scholarly journals Analysis of Hypothalamic TRH Neurons in Regulating Thyroid Hormone Levels

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A849-A849
Author(s):  
Ricardo H Costa e Sousa ◽  
Rodrigo Rorato ◽  
Anthony Neil Hollenberg ◽  
Kristen R Vella
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Designer Drugs ◽  
Mrna Levels ◽  
Hormone Levels ◽  
Males And Females ◽  
Thyroid Hormone Levels ◽  
Hpt Axis ◽  
Tsh Levels

Abstract Thyroid hormone (TH) is a major regulator of development and metabolism. An important mechanism controlling TH production is the negative feedback at the hypothalamic and pituitary level and it has been suggested that thyroid hormone receptor β (TRβ) is the main mediator of TH actions in the hypothalamic paraventricular nucleus (PVN). Nevertheless, the direct actions of TH and TRβ in the negative regulation of TRH have yet to be demonstrated in vivo. Here we used two approaches to investigate the TRH neuron. First, we used a chemogenetic tool to directly investigate the role of TRH neurons on the regulation of thyroid hormone levels. Mice expressing Cre-recombinase in TRH neurons received bilateral injections of the activating designer receptors exclusively activated by designer drugs (DREADD) directly into the PVN. Activation of TRH neurons produced a rapid and sustained increase in circulating TSH levels in both males and females. TSH levels increased approximately 10-fold from baseline within 15 minutes of injection of CNO, returning to baseline within 2.5 hours. TH levels were increased approximately 2-fold in males and females. Therefore, using a chemogenetic approach, we were able to directly evaluated the role of PVN TRH neurons on the control of thyroid activity, for the first time. Next, we generated mice deficient in TRβ specifically in neurons expressing melanocortin 4 receptor (MC4R), which overlaps with TRH expression in the PVN. Knockout mice (KO) developed normally and showed no change in TH and TSH levels. TRH mRNA levels in the PVN of KO mice were similar to control mice. To investigate if the deletion of TRβ in the PVN changes the sensitivity of the HPT axis to T3, mice were rendered hypothyroid and given increasing doses of T3 for 2 weeks. Results show no difference in TRH mRNA or serum TSH between controls and KO. Surprisingly, despite the presence of detectable genomic recombination on the TRβ gene in the PVN, there was no difference in TRβ mRNA expression between control and KO mice, suggesting that either MC4R-positive neurons do not express TRβ or they represent a very small population of TRβ-positive cells in the PVN. Present data show that TRH neuron activation rapidly stimulates TSH release and increases TH levels, demonstrating a major role of these neurons in the regulation of the hypothalamic-pituitary-thyroid (HPT) axis. Nevertheless, deletion of TRβ from MC4R neurons had no major effect on either TRH or TH levels in in mice. Additionally, TRβ in MC4R-positive TRH neurons in the PVN is not necessary for TH-induced suppression of TRH mRNA. Although further studies are necessary, these data suggest that there are distinct populations of hypophysiotropic TRH neurons in the PVN, some of which are not regulated by thyroid hormone and TRβ.

scholarly journals TDCPP exposure affects the concentrations of thyroid hormones in zebrafish

2017 ◽  
Author(s):  
Jingxin Song
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Survival Rates ◽  
Mrna Levels ◽  
Expression Levels ◽  
Hormone Levels ◽  
Zebrafish Larvae ◽  
Thyroid Hormone Levels ◽  
Hpt Axis ◽  
Mrna Expression Levels

