scholarly journals The Effect of TSH-Suppressive Dose of Levothyroxine On Skeletal Muscle In Ovariectomized Rats

2021 ◽  
Author(s):  
Jeong Hun Kim ◽  
Ji Min Kim ◽  
Byung-Joo Lee ◽  
In-Joo Kim ◽  
Kyoungjune Pak ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Nodular Goiter ◽  
Thyroid Stimulating Hormone ◽  
Ovariectomized Rats ◽  
Suppressive Therapy ◽  
Mrna Levels ◽  
Hormonal Changes ◽  
Sprague Dawley ◽  
Toxic Nodular Goiter

Abstract Hyperthyroidism is often observed in postmenopausal women due to conditions such as thyroiditis and toxic nodular goiter, Grave’s disease or thyroid stimulating hormone suppressive therapy for treating differentiated thyroid carcinoma (DTC). However, the effect of such hormonal changes on skeletal muscles in females remain unclear. Therefore, this study aimed to observe the effects of hyperthyroidism on the skeletal muscle of ovariectomized rats. We randomly divided female Sprague-Dawley rats into sham-operated (Sham), ovariectomized (OVX), and levothyroxine-treated ovariectomized groups (OVX+LT4). Levothyroxine was administered intraperitoneally at 0.3 mg/kg, daily for six weeks. Protein synthesis was increased after ovariectomy whereas protein synthesis was suppressed and protein degradation was increased in response to levothyroxine treatment. However, there was no difference in lean mass between the two groups. Collagen I levels were similar between the Sham and OVX groups, but were significantly decreased in the OVX+LT4 group. The mRNA levels of matrix metalloproteinase (MMP) ‐2 and ‐9 were similar between the Sham and OVX groups but were upregulated in the OVX+LT4 group. After ovariectomy, mitochondrial biogenesis and dynamics were changed; these changes were exacerbated in hyperthyroidism. Our findings indicate that in postmenopausal rats with hyperthyroidism, the progression of muscle weakness occurs through impaired regulation of signaling pathways related to extracellular matrix homeostasis, protein turnover, and mitochondrial quality.

scholarly journals The Effects of Exogenous Lactate Administration on the IGF1/Akt/mTOR Pathway in Rat Skeletal Muscle

2020 ◽  
Vol 17 (21) ◽  
pp. 7805
Author(s):  
Sunghwan Kyun ◽  
Choongsung Yoo ◽  
Hun-Young Park ◽  
Jisu Kim ◽  
Kiwon Lim
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Expression ◽  
Lactate Concentration ◽  
Ring Finger ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Expression Levels ◽  
Igf Receptor

We investigated the effects of oral lactate administration on protein synthesis and degradation factors in rats over 2 h after intake. Seven-week-old male Sprague–Dawley rats were randomly divided into four groups (n = 8/group); their blood plasma levels of lactate, glucose, insulin, and insulin-like growth factor 1 (IGF1) were examined following sacrifice at 0, 30, 60, or 120 min after sodium lactate (2 g/kg) administration. We measured the mRNA expression levels of protein synthesis-related genes (IGF receptor, protein kinase B (Akt), mammalian target of rapamycin (mTOR)) or degradation-related genes (muscle RING-finger protein-1 (MuRF1), atrogin-1) and analyzed the protein expression and phosphorylation (activation) of Akt and mTOR. Post-administration, the plasma lactate concentration increased to 3.2 mmol/L after 60 min. Plasma glucose remained unchanged throughout, while insulin and IGF1 levels decreased after 30 min. The mRNA levels of IGF receptor and mTOR peaked after 60 min, and Akt expression was significantly upregulated from 30 to 120 min. However, MuRF1 and atrogin-1 expression levels were unaffected. Akt protein phosphorylation did not change significantly, whereas mTOR phosphorylation significantly increased after 30 min. Thus, lactate administration increased the mRNA and protein expression of protein-synthesis factors, suggesting that it can potentially promote skeletal muscle synthesis.

scholarly journals Intergenic bidirectional promoter and cooperative regulation of the IIx and IIb MHC genes in fast skeletal muscle

2008 ◽  
Vol 295 (1) ◽  
pp. R208-R218 ◽  
Author(s):  
Chiara Rinaldi ◽  
Fadia Haddad ◽  
Paul W. Bodell ◽  
Anqi X. Qin ◽  
Weihua Jiang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Antisense Rna ◽  
Bidirectional Promoter ◽  
Regulatory Elements ◽  
Feedback Mechanism ◽  
Medial Gastrocnemius ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Dynamic Regulation ◽  
Mhc Genes

