scholarly journals A thyroid hormone network exists in synovial fibroblasts of rheumatoid arthritis and osteoarthritis patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna-Sophia Pörings ◽  
Torsten Lowin ◽  
Bianca Dufner ◽  
Joachim Grifka ◽  
Rainer H. Straub

Abstract While patients with rheumatoid arthritis (RA) sometimes demonstrate thyroidal illness, the role of thyroid hormones in inflamed synovial tissue is unknown. This is relevant because thyroid hormones stimulate immunity, and local cells can regulate thyroid hormone levels by deiodinases (DIO). The study followed the hypothesis that elements of a thyroid hormone network exist in synovial tissue. In 12 patients with RA and 32 with osteoarthritis (OA), we used serum, synovial fluid, synovial tissue, and synovial fibroblasts (SF) in order to characterize the local thyroid hormone network using ELISAs, immunohistochemistry, imaging methods, tissue superfusion studies, cell-based ELISAs, flow cytometry, and whole genome expression profiling. Serum/synovial fluid thyroid hormone levels were similar in RA and OA (inclusion criteria: no thyroidal illness). The degradation product termed reverse triiodothyronine (reverse T3) was much lower in serum compared to synovial fluid indicating biodegradation of thyroid hormones in the synovial environment. Superfusion experiments with synovial tissue also demonstrated biodegradation, particularly in RA. Cellular membrane transporters of thyroid hormones, DIOs, and thyroid hormone receptors were present in tissue and SF. Density of cells positive for degrading DIOs were higher in RA than OA. TNF increased protein expression of degrading DIOs in RASF and OASF. Gene expression studies of RASF revealed insignificant gene regulation by bioactive T3. RA and OA synovial tissue/SF show a local thyroid hormone network. Thyroid hormones undergo strong biodegradation in synovium. While bioactive T3 does not influence SF gene expression, SF seem to have a relay function for thyroid hormones.

2003 ◽  
Vol 81 (9) ◽  
pp. 890-893 ◽  
Author(s):  
Jörg W Wegener ◽  
Matthias Lee ◽  
Franz Hofmann

Thyroid hormones are known to influence various processes of cell differentiation. Recently, it was reported that hypothyroidism reduces the sensitivity to Ca2+-channel antagonists in the rat uterus. We examined the sensitivity to dihydropyridines of the uterus from mice that had reduced thyroid hormone levels. Isradipine relaxed with the same potency precontracted uterine muscle strips from control and hypothyroid mice, independently from a pseudo-pregnant state. These results demonstrate that hypothyroidism does not change dihydropyridine sensitivity (i.e., the pattern of Ca2+-channel expression) in the murine uterus.Key words: uterus, smooth muscle, Ca2+ channel, isradipine.


2020 ◽  
Vol 244 (1) ◽  
pp. 83-94 ◽  
Author(s):  
Ángela Sánchez ◽  
Constanza Contreras-Jurado ◽  
Diego Rodríguez ◽  
Javier Regadera ◽  
Susana Alemany ◽  
...  

Hypothyroidism is often associated with anemia and immunological disorders. Similar defects are found in patients and in mice with a mutated dominant-negative thyroid hormone receptor α (TRα) and in knockout mice devoid of this receptor, suggesting that this isoform is responsible for the effects of the thyroid hormones in hematopoiesis. However, the hematological phenotype of mice lacking also TRβ has not yet been examined. We show here that TRα1/TRβ-knockout female mice, lacking all known thyroid hormone receptors with capacity to bind thyroid hormones, do not have overt anemia and in contrast with hypothyroid mice do not present reduced Gata1 or Hif1 gene expression. Similar to that found in hypothyroidism or TRα deficiency during the juvenile period, the B-cell population is reduced in the spleen and bone marrow of ageing TRα1/TRβ-knockout mice, suggesting that TRβ does not play a major role in B-cell development. However, splenic hypotrophy is more marked in hypothyroid mice than in TRα1/TRβ-knockout mice and the splenic population of T-lymphocytes is not significantly impaired in these mice in contrast with the reduction found in hypothyroidism. Our results show that the overall hematopoietic phenotype of the TRα1/TRβ-knockout mice is milder than that found in the absence of hormone. Although other mechanism/s cannot be ruled out, our results suggest that the unoccupied TRs could have a negative effect on hematopoiesis, likely secondary to repression of hematopoietic gene expression.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Shariq Rashid Masoodi ◽  
Rameesa Batul ◽  
Khurram Maqbool ◽  
Amir Zahoor ◽  
Mona Sood ◽  
...  

