INTRATHYROIDAL IODINE METABOLISM IN THE RAT. THE INFLUENCE OF DIET AND THE ADMINISTRATION OF THYROID-STIMULATING HORMONE.
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ABSTRACT:
SUBMITTER: BARNABY CF
PROVIDER: S-EPMC1206811 | biostudies-other | 1965 Jun
REPOSITORIES: biostudies-other
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Project description:Thyroid hormones are essential for the regulation of developmental and physiological processes. The genetic factors underlying naturally occurring variability in mammalian thyroid function are, however, only partially understood. Genetic control of thyroid function can be studied with animal models such as the inbred Wistar-Kyoto (WKY) rat strain. Previous studies established that WKY rats have elevated TSH, slightly elevated total T3, and normal total T4 levels compared with Wistar controls. The present study confirmed a persistent 24-h elevation of TSH in WKY rats compared with the Fisher 344 (F344) rat, another inbred strain. Acute T3 challenge (25 microg/100 g body weight ip) suppressed serum TSH and T4 levels in both strains. Quantitative trait locus analysis of elevated TSH in a reciprocally bred WKY x F344 F2 population identified one highly significant locus on chromosome 6 (LOD=11.7, TSH-1) and one suggestive locus on chromosome 5 (LOD=2.3, TSH-2). The confidence interval of TSH-1 contains the TSH receptor and type 2 deiodinase genes, and TSH-2 contains the type 1 deiodinase gene. The WKY alleles of each gene contain sequence alterations, but additional studies are indicated to identify the specific gene or genes responsible for altered regulation of the thyroid axis. These findings suggest that one or more genetic alterations within the TSH-1 locus significantly contribute to the altered thyroid function tests of the WKY rat.
| S-EPMC3764449 | biostudies-literature
Project description:BACKGROUND:Overt thyroid dysfunction has been associated with adverse obstetric outcomes. However, less is known regarding subclinical hypothyroidism or thyroid autoimmunity and their relationship to pregnancy complications. OBJECTIVE:The purpose of this study was to examine the association between prepregnancy anti-thyroid antibodies and subclinical hypothyroidism and preterm delivery, gestational diabetes mellitus, and preeclampsia. STUDY DESIGN:We conducted a secondary analysis of a prospective cohort of 18- to 40-year-old women with 1-2 previous pregnancy losses (n=1193) who participated in a multicenter randomized, placebo-controlled trial of low-dose aspirin. Prepregnancy levels of thyroid-stimulating hormone, free thyroxine, thyroglobulin antibody, and thyroid peroxidase antibody were measured. Relative risks and 95% confidence intervals were estimated with the use of generalized linear models with adjustment for age and body mass index. RESULTS:Among women with an ongoing pregnancy of >20 weeks estimated gestational age, there was no association between prepregnancy thyroid-stimulating hormone level (>2.5 vs ?2.5 mIU/L) and preterm delivery (adjusted relative risk, 0.77; 95% confidence interval, 0.40-1.47), gestational diabetes mellitus (adjusted relative risk, 1.28; 95% confidence interval, 0.54-3.04), or preeclampsia (adjusted relative risk, 1.20; 95% confidence interval, 0.71-2.04). Similarly, among women with thyroid antibodies, there was no increase in the likelihood of preterm delivery (relative risk, 1.26; 95% confidence interval, 0.65-2.45), gestational diabetes mellitus (relative risk, 1.33; 95% confidence interval, 0.51-3.49), or preeclampsia (relative risk, 1.02; 95% confidence interval, 0.54-1.92), compared with women without these antibodies. CONCLUSION:Among women with 1-2 previous pregnancy losses, subclinical hypothyroidism and thyroid autoimmunity were not associated with an increased risk of preterm delivery, gestational diabetes mellitus, or preeclampsia. These data support current recommendations that low-risk asymptomatic women should not be screened routinely for thyroid dysfunction or autoimmunity.
| S-EPMC5712235 | biostudies-literature
Project description:Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis may favour longevity without altering energy metabolism.
