scholarly journals Thyroid Stimulating Hormone Triggers Hepatic Mitochondrial Stress through Cyclophilin D Acetylation

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Xiaolei Wang ◽  
Jinbao Mao ◽  
Xinli Zhou ◽  
Qiu Li ◽  
Ling Gao ◽  
...  
Keyword(s):  
Elevated Serum ◽  
Thyroid Stimulating Hormone ◽  
Cyclophilin D ◽  
Mitochondrial Stress ◽  
Knockout Mouse Model ◽  
Cellular Reactive Oxygen Species ◽  
Underlying Mechanisms ◽  
And Function ◽  
Stimulating Hormone

Background & Aims. Oxidative stress-related liver diseases were shown to be associated with elevated serum thyroid stimulating hormone (TSH) levels. Mitochondria are the main source of cellular reactive oxygen species. However, the relationship between TSH and hepatic mitochondrial stress/dysfunction and the underlying mechanisms are largely unknown. Here, we focused on exploring the effects and mechanism of TSH on hepatic mitochondrial stress. Methods. As the function of TSH is mediated through the TSH receptor (TSHR), Tshr-/- mice and liver-specific Tshr knockout (LKO) mice were used in our study. The thyroid-specific Tshr knockout mouse model injected with TSH (TKO+TSH) was used as a mimic for subclinical hypothyroidism (SCH) patients. Hepatic mitochondrial stress and function were analyzed in these mouse models, and the expression of key genes involved in mitochondrial stress was measured. Results. A relatively lower degree of mitochondrial stress was observed in the livers of Tshr-/- mice and LKO mice than those of their littermate counterparts. TSH caused concentration- and time-dependent effects on mitochondrial stress and cyclophilin D (CypD) acetylation in hepatocytes in vitro. Microarray and RT-PCR analyses showed that Tshr-/- mice had much higher lncRNA-AK044604 expression than their littermate counterparts. The use of the AK044604 overexpression plasmid and SIRT1 agonist proved that TSH aggravates CypD acetylation and mitochondrial stress via lncRNA-AK044604 and SIRT1. An inhibitor of CypD acetylation, cyclosporine A, suppressed TSH-induced hepatic mitochondrial stress and dysfunction. Conclusions. TSH stimulates hepatic CypD acetylation through the lncRNA-AK044604/SIRT1/SIRT3 signaling pathway, indicating an essential role for TSH in mitochondrial stress in the liver.

scholarly journals Hipotiroidismo Associado a Anticorpos Anti-Receptor da Hormona TSH com Ação Bloqueadora Determinada In Vitro

2015 ◽  
Vol 28 (5) ◽  
pp. 663
Author(s):  
Pedro Marques ◽  
Karim Chikh ◽  
Anne Charrié ◽  
Rosa Pina ◽  
Maria João Bugalho ◽  
...  
Keyword(s):  
Hormone Receptor ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Thyroid Stimulating Hormone ◽  
Human Thyroid ◽  
In Vitro Tests ◽  
Lymphocytic Thyroiditis ◽  
Blocking Activity ◽  
Stimulating Hormone

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.

scholarly journals Approach to Subclinical Thyroid Diseas

1970 ◽  
Vol 26 (2) ◽  
pp. 91-96
Author(s):  
Satya Ranjan Sutradhar
Keyword(s):  
Subclinical Hypothyroidism ◽  
Thyroid Dysfunction ◽  
Hormone Level ◽  
Elevated Serum ◽  
Thyroid Stimulating Hormone ◽  
Good Evidence ◽  
Reference Ranges ◽  
Mineral Density ◽  
Asymptomatic Patients ◽  
Stimulating Hormone

Subclinical thyroid dysfunction is defined as an abnormal serum thyroid-stimulating hormone level and free thyroxine and triiodothyronine levels within their reference ranges. The prevalence of subclinical hyperthyroidism is about 2 percent. Subclinical hypothyroidism is found in approximately 4 to 8.5 percent of the population. Most national organizations recommend against routine screening of asymptomatic patients, but screening is recommended for high risk populations. The management of subclinical thyroid dysfunction is controversial. There is good evidence that subclinical hypothyroidism is associated with progression to overt disease. Patients with a serum thyroid-stimulating hormone level greater than 10 mIU/L have a higher incidence of elevated serum low density lipoprotein cholesterol concentrations; however, evidence is lacking for other associations. There is insufficient evidence that treatment of subclinical hypothyroidism is beneficial. A serum thyroid stimulating hormone level of less than 0.1 mIU/L is associated with progression to overt hyperthyroidism, atrial fibrillation, reduced bone mineral density, and cardiac dysfunction. There is little evidence that early treatment alters the clinical course. DOI: 10.3329/jbcps.v26i2.4187 J Bangladesh Coll Phys Surg 2008; 26: 91-96

scholarly journals CUSHING DISEASE MASQUERADING AS GLAUCOMA

2019 ◽  
Vol 5 (5) ◽  
pp. e290-e293
Author(s):  
Yumiko Tsushima ◽  
Lubna Bashir Munshi ◽  
Charit Taneja ◽  
Se-min Kim
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Case Reports ◽  
Elevated Serum ◽  
Serum Cortisol ◽  
Thyroid Stimulating Hormone ◽  
Pituitary Hormone ◽  
Cushing Disease ◽  
Corticosteroid Administration ◽  
Late Night ◽  
Stimulating Hormone