This study investigated the dynamic regulation of IIx-IIb MHC genes in the fast white medial gastrocnemius (WMG) muscle in response to intermittent resistance exercise training (RE), a model associated with a rapid shift from IIb to IIx expression ( 11 ). We investigated the effect of 4 days of RE on the transcriptional activity across the skeletal MHC gene locus in the WMG in female Sprague-Dawley rats. Our results show that RE resulted in significant shifts from IIb to IIx observed at both the pre-mRNA and mRNA levels. An antisense RNA (xII NAT) was detected in the intergenic (IG) region between IIx and IIb, extending across the entire IIx gene and into its promoter. The expression of the xII NAT was positively correlated with IIb pre-mRNA ( R = +0.8), and negatively correlated with IIx pre-mRNA ( R = −0.8). Transcription mapping of the IIx–IIb IG region revealed the generation of sense IIb and xII NATs from a single promoter region. This bidirectional promoter is highly conserved among species and contains several regulatory elements that may be implicated in its regulation. These results suggest that the IIx and the IIb genes are physically and functionally linked via the bidirectional promoter. In order for the IIx MHC gene to be regulated, a feedback mechanism from the IG xII NAT is needed. In conclusion, the IG bidirectional promoter generating antisense RNA appears to be essential for the coordinated regulation of the skeletal muscle MHC genes during dynamic phenotype shifts.

scholarly journals The mTORC1 signaling repressors REDD1/2 are rapidly induced and activation of p70S6K1 by leucine is defective in skeletal muscle of an immobilized rat hindlimb

2013 ◽  
Vol 304 (2) ◽  
pp. E229-E236 ◽  
Author(s):  
Andrew R. Kelleher ◽  
Scot R. Kimball ◽  
Michael D. Dennis ◽  
Rudolf J. Schilder ◽  
Leonard S. Jefferson
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Molecular Mechanisms ◽  
Bed Rest ◽  
Disuse Atrophy ◽  
Sprague Dawley ◽  
Ribosomal Protein S6 ◽  
Sprague Dawley Rats ◽  
Mtorc1 Signaling ◽  
Limb Immobilization

Limb immobilization, limb suspension, and bed rest cause substantial loss of skeletal muscle mass, a phenomenon termed disuse atrophy. To acquire new knowledge that will assist in the development of therapeutic strategies for minimizing disuse atrophy, the present study was undertaken with the aim of identifying molecular mechanisms that mediate control of protein synthesis and mechanistic target of rapamycin complex 1 (mTORC1) signaling. Male Sprague-Dawley rats were subjected to unilateral hindlimb immobilization for 1, 2, 3, or 7 days or served as nonimmobilized controls. Following an overnight fast, rats received either saline or l-leucine by oral gavage as a nutrient stimulus. Hindlimb skeletal muscles were extracted 30 min postgavage and analyzed for the rate of protein synthesis, mRNA expression, phosphorylation state of key proteins in the mTORC1 signaling pathway, and mTORC1 signaling repressors. In the basal state, mTORC1 signaling and protein synthesis were repressed within 24 h in the soleus of an immobilized compared with a nonimmobilized hindlimb. These responses were accompanied by a concomitant induction in expression of the mTORC1 repressors regulated in development and DNA damage responses (REDD) 1/2. The nutrient stimulus produced an elevation of similar magnitude in mTORC1 signaling in both the immobilized and nonimmobilized muscle. In contrast, phosphorylation of 70-kDa ribosomal protein S6 kinase 1 (p70S6K1) on Thr229 and Thr389 in response to the nutrient stimulus was severely blunted. Phosphorylation of Thr229 by PDK1 is a prerequisite for phosphorylation of Thr389 by mTORC1, suggesting that signaling through PDK1 is impaired in response to immobilization. In conclusion, the results show an immobilization-induced attenuation of mTORC1 signaling mediated by induction of REDD1/2 and defective p70S6K1 phosphorylation.

