We now describe a new method for measuring LAA based on the TSH-receptor assay and application of the technique to the study of LAA. Our results indicate that LAA is a heat-labile glycoprotein which co-elutes with haemoglobin on gel filtration. Furthermore, LAA is retarded by columns of Sepharose-TSH but not by Sepharose coupled to human chorionic gonadotrophin, normal immunoglobulin G or bovine serum albumin, suggesting that LAA contains a binding site for TSH as well as for TSH-receptor antibodies. It would seem therefore that LAA is a water-soluble fragment of the TSH receptor possibly resulting from proteolytic cleavage of the receptor at a site close to the cell surface.

A hydrophilic fragment of the thyrotropin receptor

Conference Article| December 01 1983 A hydrophilic fragment of the thyrotropin receptor EIRIAN DAVIES JONES; EIRIAN DAVIES JONES 1Endocrine Immunology Unit, Department of Medicine, Welsh National School of Medicine, Cardiff CF4 4XN, Wales, U.K. Search for other works by this author on: This Site PubMed Google Scholar ROGER D. HOWELLS; ROGER D. HOWELLS 1Endocrine Immunology Unit, Department of Medicine, Welsh National School of Medicine, Cardiff CF4 4XN, Wales, U.K. Search for other works by this author on: This Site PubMed Google Scholar CAROLE R. RICKARDS; CAROLE R. RICKARDS 1Endocrine Immunology Unit, Department of Medicine, Welsh National School of Medicine, Cardiff CF4 4XN, Wales, U.K. Search for other works by this author on: This Site PubMed Google Scholar PAUL R. BUCKLAND; PAUL R. BUCKLAND 1Endocrine Immunology Unit, Department of Medicine, Welsh National School of Medicine, Cardiff CF4 4XN, Wales, U.K. Search for other works by this author on: This Site PubMed Google Scholar BERNARD REES SMITH BERNARD REES SMITH 1Endocrine Immunology Unit, Department of Medicine, Welsh National School of Medicine, Cardiff CF4 4XN, Wales, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1983) 11 (6): 751–753. https://doi.org/10.1042/bst0110751 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation EIRIAN DAVIES JONES, ROGER D. HOWELLS, CAROLE R. RICKARDS, PAUL R. BUCKLAND, BERNARD REES SMITH; A hydrophilic fragment of the thyrotropin receptor. Biochem Soc Trans 1 December 1983; 11 (6): 751–753. doi: https://doi.org/10.1042/bst0110751 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: LATS, long-acting thyroid stimulator, LAA, LATS-absorbing activity This content is only available as a PDF. © 1983 Biochemical Society1983 Article PDF first page preview Close Modal You do not currently have access to this content.