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Linsitinib Decreases Thyrotropin-Induced Thyroid Hormone Synthesis by Inhibiting Crosstalk Between Thyroid-Stimulating Hormone and Insulin-Like Growth Factor 1 Receptors in Human Thyrocytes and in Mice.
Thyroid
December 2024
Laboratory of Endocrinology and Receptor Biology, Bethesda, Maryland, USA.
Thyrotropin receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) have been shown to crosstalk in primary cultures of human thyrocytes (hThyros) and Graves' orbital fibroblasts. The phenomenon of TSHR/IGF-1R crosstalk has been largely studied in the pathogenesis of thyroid eye disease (TED) in human orbital fibroblasts. Here, we investigated the effects of inhibiting the IGF-1R-mediated contribution to crosstalk by linsitinib (Lins), a small-molecule IGF-1R kinase inhibitor, on TSH-induced regulation of thyroperoxidase (TPO) and thyroglobulin (TG) mRNAs and proteins in hThyros and on TPO and TG mRNAs and free thyroxine (fT4) levels in mice.
View Article and Find Full Text PDFCharacterization of a human thyroid microtissue model for testing thyroid disrupting chemicals.
Front Toxicol
July 2024
Research and Development, LifeSciences Division, LifeNet Health, Research Triangle Park, NC, United States.
Perturbation of thyroid hormone (T) synthesis is known to cause numerous developmental, metabolic, and cognitive disorders in humans. Due to species differences in sensitivity to chemical exposures, there is a need for human-based approaches that recapitulate thyroid cellular architecture and T production when screening. To address these limitations, primary human thyrocytes, isolated from healthy adult donor tissues and cryopreserved at passage one (p'1) were characterized for cellular composition, 3D follicular architecture, and thyroglobulin (TG)/T expression and inhibition by prototype thyroid disrupting chemicals (TDC).
View Article and Find Full Text PDFRecombinant Human TSH Fails to Induce the Proliferation and Migration of Papillary Thyroid Carcinoma Cell Lines.
Cancers (Basel)
July 2024
Endocrine Division, Department of Internal Medicine, School of Medicine, University of Patras, 26504 Patras, Greece.
Thyrotropin (TSH) suppression is required in the management of patients with papillary thyroid carcinoma (PTC) to improve their outcomes, inevitably causing iatrogenic thyrotoxicosis. Nevertheless, the evidence supporting this practice remains limited and weak, and in vitro studies examining the mitogenic effects of TSH in cancerous cells used supraphysiological doses of bovine TSH, which produced conflicting results. Our study explores, for the first time, the impact of human recombinant thyrotropin (rh-TSH) on human PTC cell lines (K1 and TPC-1) that were transformed to overexpress the thyrotropin receptor (TSHR).
View Article and Find Full Text PDFHighly Effective Synthetic Polymer-Based Blockers of Non-Specific Interactions in Immunochemical Analyses.
Polymers (Basel)
March 2024
Institute of Macromolecular Chemistry, Academy of Sciences, Heyrovského nám 2, 160 00 Prague, Czech Republic.
In vitro diagnostic methods face non-specific interactions increasing their background level and influencing the efficacy and reproducibility. Currently, the most important and employed blocker of non-specific interactions is bovine serum albumin (BSA), an animal product with some disadvantages like its batch-to-batch variability and contamination with RNases. Herein, we developed amphiphilic water-soluble synthetic copolymers based on the highly biocompatible, non-immunogenic and nontoxic -2-(hydroxypropyl)methacrylamide (HPMA)-based copolymers or poly(oxazoline)s as highly effective synthetic blockers of non-specific interactions and an effective BSA alternative.
View Article and Find Full Text PDFInvestigations on some indicators in the blood of cattle with orosthenic activity tongue rolling.
J Adv Vet Anim Res
June 2023
Department of Internal Medicine, Faculty of Veterinary Medicine, Trakia University, Stara Zagora, Bulgaria.
Objective: Hematological studies were carried out in cattle with tongue-rolling hyperactivity in order to establish the etiopathogenetic mechanisms of this behavioral disorder.
Materials And Methods: Cattle were divided into two groups: Group 1 ( 12), control animals that did not demonstrate the tongue-rolling orosthenic activity, and Group 2 ( 12), cattle that manifested this stereotyped behavior. Blood samples were collected from all cattle twice at 10-day intervals from for analysis of red blood cell counts, hemoglobin (HGB) content, mean corpuscular volume (MCV), mean corpuscular HGB (MCH), mean corpuscular HGB concentration (MCHC), hematocrit (HCT), white blood cell counts (WBC), and differential white cell counts [lymphocytes (LYM), monocytes (MON), and granulocytes (GRAs)].
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