Hypothyroidism and Thyrotoxicosis

2019 ◽  
Author(s):  
Paul W. Ladenson
Keyword(s):  
Thyroid Tissue ◽  
Elevated Serum ◽  
Nodular Goiter ◽  
Thyroid Stimulating Hormone ◽  
Graves Disease ◽  
Thyroid Function Tests ◽  
Toxic Nodular Goiter ◽  
Total Thyroxine ◽  
Characteristic Features ◽  
Toxic Goiter

Thyroid disorders are the most common endocrine conditions encountered in clinical practice and can range from clinically obvious to clinically silent. This review provides the definition and epidemiology of the conditions of hypothyroidism and hyperthyroidism. Hypothyroidism can be congenital or acquired, and its pathogenesis, diagnosis, and management are presented. The three most common disorders of thyrotoxicosis (diffuse toxic goiter [Graves disease], toxic nodular goiter, and iatrogenic thyrotoxicosis in thyroid hormone–treated patients are addressed, as well as the many diseases in each of these categories. This review also discusses thyroiditis, goiter, thyroid nodules, and thyroid cancer. Tables list the causes of elevated serum thyroid-stimulating hormone (TSH) levels, the etiologic classification of thyrotoxicosis, characteristic features of thyroiditis, and causes of elevated serum total thyroxine levels. Figures show the prevalence of abnormalities in thyroid function tests in different populations, certain forms of hyperthyroidism that result from pathophysiologic activation of the TSH receptor, and inflammation of thyroid tissue in acute thyroiditis.   This review contains 3 figures, 12 tables, and 61 references. Key Words: Hypothyroidism, Thyrotoxicosis, Thyrotropin, celiac disease, vitiligo, pernicious anemia, Sjögren syndrome, Graves disease, Munchausen syndrome

Effect of ovarian hormones on mitochondrial enzyme activity in the fat oxidation pathway of skeletal muscle

2001 ◽  
Vol 281 (4) ◽  
pp. E803-E808 ◽  
Author(s):  
S. E. Campbell ◽  
M. A. Febbraio
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Maximal Activity ◽  
Ovariectomized Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Muscle Enzyme ◽  
Sprague Dawley Rats ◽  
Oxidative Pathway ◽  
17Β Estradiol

To examine the roles of 17β-estradiol (E2) and progesterone (Prog) in lipid metabolism, skeletal muscle enzyme activities were studied in female Sprague-Dawley rats. Groups included sham-operated rats (C) and ovariectomized rats treated with placebo (O), E2 (E), Prog (P), both hormones at physiological doses (P + E), or both hormones with a high dose of E2 (P + HiE). Hormone (or vehicle only) delivery was via time-release pellets inserted at the time of surgery, 15 days before metabolic testing. Results demonstrated that carnitine palmitoyltransferase maximal activity was 19, 21, and 19% lower ( P < 0.01) in O, P, and P + E rats, respectively, compared with C rats. Conversely, activity in E and P + HiE rats was 14 and 19% higher ( P < 0.01) than in C. β-Hydroxyacyl-CoA dehydrogenase (β-HAD) maximal activity was 20% lower ( P < 0.01) in O than in C rats; similarly, P and P + E rats were 18 and 19% lower, respectively ( P < 0.01); however, treatment with E2returned β-HAD activity to C levels. These results suggest that E2 plays a role in lipid metabolism by increasing the maximal activity of key enzymes in the fat oxidative pathway of skeletal muscle.

scholarly journals Effect of the Lipoxygenase Inhibitor Baicalein on Muscles in Ovariectomized Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
D. Saul ◽  
J. H. Kling ◽  
R. L. Kosinsky ◽  
D. B. Hoffmann ◽  
M. Komrakova ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Fibre Diameter ◽  
Serum Creatine Kinase ◽  
Ovariectomized Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Lipoxygenase Inhibitor ◽  
Sprague Dawley Rats ◽  
Inflammatory Effect

Sarcopenia, a loss of muscle mass accompanying osteoporosis, leads to falls and fall-related injuries. Baicalein, as a phytochemical agent, has an antioxidative and anti-inflammatory effect in muscle. In this study, sixty-one female Sprague Dawley rats were divided into five groups: four groups were ovariectomized (OVX) and one control group was nonovariectomized (NON-OVX). Eight weeks after ovariectomy, three disparate concentrations (1 mg/kg body weight (BW), 10 mg/kg BW, and 100 mg/kg BW) of baicalein were applied subcutaneously daily in three OVX groups. Mm. soleus, gastrocnemius, and longissimus were extracted; their diameter, area, relation to body, and muscle weights as well as number of capillaries per fibre were recorded. In Mm. soleus and gastrocnemius, the baicalein effect (increasing number of capillaries per fibre) was proportional to the dose applied. The fibre diameters and area under baicalein treatment were significantly greater compared to OVX and NON-OVX groups. In M. longissimus, we observed a shift to type IIa fibres. Serum creatine kinase levels were significantly lower in highest baicalein concentration group. We conclude that baicalein can stimulate angiogenesis, though not fibre type-specific, in skeletal muscle and reduce the estrogen-related loss of fibre diameter and area in the skeletal muscle in rats. Therefore, a protective effect of baicalein on muscle cells can be assumed.

