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The approaches to correct thyroid deficiency include replacement therapy with thyroid hormones (THs), but such therapy causes a number of side effects. A possible alternative is thyroid-stimulating hormone (TSH) receptor activators, including allosteric agonists. The aim of this work was to study the effect of ethyl-2-(4-(4-(5-amino-6-(-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]pyrimidin-4-yl)phenyl)--1,2,3-triazol-1-yl) acetate (TPY3m), a TSH receptor allosteric agonist developed by us, on basal and thyroliberin (TRH)-stimulated TH levels and the hypothalamic-pituitary-thyroid (HPT) axis in male rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes mellitus (T2DM).

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The toxicity of tris (2-butoxyethyl) phosphate (TBOEP) has been extensively investigated because of its prevalence in the environment. Nevertheless, the risk factors associated with maternal transmission are poorly understood. In this study, sexually mature female zebrafish were treated with TBOEP (0, 20, 100, and 500 μg/L) for 30 days and were mated with unexposed males.

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Association of diethylhexyl phthalate exposure with serum thyroid hormone levels: a systematic review and meta-analysis.

Am J Transl Res

December 2024

Department of Genetics and Endocrinology, Chengdu Women's and Children's Center Hospital, School of Medicine, University of Electronic Science and Technology of China Chengdu, Sichuan, China.

Objective: Evidence suggests that diethylhexyl phthalate (DEHP) may disrupt thyroid hormone homeostasis by targeting multiple components of the hypothalamic-pituitary-thyroid (HPT) axis, potentially harming human health. However, the relationship between DEHP exposure and thyroid function remains debated. We performed a meta-analysis to clarify the association between DEHP exposure and thyroid function.

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A weight of evidence review on the mode of action, adversity, and the human relevance of xylene's observed thyroid effects in rats.

Crit Rev Toxicol

January 2025

Product Stewardship, Science & Regulatory, Shell Global Solutions International B.V. The Hague, the Netherlands.

Xylene substances have wide industrial and consumer uses and are currently undergoing dossier and substance evaluation under Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) for further toxicological testing including consideration of an additional neurotoxicological testing cohort to an extended one-generation reproduction toxicity (EOGRT) study. New repeated dose study data on xylenes identify the thyroid as a potential target tissue, and therefore a weight of evidence review is provided to investigate whether or not xylene-mediated changes on the hypothalamus-pituitary-thyroid (HPT) axis are secondary to liver enzymatic induction and are of a magnitude that is relevant for neurological human health concerns. Multiple published studies confirm xylene-mediated increases in liver weight, hepatocellular hypertrophy, and liver enzymatic induction the oral or inhalation routes, including an increase in uridine 5'-diphospho-glucuronosyltransferase (UDP-GT) activity, the key step in thyroid hormone metabolism in rodents.

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Since the early discovery of QRFP43, intensive research has been primarily focused on its role in the modulation of food intake. As is widely recognised, the regulation of the body's energy status is a highly complex process involving numerous systems, hormones and neurotransmitters. Among the most important regulators of energy status, alongside the satiety and hunger centre located in the hypothalamus, is the HPT axis, which directly and indirectly affects the regulation of metabolism in all cells of the body.

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