Objective: Glaucoma is a well-recognized side effect of corticosteroids. However, steroid-induced glaucoma typically refers to that caused by exogenous corticosteroid administration. Glaucoma secondary to endogenous overproduction of corticosteroids has only been reported in a few case reports. We aim to bring attention to glaucoma as a rare but important manifestation of endogenous hypercortisolism. Methods: Patient history, physical exam, laboratory results, and imaging studies were reviewed. Results: We report a case of glaucoma as the initial presentation of Cushing disease (CD). The patient was diagnosed with glaucoma 16 months prior to his endocrinology evaluation. At our initial encounter, the patient had a cushingoid appearance. Levels of 24-hour urinary cortisol and late-night salivary cortisol were elevated. Serum cortisol was not suppressed by 1 mg of dexamethasone overnight, but it was suppressed by 8 mg of dexamethasone. Adrenocorticotropic hormone was also elevated. All other pituitary hormone axes were unremarkable (thyroid-stimulating hormone, free thyroxine, follicle-stimulating hormone, luteinizing hormone, growth hormone, prolactin, and insulin-like growth factor). Pituitary magnetic resonance imaging suggested a small adenoma (2 to 3 mm); therefore, the patient underwent inferior petrosal sinus sampling. The results were consistent with CD. Transsphenoidal resection was performed and final pathology confirmed an adrenocorticotropic hormone-positive adenoma. Hypercortisolism and intraocular pressures improved after the surgery. Conclusion: Glaucoma can lead to irreversible blindness if left untreated or uncontrolled. However, endogenous hypercortisolism-induced glaucoma can be reversed with treatment of the underlying CD. Thus, heightened awareness of extraocular manifestations of secondary causes of glaucoma such as endogenous hypercortisolism is necessary in order to promote prompt evaluation and treatment.

scholarly journals Plants-Derived Neuroprotective Agents: Cutting the Cycle of Cell Death through Multiple Mechanisms

2017 ◽  
Vol 2017 ◽  
pp. 1-27 ◽  
Author(s):  
Taiwo Olayemi Elufioye ◽  
Tomayo Ireti Berida ◽  
Solomon Habtemariam
Keyword(s):  
Mechanisms Of Action ◽  
Neuroprotective Agents ◽  
Structural Class ◽  
Molecular Features ◽  
Amyotropic Lateral Sclerosis ◽  
Underlying Mechanisms ◽  
And Function ◽  
Lateral Sclerosis

Neuroprotection is the preservation of the structure and function of neurons from insults arising from cellular injuries induced by a variety of agents or neurodegenerative diseases (NDs). The various NDs including Alzheimer’s, Parkinson’s, and Huntington’s diseases as well as amyotropic lateral sclerosis affect millions of people around the world with the main risk factor being advancing age. Each of these diseases affects specific neurons and/or regions in the brain and involves characteristic pathological and molecular features. Hence, several in vitro and in vivo study models specific to each disease have been employed to study NDs with the aim of understanding their underlying mechanisms and identifying new therapeutic strategies. Of the most prevalent drug development efforts employed in the past few decades, mechanisms implicated in the accumulation of protein-based deposits, oxidative stress, neuroinflammation, and certain neurotransmitter deficits such as acetylcholine and dopamine have been scrutinized in great detail. In this review, we presented classical examples of plant-derived neuroprotective agents by highlighting their structural class and specific mechanisms of action. Many of these natural products that have shown therapeutic efficacies appear to be working through the above-mentioned key multiple mechanisms of action.

Syndrome of'inappropriate secretion of thyroid-stimulating hormone' by partial target organ resistance to thyroid hormones

1981 ◽  
Vol 97 (3) ◽  
pp. 361-368 ◽  
Author(s):  
J. Salmerón De Diego ◽  
C. Alonso Rodriguez ◽  
A. Salazar Orlando ◽  
P. Sanchez Garcia Cervigon ◽  
E. Caviola Mutazzi ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Elevated Serum ◽  
Pituitary Tumour ◽  
Thyroid Stimulating Hormone ◽  
Target Organ ◽  
Resistance To Thyroid Hormones ◽  
Serum Thyroid Hormone ◽  
Serum Tsh ◽  
Tsh Levels ◽  
Stimulating Hormone

Abstract. A 74 year old woman was found to have elevated serum thyroid-stimulating hormone (TSH) levels and elevated serum thyroid hormone levels, with clinical euthyroidism. There was no evidence of a pituitary tumour. TSH levels increased substantially during methimazole therapy. Administration of dexamethasone was followed by a prompt fall in serum TSH levels. Triiodothyronine (T3) was administered over a period of 20 days in doses from 25 μg to as much as 100 μg daily causing a rise in serum T3 above 700 ng/100 ml, a decline of T4 and a blunting of the response to thyrotrophinreleasing hormone (TRH), with normal metabolic responses (pulse rate, photomotogram, cholesterol). These results suggest that the patient's disorder is due to partial target organ resistance to thyroid hormones.

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