AbstractPrevious studies show that TDCPP may interrupt the thyroid endocrine system, however, the potential mechanisms involved in these processes were largely unknown. In this study, zebrafish embryos/larvae were exposed to TDCPP until 120 hpf, by which time most of the organs of the larvae have completed development. In this study, the effects of TDCPP on HPT axis were examined and the thyroid hormone levels were measured after TDCPP treatment. Zebrafish (Danio rerio) embryos were treated with a series concentration of TDCPP (10, 20, 40, 80, 160 and 320 μg/L) from 1 day post-fertilization (dpf) to 5 dpf. Exposure concentrations of TDCPP were determined based on the survival rates in each group. Total mRNA were isolated, first-strand cDNA were synthesis and qPCR were performed to detect the mRNA expression levels in hypothalamic-pituitary-thyroid (HPT) axis. The mRNA expression levels of genes involved in thyroid hormone homeostasis were increased in the TDCPP-treated larvae. The mRNA levels of genes involved in thyroid hormone synthesis were also increased in the embryos treated with TDCPP. Furthermore, exposure to TDCPP led to a dose-dependent effect on zebrafish development, including diminished hatching and survival rates, increased malformation. TDCPP treatment significantly reduced the T4 concentration in the 5 dpf zebrafish larvae, but increased the concentration of T3, suggesting the function of thyroid endocrine were interrupted in the TDCPP-exposed zebrafish. Taken together, these data indicated that TDCPP affected the thyroid hormone levels in the zebrafish larvae and could increased the mRNA expression levels of genes related to HPT axis, which further impaired the endocrine homeostasis and thyroid system.

scholarly journals Thyroid Hormone Resistance Syndrome Presenting as Exercise Induced Asthma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A707-A708
Author(s):  
Joshua D Umscheid ◽  
Naim Mitre ◽  
Fadi Jamil Odeh Al Muhaisen
Keyword(s):  
Genetic Testing ◽  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Receptor Gene ◽  
Target Tissue ◽  
Hormone Resistance ◽  
Color Flow ◽  
Thyroid Hormone Resistance ◽  
Hormone Levels ◽  
Thyroid Hormone Levels

Abstract Background: Pathogenic variants in the thyroid hormone receptor (THRB) gene are associated with thyroid hormone resistance. Over 85% of the genetic mutations are in the beta TR gene. The disorder is characterized mainly by elevated thyroid hormone levels, unsuppressed levels of TSH, and goiter. Clinical case: An 11-year-old male initially seen at the PCP office for tachycardia and chest discomfort, especially during school exercise. He reported shortness of breath. His symptoms will resolve at rest. He was diagnosed initially with asthma and was put on Singular, Pulmicort, and albuterol as needed. His symptoms did not improve with this treatment, and he reported symptoms worsened with albuterol. He had a normal Echocardiogram and chest X-ray. A mild goiter was noted on his physical exam. Thyroid ultrasound showed an enlarged thyroid gland. An ovoid echogenic focus in the inferior thyroid lobe measuring 4 X 7 X 8mm was identified. The nodule was wider than tall, with a solid appearance with no internal color flow. Evaluation in our clinic showed normal TSH at 1.624mcIU/mL (0.35-5.5). FT4 was high at 1.54ng/dL (0.82-1.40), and FT3 elevated at 6.3pg/mL (3.3-4.8). Thyroid antibodies and thyroid-stimulating immunoglobulin (TSI) were normal. A 24 hour I-123 thyroid uptake was approximately 55% (10-30%) with no focal increased or decreased uptake. Given his elevated thyroid hormone levels with unsuppressed TSH in the context of goiter and tachycardia, genetic testing for the Thyroid receptor gene was done. He was found to be heterozygous for a pathogenic variant in THRB, c.1286G>A (p.Arg429Gln). This genotype is consistent with a diagnosis of autosomal dominant Thyroid hormone resistance. The patient was started on Atenolol, given his elevated heart rate, and he reported improvement in his symptoms during exercise. Conclusion: Thyroid hormone resistance was first described as a clinical entity in 1967. The phenotype can vary among individuals. It is characterized by a reduced responsiveness of target tissue to thyroid hormone and binding affinity. The disease can present with goiter, behavioral issues, abnormal growth, and tachycardia. Affected individuals may have attention deficit-hyperactivity disorders (ADHD) and language difficulties. Thyroid hormone resistance can be misdiagnosed, as in our patient. He was diagnosed with asthma and was put on unnecessary medications that worsened his symptoms. Thyroid hormone resistance can also be misdiagnosed with Graves’ disease, given the elevated thyroid hormone. It is essential to highlight the importance of genetic testing in these cases, as an accurate diagnosis will prevent unnecessary treatments with potentially serious side effects.