| S-EPMC4473605 | biostudies-literature
Project description:Human thyroid stimulating hormone (TSH) is a glycoprotein secreted by the anterior part of the pituitary gland. TSH plays an important physiological role in the regulation of hypothalamic-pituitary-thyroid axis by modulating the release of the thyroid hormones from the thyroid gland. It induces iodine uptake by the thyroid, promotes thyroid epithelial differentiation and growth, and protects thyroid cells from apoptosis. Impairment of TSH signal transduction pathway leads to thyroid disorders such as goitre, hypothyroidism and hyperthyroidism, which can have complex clinical manifestations. TSH signaling is largely effected through two separate pathways, the adenylate cyclase and the phospholipase C pathways. In spite of its biomedical importance, a concise signaling map of TSH pathway is not available in the public domain. Therefore, we have generated a detailed signaling map of TSH pathway by systematically cataloging the molecular reactions induced by TSH including protein-protein interactions, post-translational modifications, protein translocation events and activation/inhibition reactions. We have cataloged 40 molecular association events, 42 enzyme-substrate reactions and 16 protein translocation events in TSH signaling pathway resource. Additionally, we have documented 208 genes, which are differentially regulated by TSH. We have provided the details of TSH pathway through NetPath (http://www.netpath.org), which is a publicly available resource for human signaling pathways developed by our group. We have also depicted the map of TSH signaling using NetSlim criteria (http://www.netpath.org/netslim/) and provided pathway maps in Wikipathways (http://www.wikipathways.org/). We anticipate that the availability of TSH pathway as a community resource will enhance further biomedical investigations into the function and effects of this important hormone.
| S-EPMC3830942 | biostudies-literature
Project description:BackgroundThyroid function has been suggested to interfere with tumour biology and prognosis in different cancers. The present study was performed to investigate the impact of pre-therapeutic serum thyroid-stimulating hormone (TSH) levels on the prognosis of patients with endometrial cancer.MethodsPre-therapeutic serum TSH was investigated in 199 patients with endometrial cancer. After stratification in TSH risk groups, univariate and multivariable survival analyses were performed.ResultsElevated TSH was independently associated with poor disease-specific survival in univariate/multivariable survival analyses (P=0.01 and P=0.03, respectively).ConclusionThyroid-stimulating hormone may serve as a novel and independent prognostic parameter for disease-specific survival in patients with endometrial cancer.
| S-EPMC3708572 | biostudies-literature
Project description:BackgroundThe effects of subclinical hyperthyroidism on bone mineral density (BMD) induced by thyroid-stimulating hormone (TSH) suppression therapy in patients with differentiated thyroid cancer (DTC) remains unclear. We conducted a meta-analysis to determine the influence of TSH suppression therapy on BMD.MethodsWe performed a systematic search to identify studies which included BMD measurement of femoral neck, total hip or lumbar spine in patients on TSH suppression therapy for DTC. Main outcome measures were difference of BMD of femoral neck, total hip or lumbar spine measured by dual energy X-ray absorptiometry between patients and controls.ResultsA systematic search yielded a total of 11 published controlled cross-sectional studies (including about 571 patients and 836 controls). TSH suppression therapy was associated with the lower BMD of total hip (weighted mean difference [WMD], -0.023; 95% confidence interval [CI], -0.047 to 0.000; P=0.050) and spine (WMD, -0.041; 95% CI, -0.057 to -0.026; P<0.001) in postmenopausal women with DTC, while it was not associated with that in premenopausal women and men with DTC.ConclusionsAlthough the included studies were limited by small numbers, results suggested possible association between chronic TSH suppression therapy and the lower BMD of spine and total hip in postmenopausal women (but not in premenopausal women and men) with DTC. A large, well-designed study with long-term follow-up would provide further insight into the influence of TSH suppression therapy and loss of BMD.
| S-EPMC6416150 | biostudies-literature
Project description:Production of thyroid-stimulating hormone receptor (TSHR) antibodies represents the hallmark of Graves' disease (GD) pathogenesis. Thus, for more than two decades the TSHR gene has been at the center of studies intended to elucidate its contribution to disease pathology. The advent of genome-wide association technology allowed to establish a strong association of the TSHR gene with GD. Subsequent fine-mapping studies narrowed the disease-susceptibility region to a 40 kb sequence in intron 1, where at least five GD-associated SNPs in tight linkage disequilibrium were identified. The current challenge is to understand the functional mechanisms by which these polymorphisms modify physiological processes and trigger disease. The aim of this review is to summarize the current knowledge on the role of the TSHR gene in GD pathogenesis, which has been gained through linkage and association studies, as well as to discuss the emerging mechanisms underlying biological implications of TSHR variants in the development of GD.
| S-EPMC5376554 | biostudies-literature
Project description:BackgroundElevations or deficits in thyroid hormone levels are responsible for a wide range of neonatal and adult phenotypes. Several genome-wide, candidate gene, and meta-analysis studies have examined thyroid hormones in adults; however, to our knowledge, no genetic association studies have been performed with neonatal thyroid levels.MethodsA population of Iowa neonates, term (n = 827) and preterm (n = 815), were genotyped for 45 single-nucleotide polymorphisms (SNPs). Thyroid-stimulating hormone (TSH) values were obtained from the Iowa Neonatal Metabolic Screening Program. ANOVA was performed to identify genetic associations with TSH concentrations.ResultsThe strongest association was rs4704397 in the PDE8B gene (P = 1.3 × 10(-4)), followed by rs965513 (P = 6.4 × 10(-4)) on chromosome 9 upstream of the FOXE1 gene. Both of these SNPs met statistical significance after correction for multiple testing. Six other SNPs were marginally significant (P < 0.05).ConclusionWe demonstrated for the first time two genetic associations with neonatal TSH levels that replicate findings with adult TSH levels. These SNPs should be considered early predictors of risk for adult diseases and conditions associated with thyroid hormone levels. Furthermore, this study provides a better understanding of the thyroid profile and potential risk for thyroid disorders in newborns.