USP19-deubiquitinating enzyme regulates levels of major myofibrillar proteins in L6 muscle cells

2009 ◽  
Vol 297 (6) ◽  
pp. E1283-E1290 ◽  
Author(s):  
Priyanka Sundaram ◽  
Zhiyu Pang ◽  
Miao Miao ◽  
Lu Yu ◽  
Simon S. Wing
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Troponin T ◽  
Fold Increase ◽  
Muscle Cells ◽  
Deubiquitinating Enzyme ◽  
Myofibrillar Proteins ◽  
Mrna Levels ◽  
L6 Muscle Cells

The ubiquitin-proteasome system plays an important role in the degradation of myofibrillar proteins that occurs in muscle wasting. Many studies have demonstrated the importance of enzymes mediating conjugation of ubiquitin. However, little is known about the role of deubiquitinating enzymes. We previously showed that the USP19-deubiquitinating enzyme is induced in atrophying skeletal muscle (Combaret L, Adegoke OA, Bedard N, Baracos V, Attaix D, Wing SS. Am J Physiol Endocrinol Metab 288: E693–E700, 2005). To further explore the role of USP19, we used small interfering RNA (siRNA) in L6 muscle cells. Lowering USP19 by 70–90% in myotubes resulted in a 20% decrease in the rate of proteolysis and an 18% decrease in the rate of protein synthesis, with no net change in protein content. Despite the decrease in overall synthesis, there were ∼1.5-fold increases in protein levels of myosin heavy chain (MHC), actin, and troponin T and a ∼2.5-fold increase in tropomyosin. USP19 depletion also increased MHC and tropomyosin mRNA levels, suggesting that this effect is due to increased transcription. Consistent with this, USP19 depletion increased myogenin protein and mRNA levels approximately twofold. Lowering myogenin using siRNA prevented the increase in MHC and tropomyosin upon USP19 depletion, indicating that myogenin mediated the increase in myofibrillar proteins. Dexamethasone treatment lowered MHC and increased USP19. Depletion of USP19 reversed the dexamethasone suppression of MHC. These studies demonstrate that USP19 modulates transcription of major myofibrillar proteins and indicate that the ubiquitin system not only mediates the increased protein breakdown but is also involved in the decreased protein synthesis in atrophying skeletal muscle.

scholarly journals Radioiodine therapy outcome in toxic multinodular goiter patient with concomitant hereditary Hasharon hemoglobinopathy

2020 ◽  
Vol 66 (3) ◽  
pp. 27-32
Author(s):  
Dali S. Dzeytova ◽  
Stanislav S. Shklyaev ◽  
Pavel O. Rumyantsev ◽  
Marina S. Sheremeta ◽  
Alexey A. Trukhin ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Radioiodine Therapy ◽  
Nodular Goiter ◽  
Thyroid Stimulating Hormone ◽  
Drug Induced ◽  
Toxic Nodular Goiter ◽  
Toxic Multinodular Goiter ◽  
History Of ◽  
Abnormal Hemoglobin ◽  
Heterozygous Form

This research describes a clinical case of treatment of a patient with thyrotoxicosis with concomitant hematological pathology carriage of unstable hemoglobin Hasharon. A patient diagnosed with Diffuse toxic nodular goiter. Thyrotoxicosis of medium severity. Drug-induced hypothyroidism was admitted to the Department of radionuclide therapy for the purpose of treatment with radioactive iodine. Onset of disease - summer 2018 (thyroid-stimulating hormone (TSH) 0 mIU/ml). The instrumental studies (ultrasound, scintillation scanning of the thyroid gland) were performed at the pre-radioiodine therapy (RIT) diagnostic stage. The history of the disease indicates, that in 2000 the patient was suspected of having abnormal hemoglobin, since then no examinations have been conducted and anemia has never been detected. The diagnosis of ancestral hemoglobinopathy with the presence (17%) of unstable Hasharon-Sinai-Sealy hemoglobin in a heterozygous form was verified during the preparation to RIT. The radionuclide therapy I131 with activity of 400 MBq was performed on 02.07.2019. The monthly monitoring of laboratory and instrumental indicants was carried out during the post-therapeutic period: the state of hypothyroidism was reached by the end of 2 months after RT, no episodes of significant increase in bilirubin levels were observed during the observation period; no side effects from RT were stated. It becomes possible based on the example of the above observation, to judge the safety of conducting RT for treatment of thyrotoxicosis in patients with similar hemoglobinopathy, without excluding, however, the need for an individual approach in each case.

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