scholarly journals Manipulating plasma thyroid hormone levels at hatching alters development of endothermy and ventilation in Pekin duck (Anas platyrhynchos domestica)

2020 ◽  
Vol 223 (22) ◽  
pp. jeb237701
Author(s):  
Tushar S. Sirsat ◽  
Edward M. Dzialowski
Keyword(s):  
Thyroid Hormone ◽  
Tidal Volume ◽  
Developmental Trajectory ◽  
Pekin Duck ◽  
Thyroid Peroxidase ◽  
Hormone Levels ◽  
Ventilation Frequency ◽  
Thyroid Hormone Levels ◽  
And Control

ABSTRACTAt hatching in precocial birds, there are rapid physiological and metabolic phenotypic changes associated with attaining endothermy. During the transition to ex ovo life, thyroid hormone levels naturally increase, peaking at hatching, and then decline. To better understand the role of the natural increase in thyroid hormone at hatching in regulating the developmental trajectory of the Pekin duck's endothermic phenotype, we examined development of O2 consumption (V̇O2) and ventilation (frequency, tidal volume and minute ventilation) while inhibiting the developmental increase in thyroid hormones that occurs at hatching via administration of the thyroid-peroxidase inhibitor methimazole (MMI) or accelerating the developmental increase via triiodothyronine (T3) supplementation. Animals were dosed only on day 24 of a 28-day incubation period and studied on incubation day 25, during external pipping (EP) and 1 day post-hatching (dph). On day 25, there was an increase in V̇O2 in the hyperthyroid treatment compared with the other two treatments. During the EP stage, there was a significant effect of thyroid status on V̇O2, with hyperthyroid V̇O2 being highest and hypothyroid V̇O2 the lowest. By 1 dph, the supplemented T3 and control animals had similar V̇O2 responses to cooling with comparable thermal neutral zones followed by increased V̇O2. Hypothyroid 1 dph hatchlings had a lower resting V̇O2 that did not increase to the same extent as the supplemented T3 and control animals during cooling. During EP, inhibiting the rise in T3 resulted in embryos with lower ventilation frequency and tidal volume than control and supplemented T3 embryos. At 1 dph, ventilation frequency of all animals increased during cooling, but tidal volume only increased in supplemented T3 and control hatchlings. Our data support the role of the late incubation increase in T3 in regulating the systemic development of endothermic metabolic capacity and associated control of ventilation occurring at hatching of the Pekin duck.

STUDIES ON THE ORIGIN OF ALTERED THYROID HORMONE LEVELS IN THE BLOOD OF RATS DURING COLD EXPOSURE

1979 ◽  
Vol 91 (3) ◽  
pp. 484-492 ◽  
Author(s):  
C. van Hardeveld ◽  
M. J. Zuidwijk ◽  
A. A. H. Kassenaar
Keyword(s):  
Thyroid Hormone ◽  
Cold Exposure ◽  
Plasma Levels ◽  
Dose Regimen ◽  
Sympathetic Activity ◽  
Chemical Sympathectomy ◽  
Hormone Levels ◽  
Thyroid Hormone Levels ◽  
Altered Thyroid