Abstract BACKGROUND: The association between thyroid dysfunction and postoperative mortality is contentious. Thyroid function is frequently depressed during and after cardiopulmonary bypass surgical procedures, and this may adversely affect myocardial performance and postop outcome.OBJECTIVES: To study i) the changes and clinical significance of serum thyroid hormones during cardiopulmonary bypass (CPB), and ii) the association between biochemically assessed peri-op thyroid function and 30-day mortality after CBPSTUDY DESIGN: Prospective Cohort StudySUBJECTS: 279 patients undergoing various cardiac surgeries under cardiopulmonary bypass.METHODS: All consenting patients undergoing open heart surgery in last five years at a tertiary care centre in North-India were studied. The thyroid hormone levels (Total T3, T4 and TSH) were measured before admission, and postoperatively on Day 1 & 7, and 3 months following surgery. The patients’ gender, age, weight, body mass index, heart disease details, previous cardiac surgeries, and cardiac surgery-related data such as pump time, aortic clamping time, hypothermia duration, postoperative hemodynamic status and postoperative use of inotropic drugs were recorded and analysed. Patients were classified as having biochemically overt or subclinical hyperthyroidism or hypothyroidism, normal thyroid function, or non-classifiable state based on preoperative thyroid-stimulating hormone and total T4 values. Outcome data were collected from hospital records. Biochemical thyroid dysfunction was not systematically treated. Outcomes measured were length of ICU stay, postoperative complications and 30-day mortality.RESULTS: There was significant changes in thyroid function in patients undergoing cardiopulmonary bypass surgery (Fig 1). All patients showed a decrease in T3, T4 and TSH after surgery. Post-op complications were observed in 137 patients (49%) most common being atrial fibrillation (34%) followed by acute kidney injury (23%), infections (18%), dyselectrolytemia (7%), bleeding (1.4%) and ARDS (1.4%). Of 263 patients followed, eventually 26 patients expired with a mortality rate of 8.89% (95% CI, 0.4 - 19.4). Perioperatively, there was a significant correlation between 30-day with type of surgery (r, 0.26), aortic clamp time (r, 0.45), CBP time (r, 0.48), number of inotropes used (r, 0.57), hours of mechanical ventilation (r, 0.4), ICU stay (r, 0.13) and post-op complications (r, 0.24), as well as with the reduction in the thyroid hormone levels; 17 (7%), 3 (20%) and 6 (46%) patients of those with pre-op TSH level of <6.5, >6.5 and >10.5 mIU/L expired (p <0.001).CONCLUSION: Pre-op thyroid dysfunction is associated with increased mortality in patients undergoing cardiac surgery with CBP. Excess mortality with elevated serum TSH levels suggests the importance of timely detection and intervention in individuals with thyroid dysfunction undergoing cardiac surgery.Table of Contents oTable 1. Characteristics of patients who expired versus those who survived cardiac surgery with cardiopulmonary bypass (CPB) oFig 1. Changes in serum thyroid hormones during CPB surgery oTable 1. Characteristics of patients who expired versus those who survived cardiac surgery with cardiopulmonary bypass (CPB) oFigures in parenthesis indicate ±Standard Deviation, unless indicated otherwise oFig 1. Changes in serum thyroid hormones during CPB surgery


2005 ◽  
Vol 288 (5) ◽  
pp. R1264-R1272 ◽  
Author(s):  
Samantha J. Richardson ◽  
Julie A. Monk ◽  
Caroline A. Shepherdley ◽  
Lars O. E. Ebbesson ◽  
Frank Sin ◽  
...  

