Mitochondrial And Myogenic Gene Expression Pathways Are Influenced By The Exercise Mimetic Formoterol In Human Myotubes

Background: Exercise is an effective treatment for establishing and maintaining skeletal muscle (SKM) health. The interconnected cascade of gene expression pathways related to myogenesis, mitochondrial homeostasis, and thyroid hormone metabolism are critical to SKM health. This in vitro study was conducted to investigate the effects of exercise mimetic (formoterol) stimulation on human SKM cell signaling during myogenesis, and to provide insight on potential targets for future studies exploring therapies for SKM atrophy.Methods: Human myoblasts were cultured and differentiated to evaluate the effects of exercise mimetic stimulation on gene expression during mid and late myogenesis. We characterized the expression of 24 genes related to myogenesis, mitochondrial biogenesis, thyroid hormone metabolism, and cellular homeostasis.Results: Formoterol stimulated the gene expression for SKM pathways related to mitochondrial biogenesis, thyroid metabolism, and cellular homeostasis. Additionally, formoterol resulted in a myogenic program that appears to favor prolonged myoblast proliferation and delayed myotube maturation.Conclusion: Robust, yet differential effects of exercise mimetic stimulation on gene expression during mid-myogenesis and at terminal differentiation were found. The results of our study support the groundwork for establishing further experiments utilizing exercise signaling as a therapeutic treatment in models targeting dysfunctional SKM cell growth.

PSVI-17 Dissimilarities in thyroid profiles and pregnancy rates in dairy cows with different polymorphic variants of the DIO1 gene

Thyroid hormones are implicated in regulation of the reproductive function in cattle. In turn, thyroid metabolism is determined by the activity of different types deiodinases. Our research was aimed to compare post-insemination thyroid profiles and pregnancy rates in dairy cows with different SNP genotypes in the deiodinase gene of the first type (DIO1). Thirty lactating Russian Black Pied cows were synchronized using the Ovsynch protocol and artificially inseminated (AI). Blood samples from the cows were collected on Days 0, 7, 14, 21, and 33 after AI. Hormonal levels in the serum were measured by ELISA. Pregnancy was confirmed by progesterone concentrations and ultrasonography. Genetic variants for the DIO1 gene were tested by RT-PCR and polymorphism at position 13149 (NC_037330) was found. The occurrence frequency of cows with genotypes CC, CG, and GG was 43.3, 33.3, and 23.3 %, respectively. A proportion of pregnant cows in the CC group was higher than in the CG group (84.6 vs. 40.0%, P < 0.05) and tended to be higher than in the GG group (42.9%). The concentration of triiodothyronine (T3) in the blood of CC animals did not change during the studied period, whereas that in CG animals decreased between Days 0 and 14 (from 1.60±0.21 to 1.10±0.22 nmol/L, P < 0.05). Concurrently, the T3 concentration on Day 0 was 1.4 times lower (P < 0.05) in the CC group than in the CG group. Furthermore, the level of reverse T3 on Day 7 in the GG group was 1.3 times higher (P < 0.05) than in the CC or CG groups. Thus, cows with DIO1 gene CC genotype have a higher reproductive ability than cows with CG or GG genotypes, which may be due to peculiarities of thyroid profiles during the first two weeks of pregnancy. The study was supported by Russian Ministry of Science and Higher Education (0445-2021-0004).

Gut Microbiome Alterations in Patients With Thyroid Nodules

Thyroid nodules are found in nearly half of the adult population. Accumulating evidence suggests that the gut microbiota plays an important role in thyroid metabolism, yet the association between gut microbiota capacity, thyroid nodules, and thyroid function has not been studied comprehensively. We performed a gut microbiome genome-wide association study in 196 patients with thyroid nodules and 283 controls by using whole-genome shotgun sequencing. We found that participants with high-grade thyroid nodules have decreased number of gut microbial species and gene families compared with those with lower grade nodules and controls. There are also significant alterations in the overall microbial composition in participants with high-grade thyroid nodules. The gut microbiome in participants with high-grade thyroid nodules is characterized by greater amino acid degradation and lower butyrate production. The relative abundances of multiple butyrate producing microbes are reduced in patients with high-grade thyroid nodules and the relative abundances of L-histidine metabolism pathways are associated with thyrotropin-releasing hormone. Our study describes the gut microbiome characteristics in thyroid nodules and a gut-thyroid link and highlight specific gut microbiota as a potential therapeutic target to regulate thyroid metabolism.