ABSTRACT The effect of sympathetic activity on T4 and T3 levels in cold-exposed rats was investigated. Administration of the highest dose of propranolol (2 mg/100 g b.w.) twice daily during 4 days decreased T4 and T3 concentrations in plasma of rats living at 23°C (T4 from 46.4 ± 2.6 to 25.8 ± 5.3 nmol/l and T3 from 1.08. ± 0.6 to 0.82 ± 0.12 nmol/l). No significant effect on T4 and T3 levels (49.0 ± 11.6 and 1.48 ± 0.16 n/mol, respectively) after the administration of the same dose regimen of propranolol was observed in rats exposed to cold for 4 weeks. T4 and T3 levels in rats exposed to cold for 4 weeks were not significantly altered 1 week after sympathectomy, while remaining in the cold. However, chemical sympathectomy before cold exposure delayed the cold induced T3 elevation occurring during the first week of cold exposure (controls: from 1.16 ± 0.19 to 1.44 ± 0.29 nmol/l; sympathectomized rats: from 1.07 ± 0.12 to 1.17 ± 0.22 nmol/l). After 2 weeks of cold exposure the T3 levels of controls and sympathectomized rats were not significantly different (controls: 1.45 ± 0.12 nmol/l, sympathectomized rats: 1.38 ± 0.15 nmol/l). No effect of sympathectomy was observed on T4 levels. These experiments show that the role of sympathetic activity in increasing T3 is not clear during cold exposure. They provide some evidence that sympathetic activity may play a role in the initiation of the process leading to increased T3 plasma levels during cold exposure.

scholarly journals Lacking thyroid hormone receptor β gene does not influence alterations in peripheral thyroid hormone metabolism during acute illness

2008 ◽  
Vol 197 (1) ◽  
pp. 151-158 ◽  
Author(s):  
J Kwakkel ◽  
O Chassande ◽  
H C van Beeren ◽  
W M Wiersinga ◽  
A Boelen
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Males And Females ◽  
Induced Changes ◽  
Thyroid Hormone Receptor Β

The downregulation of liver deiodinase type 1 (D1) is supposed to be one of the mechanisms behind the decrease in serum tri-iodothyronine (T3) observed during non-thyroidal illness (NTI). Liver D1 mRNA expression is positively regulated by T3, mainly via the thyroid hormone receptor (TR)β1. One might thus expect that lacking the TRβ gene would result in diminished downregulation of liver D1 expression and a smaller decrease in serum T3 during illness. In this study, we used TRβ−/− mice to evaluate the role of TRβ in lipopolysaccharide (LPS, a bacterial endotoxin)-induced changes in thyroid hormone metabolism. Our results show that the LPS-induced serum T3 and thyroxine and liver D1 decrease takes place despite the absence of TRβ. Furthermore, we observed basal differences in liver D1 mRNA and activity between TRβ−/− and wild-type mice and TRβ−/− males and females, which did not result in differences in serum T3. Serum T3 decreased rapidly after LPS administration, followed by decreased liver D1, indicating that the contribution of liver D1 during NTI may be limited with respect to decreased serum T3 levels. Muscle D2 mRNA did not compensate for the low basal liver D1 observed in TRβ−/− mice and increased in response to LPS in TRβ−/− and WT mice. Other (TRβ independent) mechanisms like decreased thyroidal secretion and decreased binding to thyroid hormone-binding proteins probably play a role in the early decrease in serum T3 observed in this study.

scholarly journals Iodothyronine deiodinases and the control of plasma and tissue thyroid hormone levels in hyperthyroid tilapia (Oreochromis niloticus)

2005 ◽  
Vol 184 (3) ◽  
pp. 467-479 ◽  
Author(s):  
S Van der Geyten ◽  
N Byamungu ◽  
G E Reyns ◽  
E R Kühn ◽  
V M Darras
Keyword(s):  
Thyroid Hormone ◽  
Oreochromis Niloticus ◽  
Degradation Mechanism ◽  
Current Data ◽  
Type I ◽  
Iodothyronine Deiodinase ◽  
Hormone Levels ◽  
Thyroid Hormone Levels