| S-EPMC3775497 | biostudies-literature
Project description:Introduction Iodine-131 (131I) is frequently used in nuclear medicine. Unbound or released 131I accumulate in the thyroid gland and may be detrimental to normal thyroid function. The aim of the present study was to identify biomarkers for 131I exposure in rat thyroid tissue and to assess the effect on thyroid function. Methods Thirty six male Sprague Dawley rats were i.v. injected with 150 µl saline solution containing 9.0, 88, 170, 260, 340, 760, 1300, or 4700 kBq (group A-H) 131I, or mock-treated with 150 µl saline solution only, and killed at 24 h after injection. Total RNA was extracted from individual thyroid tissue samples thyroids and mRNA levels were determined with the Agilent microarray platform. Results Estimated absorbed doses in treatment groups A-H was 0.0058, 0.057, 0.11, 0.17, 0.22, 0.5 Gy, 0.8 Gy, and 3 Gy. Totally, 429 transcripts were identified with a fold change fold change ≥ 1.5 and adjusted p-value ≤ 0.01. A trend with downregulation of thyroid hormone biosynthesis associated genes (e.g. thyroglobulin, thyroid peroxidase, the sodium-iodine symporter) was identified, but only statistically significant after 0.0058 and 0.22 Gy. Three transcripts coding for isoform 1 of the DBP protein showed a pattern with monotonous decrease in downregulation with absorbed dose between 0.0058-0.22 Gy. Changes in Dbp expression were not statistically significant between 0.5-3 Gy. However, a trend with downregulation at 0.5 and 0.8 Gy and upregulation and 3 Gy was identified. Previously, 131I (0.85-17 Gy) and 211At (0.023-32 Gy) exposure resulted in upregulation of Dbp in mice thyroid tissue 24 h after administrations. Additionally, a monotonous decrease in Dbp downregulation has been identified of in mouse kidney tissue at 8 and 12 months after 177Lu-octreotate administrations. Conclusion Conclusively, the Dbp gene is a promising candidate biomarker gene for exposure to 131I and possibly other internal radiation emitters. Further studies should be performed to establish how Dbp expression vary with dose-rate, absorbed dose, time after administration, different radiation qualities, and the function of Dbp.
2016-06-30 | GSE66623 | GEO
Project description:BackgroundThe relationship between normal thyroid-stimulating hormone (TSH) levels and thyroid disease in adults remains controversial. This study aimed to investigate the correlation between serum TSH levels, particularly those falling within the normal range, and thyroid diseases in Chinese adults, including thyroid nodules (TN), goiter (GR), and thyroid antibody positivity.Materials and methodsThis research was a cross-sectional study conducted in an adult population in Tianjin, China. Thyroid volume (Tvol) and TN were assessed using thyroid ultrasonography. Fasting venous blood and spot urine samples were collected to evaluate thyroid function and iodine status.ResultsA total of 2460 subjects participated in the survey. The prevalence of thyroid dysfunction was 9.76%, and abnormal TSH levels were found to potentially increase the risk of GR and thyroid antibody positivity in adults. A total of 2220 subjects with TSH within the normal reference range were included in the further study. In these patients, Tvol decreased as TSH levels increased, in both men and women (P < 0.0001). Low TSH levels (0.27-1.41 IU/mL) were identified as a risk factor for TN (odds ratio [OR], 1.46; 95% CI: 1.14-1.87) and GR (OR 5.90, 95% CI 2.27-15.3). Upon stratification by sex and age, the risk of TN was found to be higher in women and elderly individuals (≥60 years old), while the risk of GR was found to be higher in men and younger individuals (<60 years old). High TSH levels (2.55-4.2 IU/mL) were identified as a risk factor for thyroid antibody positivity (OR, 1.53; 95% CI: 1.11-2.10). Men and younger individuals with high TSH levels exhibited a higher risk of thyroid antibody positivity.ConclusionIn adults with normal TSH levels, low TSH levels were associated with an increased risk of TN and GR, whereas high TSH levels were associated with thyroid antibody positivity. The research also suggests that adults whose TSH levels at upper or lower limits of the normal range should be reviewed regularly.
| S-EPMC10577406 | biostudies-literature