Physiochemical and nutritional evaluation of whole kumquat fruits powder and its protective effect on thyroid hormones and blood sugar levels in diabetic rats

The present study was conducted to evaluate the chemical composition, antioxidant activity and hypoglycemic effects of whole kumquat (Ku) powder in diabetic rats fed a high-fat-high-cholesterol (HFHC) diet. The antioxidant activities were evaluated using stable 1,1-diphenyl 2-picrylhydrazyl (DPPH) free radical scavenging method, 2,2´-azinobis (3-ethyl benzo thiazoline-6-sulphonic acid) radical cation (ABTS) and Ferric reducing antioxidant power (FRAP). Total phenolic content was (51.85 mg GAE/g) and total flavonoid content was (0.24 mg Cateachin Equivalent, CE/g). DPPH and ABTS values were 3.32 and 3.98 mg Trolox equivalent (TE)/g where FRAP value was 3.00 mM Fe2+/kg dry material. A total of 90 albino rats were used in the present study. Rats group were as follows: normal diet; normal treated (2, 4, and 6% Ku.), diabetic rats (non-treated), diabetic + HFHC diet (non-treated), HFHC (non-treated), Diabetic (treated), HFHC (treated) and Diabetic + HFHC (treated). The diets were followed for 8 weeks. Blood samples were collected at the end of the experiment. Serum glucose was recorded and thyroid hormones (T4, Thyroxine and T3, Triiodothyronine) were conducted. Diet supplemented with Kumquat at different concentrations have a hypoglycemic effect and improve the thyroid hormones of both diabetic rats and HFHC diabetic rats.

Vitamin D3 Treatment Alters Thyroid Functional Morphology in Orchidectomized Rat Model of Osteoporosis

Vitamin D plays an essential role in prevention and treatment of osteoporosis. Thyroid hormones, in addition to vitamin D, significantly contribute to regulation of bone remodeling cycle and health. There is currently no data about a possible connection between vitamin D treatment and the thyroid in the context of osteoporosis. Middle-aged Wistar rats were divided into: sham operated (SO), orchidectomized (Orx), and cholecalciferol-treated orchidectomized (Orx + Vit. D3; 5 µg/kg b.m./day during three weeks) groups (n = 6/group). Concentration of 25(OH)D in serum of the Orx + Vit. D3 group increased 4 and 3.2 times (p < 0.0001) respectively, compared to Orx and SO group. T4, TSH, and calcitonin in serum remained unaltered. Vit. D3 treatment induced changes in thyroid functional morphology that indicate increased utilization of stored colloid and release of thyroid hormones in comparison with hormone synthesis, to maintain hormonal balance. Increased expression of nuclear VDR (p < 0.05) points to direct, TSH independent action of Vit. D on thyrocytes. Strong CYP24A1 immunostaining in C cells suggests its prominent expression in response to Vit. D in this cell subpopulation in orchidectomized rat model of osteoporosis. The indirect effect of Vit. D on bone, through fine regulation of thyroid function, is small.

Thyroid hormones regulate cardiac repolarization and QT-interval related gene expression in hiPSC cardiomyocytes

Prolongation of cardiac repolarization (QT interval) represents a dangerous and potentially life-threatening electrical event affecting the heart. Thyroid hormones (THs) are critical for cardiac development and heart function. However, little is known about THs influence on ventricular repolarization and controversial effects on QT prolongation are reported. Human iPSC-derived cardiomyocytes (hiPSC-CMs) and multielectrode array (MEA) systems were used to investigate the influence of 3,3′,5-triiodo-l-Thyronine (T3) and 3,3′,5,5′-tetraiodo-l-Thyronine (T4) on corrected Field Potential Duration (FPDc), the in vitro analog of QT interval, and on local extracellular Action Potential Duration (APD). Treatment with high THs doses induces a significant prolongation of both FPDc and APD, with the strongest increase reached after 24 h exposure. Preincubation with reverse T3 (rT3), a specific antagonist for nuclear TH receptor binding, significantly reduces T3 effects on FPDc, suggesting a TRs-mediated transcriptional mechanism. RNA-seq analysis showed significant deregulation in genes involved in cardiac repolarization pathways, including several QT-interval related genes. In conclusion, long-time administration of high THs doses induces FPDc prolongation in hiPSC-CMs probably through the modulation of genes linked to QT-interval regulation. These results open the way to investigate new potential diagnostic biomarkers and specific targeted therapies for cardiac repolarization dysfunctions.

Autoantibody and hormone activation of the thyrotropin G protein-coupled receptor

Thyroid hormones are vital to growth and metabolism. Thyroid hormone synthesis is controlled by thyrotropin (TSH), which acts at the thyrotropin receptor (TSHR). Autoantibodies that activate the TSHR pathologically increase thyroid hormones in Graves' disease. How autoantibodies mimic TSH function remains unclear. We determined cryogenic-electron microscopy structures of active and inactive TSHR. In inactive TSHR, the extracellular domain lies close to the membrane bilayer. TSH selects an upright conformation of the extracellular domain due to steric clashes between a conserved hormone glycan and the membrane bilayer. An activating autoantibody selects a similar upright conformation of the extracellular domain. Conformational changes in the extracellular domain are transduced to the seven transmembrane domain via a conserved hinge domain, a tethered peptide agonist, and a phospholipid that binds within the seven transmembrane domain. Rotation of the TSHR ECD relative to the membrane bilayer is sufficient for receptor activation, revealing a shared mechanism for other glycoprotein hormone receptors that may also extend to G protein-coupled receptors with large extracellular domains.