Tissue quantification of radioiodine thyroid uptake in humans by an isotopic imaging technique on slides

BACKGROUND: Thyroid metabolism involves iodine, which allows us to use radioactive iodine for diagnostic and therapy purposes. The efficiency of radioiodine therapy depends on several parameters; the ability of thyroid tissue to uptake radioactive iodine is one of them. OBJECTIVE: The objective of this work is to quantify the radioactive iodine uptake on thyroid tissue. METHODS: In this work, we developed a method to quantify the in vivo uptake of iodine-131 on sections of thyroid glands removed by thyroidectomies. We performed an analysis of histological sections of the thyroid tissue by beta imaging. We had the opportunity to quantify the fixed radioactivity and to analyze its distribution in the thyroid gland, thanks to the good spatial resolution available with the type of detector used. RESULTS: The results gave a high image resolution showing the heterogeneity of iodine-131 fixation by the thyroid tissue. We were able to quantify the tissue radioactivity in mega Becquerel (MBq) per volume unit. CONCLUSION: This work has shown that the direct quantification of the thyroid tissue uptake is possible using the beta imaging system.

Role of thyroid metabolism in vestibular vertigo

<p class="abstract"><strong>Background:</strong> Thyroid hormones play a role in the development and functioning of the inner ear. Therefore, it was hypothesized that a derangement in the thyroid hormone levels can affect the cochleo-vestibular system.</p><p class="abstract"><strong>Methods:</strong> The present study included 64 cases and 64 controls. All patients diagnosed with peripheral vertigo were enrolled into the study. All the subjects underwent thyroid function tests- serum T3, T4 and thyroid stimulating hormone (TSH). Free hormone levels were obtained in patients with subclinical hypo or hyperthyroidism. The data was analyzed using Independent sample t test. </p><p class="abstract"><strong>Results:</strong> Out of 64 cases only 10 patients showed altered thyroid values. Fifty-nine cases were diagnosed with benign paroxysmal positional vertigo (BPPV) out of which 9 (15%) had altered thyroid hormone levels. Among the control group, 12 were found to have deranged thyroid hormone levels.</p><p class="abstract"><strong>Conclusions:</strong> There is no association between functional thyroid hormone levels and BPPV. Therefore, altered thyroid metabolism has no role in the causation of vestibular dysfunction due to BPPV. However, in case of Meniere’s disease and Vestibular neuronitis further studies with large sample size are required to ascertain the role of functional thyroid hormones in producing vestibular symptoms.</p>

Single Nucleotide Polymorphisms in Thyroid Hormone Transporter Genes MCT8, MCT10 and Deiodinase DIO2 Contribute to Inter-Individual Variance of Executive Functions and Personality Traits

Thyroid hormones are modulators of cognitive functions, and changes in hormone levels affect intelligence, memory, attention and executive function. Single nucleotide polymorphisms (SNPs) of transporter proteins MCT8, MCT10 and deiodinase 2 (DIO2) influence thyroid metabolism and could therefore contribute to inter-individual variance of cognitive functions. This study investigates the influence of these SNPs using an extensive neuropsychological test battery. 656 healthy participants aged 18–39 years were genotyped for four SNPs: MCT8 (rs5937843 and rs6647476), MCT10 (rs14399) and DIO2 (rs225014) and underwent eleven different neuropsychological tests as well as four personality questionnaires. Test results were compared between homo- and heterozygous carriers and for the X-linked MCT8 additionally between men and women. Personality questionnaires revealed that Risk Seeking was reduced in homozygous T carriers and highest in homozygous C carriers of the DIO2 SNP and that both polymorphisms of MCT8 had an additive effect on Physical Aggression in men. Neuropsychological testing indicated that MCT10 affects nonverbal reasoning abilities, DIO2 influences working memory and verbal fluency and MCT8 influences attention, alertness and planning. This pilot study suggests an influence of polymorphisms in thyroid hormone transporter genes and deiodinase on cognitive domains and personality traits.

Role of thyroid dysimmunity and thyroid hormones in endometriosis

Endometriosis is characterized by the presence of ectopic endometrial cells outside the uterine cavity. Thyroid autoimmunity has been associated with endometriosis. This work investigated the potential pathophysiological link between endometriosis and thyroid disorders. Transcripts and proteins involved in thyroid metabolism are dysregulated in eutopic and ectopic endometrium of endometriotic patients, leading to resistance of ectopic endometrium to triiodothyronine (T3) action and local accumulation of thyroxine (T4). Thyroid-stimulating hormone (TSH) acts as a proliferative and prooxidative hormone on all endometria of endometriosis patients and controls, whereas T3 and T4 act to specifically increase ectopic endometrial cell proliferation and reactive oxygen species (ROS) production. Mouse studies confirmed the data gained in vitro since endometriotic implants were found to be bigger when thyroid hormones increased. A retrospective analysis of endometriosis patients with or without a thyroid disorder revealed an increased chronic pelvic pain and disease score in endometriotic patients with a thyroid disorder.