Thyroid status is one of the most potent regulators of peripheral thyroid hormone metabolism in vertebrates. Despite this, the few papers that have been published concerning the role of thyroid hormones in the regulation of thyroid function in fish often offer conflicting data. We therefore set out to investigate the effects of tetraiodothyronine (thyroxine) (T4) or tri-iodothyronine (T3) supplementation (48 p.p.m.) via the food on plasma and tissue thyroid hormone levels as well as iodothyronine deiodinase (D) activities in the Nile tilapia (Oreochromis niloticus). T4 supplementation did not induce a hyperthyroid state and subsequently had no effects on the thyroid hormone parameters measured, with the liver as the sole notable exception. In T4-fed tilapias, the hepatic T4 levels increased substantially, and this was accompanied by an increase in in vitro type I deiodinase (D1) activity. Although the lack of effect of T4 supplementation could be partially explained by an inefficient uptake of T4 from the gut, our current data suggest that also the increased conversion of T4 into reverse (r)T3 by the D1 present in the liver plays an important role in this respect. In addition, T3 supplementation increased plasma T3 and decreased plasma T4 concentrations. T3 levels were also increased in the liver, brain, kidney, gill and white muscle, but without affecting local T4 concentrations. However, this increase in T3 availability remained without effect on D1 activity in liver and kidney. This observation, together with the 6-n-propylthiouracyl (PTU) insensitivity of the D1 enzyme in fish, sets the D1 in teleost fish clearly apart from its mammalian and avian counterparts. The changes in hepatic deiodinases confirm the role of the liver as an important T3-regulating tissue. However, the very short plasma half-life of exogenously administered T3 implies the existence of an efficient T3 clearing/degradation mechanism other than deiodination.

Altered thyroid hormone levels in bacterial sepsis: The role of nutritional adequacy

Metabolism ◽  
1980 ◽  
Vol 29 (10) ◽  
pp. 936-942 ◽  
Author(s):  
David A. Richmand ◽  
Mark E. Molitch ◽  
Thomas F. O'Donnell
Keyword(s):  
Thyroid Hormone ◽  
Bacterial Sepsis ◽  
Nutritional Adequacy ◽  
Hormone Levels ◽  
Thyroid Hormone Levels ◽  
Altered Thyroid

scholarly journals Thyroid hormone receptor β2 is strongly up-regulated at all levels of the hypothalamo–pituitary–thyroidal axis during late embryogenesis in chicken

2007 ◽  
Vol 196 (3) ◽  
pp. 519-528 ◽  
Author(s):  
Sylvia V H Grommen ◽  
Lutgarde Arckens ◽  
Tim Theuwissen ◽  
Veerle M Darras ◽  
Bert De Groef
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Thyroid Hormone Receptor ◽  
Expression Patterns ◽  
Perinatal Period ◽  
Mrna Levels ◽  
Late Embryogenesis ◽  
Mrna Content ◽  
Hpt Axis

In this study, we tried to elucidate the changes in thyroid hormone (TH) receptor β2 (TRβ2) expression at the different levels of the hypothalamo–pituitary–thyroidal (HPT) axis during the last week of chicken embryonic development and hatching, a period characterized by an augmented activity of the HPT axis. We quantified TRβ2 mRNA in retina, pineal gland, and the major control levels of the HPT axis – brain, pituitary, and thyroid gland – at day 18 of incubation, and found the most abundant mRNA content in retina and pituitary. Thyroidal TRβ2 mRNA content increased dramatically between embryonic day 14 and 1 day post-hatch. In pituitary and hypothalamus, TRβ2 mRNA expression rose gradually, in parallel with increases in plasma thyroxine concentrations. Using in situ hybridization, we have demonstrated the presence of TRβ2 mRNA throughout the diencephalon and confirmed the elevation in TRβ2 mRNA expression in the hypophyseal thyrotropes. In vitro incubation with THs caused a down-regulation of TRβ2 mRNA levels in embryonic but not in post-hatch pituitaries. The observed expression patterns in pituitary and diencephalon may point to substantial changes in TRβ2-mediated TH feedback active during the perinatal period. The strong rise in thyroidal TRβ2 mRNA content could be indicative of an augmented modulation of thyroid development and/or function by THs toward and after hatching. Finally, THs proved to exert an age-dependent effect on pituitary TRβ2 mRNA expression.