Thyroid-stimulating hormone levels in euthyroid patients 8 years following bariatric surgery

Background Bariatric surgery (BS) was shown to promote a decline in thyroid-stimulating hormone (TSH) in euthyroid patients with severe obesity in the short-term. Aim of the present study was to assess the effect of weight loss on thyroid function in euthyroid patients in the long-term following different bariatric procedures. Methods In a retrospective cohort study including 135 patients at baseline, thyroid function was assessed at six time points up to 8 years after surgery. Patients were stratified by TSH levels at baseline and divided into two groups to compare the change in TSH at long-time. We used log-linear regression to assess the relation between thyroid hormones and TSH and linear regression analyses to identify variables that were thought to determine TSH and fT3/fT4-ratio as well as their change long-term. Results Over a mean follow-up of 8 years, TSH and fT3/fT4-ratio declined (both p < 0.001). Patients with high-normal TSH showed a greater decline in TSH than those with normal TSH compared to baseline. Thyroid hormones and TSH displayed a negative log-linear correlation at long-term follow-up. Change in TSH at long-time showed a negative correlation with TSH at baseline (B = −0.55; p < 0.001). With regard to type of surgery, there were no significant differences in TSH. Conclusion BS promotes a decline of TSH in euthyroid patients up to 8 years after intervention despite weight regain. The greatest change in TSH was seen among patients with high-normal baseline-TSH. Results of log-linear regression suggest recovery of the pituitary-thyroid axis. Type of surgery did not affect the change in TSH levels over time.

Thyroid blood profile in high-yielding dairy cows with different ovarian reactions to superovulatory treatment

The reaction of cow ovaries to superovulatory treatment significantly depends on the physiological state of the animal, primarily on its endocrine status. The available information indicates that thyroid hormones can affect the processes of ovarian folliculogenesis in cattle.Objective: To study the thyroid profile in the blood of high-yielding dairy cows in relation to the response of the ovaries to superovulatory treatment.Materials and methods. Thirty four cycles of superovulation stimulation in 16 Holstein cows were studied. After synchronization of the estrous cycle and superovulatory treatment, on the first day of insemination (Day 0), the number of follicles with a diameter of more than 5 mm was recorded in each ovary using an ultrasound scanner. Furthermore, on Day 0 and on the 7th day after insemination (Day 7), the blood was taken from the cows to analyze the content of sex steroids and thyroid hormones by ELISA. The ovarian reaction was assessed by the total number of detected follicles and was divided into 3 types: I – more than 12 follicles (strong), II – 8-12 follicles (moderate), III – less than 8 follicles (weak).Results. The content of sex steroid hormones in the blood of cows on Day 0 did not depend on the type of the ovarian response. By Day 7, the concentration of progesterone increased in most animals, but was 2.7-fold higher (P <0.01) in the case of the strong reaction (type I) than in the case of the weak reaction (type III). Conversely, the serum concentration of estradiol-17β decreased 1.1 times (P <0.05) in cows with the moderate ovarian response (type II). In animals with the type I reaction, the content of thyroxine (T4) in the blood declined 1.2 times (P <0.05) one week after insemination. During the study period, there was also a reduction in the concentration of total triiodothyronine (T3) and reverse T3 (rT3) in cows with ovarian responses of types I and II (1.1-1.3 times, P <0.01-0.05). Concurrently, on Day 0, the T3 content in the blood of individuals with the type II reaction was 1.2-fold higher (P <0.05) than in individuals with the type III reaction. Totally, a positive relationship was found between the concentration of estradiol-17β and the concentration of thyroid hormones: for T4 – in the case of the type II ovarian response (r = 0.44, P <0.05), for T3 – in the case of the type I and II responses ( r = 0.57-0.64, P <0.001-0.05), for rT3 – in the case of the type III response (r = 0.52, P <0.01).Conclusions. Thus, the content of triiodothyronine in the blood of high-yielding dairy cows on the day of insemination is associated with the ovarian response to superovulatory treatment. In addition, during one week after insemination, the state of the thyroid system and its relationship with the level of estradiol-17β in the blood differ with different reactions of the ovaries to the introduction of exogenous gonadotropic hormones.

The Association of Thyroid Hormones with Coronary Atherosclerotic Severity in Euthyroid Patients

The aim of the work was to explore the correlation between thyroid hormones and coronary atherosclerotic severity. This cross-sectional study included 340 euthyroid patients who underwent diagnostic coronary artery angiography (CAG). Gensini Score (GS) was applied to assess the severity of coronary atherosclerosis. Thyroid hormones and routine biochemical parameters were measured. The associations between thyroid hormones and coronary atherosclerosis severity were analyzed. Thyroid hormones levels or parameters were taken as both continuous variables and tertiles into analysis, and the lowest tertile was usually used as the reference (OR=1) for medium and highest tertiles. Free triiodothyronine (FT3) level was associated with GS≥22 (Median GS) in Model I adjusted for age and sex [Continuous: OR=0.46, 95% CI (0.23, 0.92), p=0.029; Tertile 3: OR=0.54, 95% CI (0.30, 0.97), p=0.038], and Model II adjusted for all known risk factors of coronary artery disease (CAD) [Continuous: OR=0.44, 95% CI (0.20, 0.95), p=0.036; Tertile 3: OR=0.49, 95% CI (0.25, 0.96), p=0.039]. Subjects with highest tertile of FT3 to free thyroxine (FT4) ratio (FT3/FT4 ratio) appeared to have the remarkably decreased risk of CAD in both Non-adjusted Model [OR=0.49, 95% CI (0.24, 0.98), p=0.044] and Model I [OR=0.45, 95% CI (0.22, 0.93), p=0.031]. Higher FT3 level within normal range was independently and negatively associated with severity of coronary atherosclerosis. Besides, FT3/FT4 ratio was remarkably correlated with the prevalence of CAD in euthyroid population.