scholarly journals The Hinge Region of Human Thyroid-Stimulating Hormone (TSH) Receptor Operates as a Tunable Switch between Hormone Binding and Receptor Activation

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e40291 ◽  
Author(s):  
Ritankar Majumdar ◽  
Rajan R. Dighe
2008 ◽  
Vol 283 (26) ◽  
pp. 18048-18055 ◽  
Author(s):  
Sandra Mueller ◽  
Gunnar Kleinau ◽  
Holger Jaeschke ◽  
Ralf Paschke ◽  
Gerd Krause

1984 ◽  
Vol 100 (1) ◽  
pp. 113-118 ◽  
Author(s):  
E. Davies Jones ◽  
B. Rees Smith

ABSTRACT 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. J. Endocr. (1984) 100, 113–118


1994 ◽  
Vol 130 (1) ◽  
pp. 92-96 ◽  
Author(s):  
Masayoshi Yoshimura ◽  
A Eugene Pekary ◽  
Xuan-Ping Pang ◽  
Loretta Berg ◽  
Laurence A Cole ◽  
...  

Yoshimura M, Pekary AE, Pang X-P, Berg L, Cole LA, Kardana A, Hershman JM. Effect of peptide nicking in the human chorionic gonadotropin β-subunit on stimulation of recombinant human thyroid-stimulating hormone receptors. Eur J Endocrinol 1994;130:92–6. ISSN 0804–4643 It is now generally accepted that human chorionic gonadotropin (hCG) has thyroid-stimulating activity. Heterologous forms of the hCG molecule occur in the purified preparations extracted from urine of pregnant women and patients with trophoblastic diseases. This work was undertaken to determine the effect of peptide nicking in the hCG-β subunit on its thyrotropic potency. Using Chinese hamster ovary cells expressing functional human thyroid-stimulating hormone (TSH) receptors, we examined the effect of nicked hCG on cyclic AMP (cAMP) production and receptor binding. The effect of human leukocyte elastase (hLE), a nicking enzyme, on standard hCG also was examined in the cAMP assay and on receptor binding. We studied five hCG preparations extracted from the urine of normal pregnancy (CR-127 and P8) and trophoblastic diseases (C2, C5 and M4). Two preparations (C2, 96% nicked and M4, 100% nicked in the β44–49 region) showed about a 1.5-fold potency of standard hCG CR-127, which is also 20% nicked in the same region. Non-nicked hCG (P8) had the weakest potency among all of the samples tested. Treatment of standard hCG with hLE increased the cAMP response about two-fold. Dose-dependent displacement of bovine [125I]TSH by standard hCG and hLE-digested hCG was observed and was almost identical. We have confirmed the increased in vitro thyrotropic activity of hCG nicked in the β-intercysteine loop on recombinant human TSH receptors. These data suggest that peptide heterogeneity of the hCG molecule may modulate the in vivo thyrotropic activity of hCG in pregnant women and patients with trophoblastic diseases. Jerome M Hershman, Endocrinology-W111D, West Los Angeles VA Medical Center, Los Angeles, California 90073, USA


2015 ◽  
Vol 28 (5) ◽  
pp. 663
Author(s):  
Pedro Marques ◽  
Karim Chikh ◽  
Anne Charrié ◽  
Rosa Pina ◽  
Maria João Bugalho ◽  
...  

Thyroid-stimulating hormone-receptor autoantibodies normally causes hyperthyroidism. However, they might have blocking activity causing hypothyroidism. A 11-year-old girl followed due to type 1 diabetes mellitus, celiac disease and euthyroid lymphocytic thyroiditis at diagnosis. Two years after the initial evaluation, thyroid-stimulating hormone was suppressed with normal free T4; nine months later, a biochemical evolution to hypothyroidism with thyroid-stimulating hormone-receptor autoantibodies elevation was seen; the patient remained always asymptomatic. Chinese hamster ovary cells were transfected with the recombinant human thyroid-stimulating hormone -receptor, and then exposed to the patient´s serum; it was estimated a ‘moderate’ blocking activity of these thyroid-stimulating hormone-receptor autoantibodies, and concomitantly excluded stimulating action. In this case, the acknowledgment of the blocking activity of the serum thyroid-stimulating hormone-receptor autoantibodies, supported the hypothesis of a multifactorial aetiology of the hypothyroidism, which in the absence of the in vitro tests, we would consider only as a consequence of the destructive process associated to lymphocytic thyroiditis.


2007 ◽  
Vol 40 (12) ◽  
pp. 1661-1670 ◽  
Author(s):  
G.J. Paz-Filho ◽  
C.O. Mesa-Junior ◽  
M. Olandoski ◽  
L.C. Woellner ◽  
C.A. Goedert ◽  
...  

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