Thyroid hormones are essential for vertebrate development. There is a characteristic rise in thyroid hormone levels in blood during critical periods of thyroid hormone-regulated development. Thyroid hormones are lipophilic compounds, which readily partition from an aqueous environment into a lipid environment. Thyroid hormone distributor proteins are required to ensure adequate distribution of thyroid hormones, throughout the aqueous environment of the blood, and to counteract the avid partitioning of thyroid hormones into the lipid environment of cell membranes. In human blood, these proteins are albumin, transthyretin and thyroxine-binding globulin. We analyzed the developmental profile of thyroid hormone distributor proteins in serum from a representative of each order of marsupials ( M. eugenii; S.crassicaudata), a reptile ( C. porosus), in two species of salmonoid fishes ( S. salar; O. tshawytsch), and throughout a calendar year for sea bream ( S. aurata). We demonstrated that during development, these animals have a thyroid hormone distributor protein present in their blood which is not present in the adult blood. At least in mammals, this additional protein has higher affinity for thyroid hormones than the thyroid hormone distributor proteins in the blood of the adult. In fish, reptile and polyprotodont marsupial, this protein was transthyretin. In a diprotodont marsupial, it was thyroxine-binding globulin. We propose an hypothesis that an augmented thyroid hormone distributor protein network contributes to the rise in total thyroid hormone levels in the blood during development.


2020 ◽  
Vol 36 (5) ◽  
Author(s):  
Sabeen Nasir ◽  
Sara Ziaullah ◽  
Sadaf Alam ◽  
Muhammad Mumtaz Khan

Objectives: To study the morphological spectrum of endometrial changes with the thyroid hormone levels in infertile women. Methods: This cross sectional study was conducted at Department of Pathology, Peshawar Medical College, Health Care Centre and Madina Medical Laboratory, Peshawar from April 2013 to August 2013. Total 160 cases of infertile women were included in the study. Biopsies were taken on 22-23rd day of menstrual cycle. Statistical Analysis was performed using SPSS version 19 statistical program. Difference between endometrial findings of patients with normal thyroid profile and abnormal one were analyzed for statistical significance using Chi square test. Probability values p ≤ 0.05 were considered statistically significant. Results: In our study, majority infertile women were euthyroid (80%), followed by hyperthyroid (18%) and only two% to be hypothyroid. The correlation of endometrial morphology with thyroid hormones levels turned out to be insignificant. While correlating histological details of endometrial biopsy with thyroid hormone status, we found significant association of leukocytic infiltrate with thyroid hormone levels. Conclusion: This study shows that thyroid hormones may have role in early leukocytic infiltration into stroma, and a possibility of immune modulation by altered thyroid hormones in causing infertility. doi: https://doi.org/10.12669/pjms.36.5.1791 How to cite this:Nasir S, Ziaullah S, Alam S, Khan MM. Morphological spectrum of endometrium with thyroid hormone profile in infertile female population of Khyber Pakhtunkhwa province of Pakistan. Pak J Med Sci. 2020;36(5):---------. doi: https://doi.org/10.12669/pjms.36.5.1791 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


1974 ◽  
Vol 12 (8) ◽  
pp. 31-32

Thyrotrophin-releasing hormone (TRH - Roche) is a synthetic tripeptide, L-pyroglutamyl-L-histidyl-L-proline-amide, which is identical with the porcine, ovine and human hypothalamic hormone that promotes the secretion of thyrotrophin. Secreted in the hypothalamus, it passes down the capillaries of the pituitary stalk to the anterior pituitary and there causes release of thyrotrophin. Thyroid hormones (triiodo-thyronine (T3) and thyroxine (T4)) interfere with the thyrotrophin (TSH)-releasing action of TRH, so that excess thyroid hormones block TSH release in response to TRH; conversely when thyroid hormone levels are low, increased secretion of TSH occurs. The hypothalamic secretion of TRH is probably directly influenced by the concentration of thyroid hormones in the blood reaching it. In addition TRH promotes the secretion of prolactin from the pituitary. TRH-Roche is marketed in Britain for use in hospitals in diagnostic tests of thyroid and of pituitary-hypothalamic function.


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