scholarly journals Thyroid testing paradigm switch from thyrotropin to thyroid hormones—Future directions and opportunities in clinical medicine and research

Endocrine ◽  
2021 ◽  
Vol 74 (2) ◽  
pp. 285-289
Author(s):  
Stephen P. Fitzgerald ◽  
Nigel G. Bean ◽  
James V. Hennessey ◽  
Henrik Falhammar
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Dysfunction ◽  
Clinical Medicine ◽  
Older Individuals ◽  
Free Triiodothyronine ◽  
Thyroid State ◽  
Peripheral Tissues ◽  
Hormone Levels ◽  
Thyroid Hormone Levels ◽  
Tsh Levels

Abstract Purpose Recently published papers have demonstrated that particularly in untreated individuals, clinical parameters more often associate with thyroid hormone, particularly free thyroxine (FT4), levels than with thyrotropin (TSH) levels. Clinical and research assessments of the thyroid state of peripheral tissues would therefore be more precise if they were based on FT4 levels rather than on TSH levels. In this paper we describe implications of, and opportunities provided by, this discovery. Conclusions The FT4 level may be the best single test of thyroid function. The addition of free triiodothyronine (FT3) and TSH levels would further enhance test sensitivity and distinguish primary from secondary thyroid dysfunction respectively. There are opportunities to reconsider testing algorithms. Additional potential thyroidology research subjects include the peripheral differences between circulating FT4 and FT3 action, and outcomes in patients on thyroid replacement therapy in terms of thyroid hormone levels. Previously performed negative studies of therapy for subclinical thyroid dysfunction could be repeated using thyroid hormone levels rather than TSH levels for subject selection and the monitoring of treatment. Studies of outcomes in older individuals with treatment of high normal FT4 levels, and pregnant women with borderline high or low FT4 levels would appear to be the most likely to show positive results. There are fresh indications to critically re-analyse the physiological rationale for the current preference for TSH levels in the assessment of the thyroid state of the peripheral tissues. There may be opportunities to apply these research principles to analogous parameters in other endocrine systems.

scholarly journals Association of High Vitamin D Status with Low Circulating Thyroid-Stimulating Hormone Independent of Thyroid Hormone Levels in Middle-Aged and Elderly Males

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Qingqing Zhang ◽  
Zhixiao Wang ◽  
Min Sun ◽  
Mengdie Cao ◽  
Zhenxin Zhu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Thyroid Hormone ◽  
Smoking Status ◽  
Thyroid Stimulating Hormone ◽  
Vitamin D Status ◽  
Middle Aged ◽  
Hormone Levels ◽  
Elderly Males ◽  
Thyroid Hormone Levels ◽  
Tsh Levels

Background. A recent study has reported that high circulating 25-hydroxyvitamin D [25(OH)D] is associated with low circulating thyroid-stimulating hormone (TSH) levels, but only in younger individuals. The goal of the present study was to explore the relationship between vitamin D status and circulating TSH levels with thyroid autoimmunity and thyroid hormone levels taken into consideration in a population-based health survey of middle-aged and elderly individuals.Methods. A total of 1,424 Chinese adults, aged 41–78 years, were enrolled in this cross-sectional study. Serum levels of 25(OH)D, TSH, thyroid hormones, and thyroid autoantibodies were measured.Results. The prevalence of vitamin D insufficiency was 94.29% in males and 97.22% in females, and the prevalence of vitamin D deficiency was 55.61% in males and 69.64% in females. Vitamin D status was not associated with positive thyroid autoantibodies after controlling for age, gender, body mass index, and smoking status. Higher 25(OH)D levels were associated with lower TSH levels after controlling for age, FT4 and FT3 levels, thyroid volume, the presence of thyroid nodule(s), and smoking status in males.Conclusion. High vitamin D status in middle-aged and elderly males was associated with low circulating TSH levels independent of thyroid hormone levels.

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