Thyrotropin (TSH) regulates triiodothyronine (T3) production in the unicellular Tetrahymena.

PubMed

Csaba, G; Pállinger, Eva

2011-09-01

The aim of the experiments was to study the regulation of triiodothyronine (T3) production in the unicellular Tetrahymena. Untreated and troph-hormone treated specimen were prepared and in different timepoints T3 content was measured and compared by immunocytochemical flow cytometry. 0.1 or 0.001 IU TSH in tryptone-yeast medium stimulated T3 synthesis at 10, 20, 30 min, but does not stimulate after 1 h. The overlapping gonadotropic hormone (GTH) also did it, however only at 10 min. In Losina salt solution (physiological for Tetrahymena) the effect was weaker, however outer amino acid source was not absolutely needed for the production of the hormone. The results show that the TSH regulation of thyroid hormone synthesis (storage, secretion) and troph-hormone overlap can be deduced to a unicellular level. This may allow the hypothesis that the endocrine mechanisms proved at a low level of phylogeny are preserved for the higher ranked organisms.

Neuronal 3',3,5-triiodothyronine (T3) uptake and behavioral phenotype of mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-Herndon-Dudley syndrome.

PubMed

Wirth, Eva K; Roth, Stephan; Blechschmidt, Cristiane; Hölter, Sabine M; Becker, Lore; Racz, Ildiko; Zimmer, Andreas; Klopstock, Thomas; Gailus-Durner, Valerie; Fuchs, Helmut; Wurst, Wolfgang; Naumann, Thomas; Bräuer, Anja; de Angelis, Martin Hrabé; Köhrle, Josef; Grüters, Annette; Schweizer, Ulrich

2009-07-29

Thyroid hormone transport into cells requires plasma membrane transport proteins. Mutations in one of these, monocarboxylate transporter 8 (MCT8), have been identified as underlying cause for the Allan-Herndon-Dudley syndrome, an X-linked mental retardation in which the patients also present with abnormally high 3',3,5-triiodothyronine (T(3)) plasma levels. Mice deficient in Mct8 replicate the thyroid hormone abnormalities observed in the human condition. However, no neurological deficits have been described in mice lacking Mct8. Therefore, we subjected Mct8-deficient mice to a comprehensive immunohistochemical, neurological, and behavioral screen. Several behavioral abnormalities were found in the mutants. Interestingly, some of these behavioral changes are compatible with hypothyroidism, whereas others rather indicate hyperthyroidism. We thus hypothesized that neurons exclusively dependent on Mct8 are in a hypothyroid state, whereas neurons expressing other T(3) transporters become hyperthyroid, if they are exposed directly to the high plasma T(3). The majority of T(3) uptake in primary cortical neurons is mediated by Mct8, but pharmacological inhibition suggested functional expression of additional T(3) transporter classes. mRNAs encoding six T(3) transporters, including L-type amino acid transporters (LATs), were coexpressed with Mct8 in isolated neurons. We then demonstrated Lat2 expression in cultured neurons and throughout murine brain development. In contrast, LAT2 is expressed in microglia in the developing human brain during gestation, but not in neurons. We suggest that lack of functional complementation by alternative thyroid hormone transporters in developing human neurons precipitates the devastating neurodevelopmental phenotype in MCT8-deficient patients, whereas Mct8-deficient mouse neurons are functionally complemented by other transporters, for possibly Lat2.

Pituitary resistance to thyroid hormone associated with a base mutation in the hormone-binding domain of the human 3,5,3'-triiodothyronine receptor-beta.

PubMed

Sasaki, S; Nakamura, H; Tagami, T; Miyoshi, Y; Nogimori, T; Mitsuma, T; Imura, H

1993-05-01

Point mutations in the human T3 receptor-beta (TR beta) gene causing single amino acid substitutions have been identified in several different kindreds with generalized resistance to thyroid hormone. Until now, no study has been reported on the TR gene in cases of pituitary resistance (PRTH). In the present study, we analyzed the TR beta gene in a 30-yr-old Japanese female with PRTH. She exhibited clinical features of hyperthyroidism, elevated serum thyroid hormone levels accompanied by inappropriately increased secretion of TSH, mildly elevated basal metabolic rate, and increased urinary excretion of hydroxyproline. No pituitary tumor was detected. DNA fragments of exons 3-8 of the genomic TR beta gene were generated by the polymerase chain reaction and analyzed by a single stranded conformation polymorphism method. Exon 7 of the patient's TR beta gene showed an abnormal band, suggesting the existence of mutation(s). By subcloning and sequencing the DNA, a point mutation was identified in one allele at nucleotide 1297 (C to T), which altered the 333rd amino acid, arginine, to tryptophan. Neither of her apparently normal parents had any mutations of the TR beta gene. In vitro translation products of the mutant TR beta gene showed remarkably decreased T3-binding activity (Ka, 2.1 x 10(8) M-1; normal TR beta Ka, 1.1 x 10(10) M-1). Since the molecular defect detected in a patient with PRTH is similar to that seen in subjects with generalized resistance to thyroid hormone, both types of the syndrome may represent a continuous spectrum of the same etiological defect with variable tissue resistance to thyroid hormone.

Simultaneous quantification of T4, T3, rT3, 3,5-T2 and 3,3'-T2 in larval zebrafish (Danio rerio) as a model to study exposure to polychlorinated biphenyls.

PubMed

Chen, Xiaopeng; Walter, Kyla M; Miller, Galen W; Lein, Pamela J; Puschner, Birgit

2018-06-01

Environmental toxicants that interfere with thyroid hormone (TH) signaling can impact growth and development in animals and humans. Zebrafish represent a model to study chemically induced TH disruption, prompting the need for sensitive detection of THs. Simultaneous quantification of 3,3',5-triiodo-l-thyronine (T3), thyroxine (T4), 3,3',5'-triiodo-l-thyronine (rT3), 3,5-diiodo-l-thyronine (3,5-T2) and 3,3'-diiodo-l-thyronine (3,3'-T2) in zebrafish larvae was achieved by ultra-performance liquid chromatography-tandem mass spectrometry in positive ion mode. Solid-phase extraction with SampliQ cartridges and derivatization with 3 m hydrochloric acid in n-butanol reduced matrix effects. Derivatized compounds were separated on an Acquity UPLC BEH C 18 column with mobile phases consisting of 0.1% acetic acid in deionized water and 0.1% acetic acid in methanol. The limits of detection ranged from 0.5 to 0.6 pg injected on column. The method was validated by evaluating recovery (77.1-117.2%), accuracy (87.3-123.9%) and precision (0.5-12.4%) using diluted homogenized zebrafish embryos spiked with all target compounds. This method was then applied to zebrafish larvae collected after 114 h of exposure to polychlorinated biphenyls (PCBs), including PCB 28, PCB 66 and PCB 95, or the technical mixture Aroclor 1254. Exposure to PCB 28 and PCB 95 increased the T4:T3 ratio and decreased the T3:rT3 ratio, demonstrating that this method can effectively detect PCB-induced alterations in THs. Copyright © 2018 John Wiley & Sons, Ltd.

Determining Baseline Stress-Related Hormone Values in Large Cetaceans

DTIC Science & Technology

2014-09-30

reconstructed chemical profiles provided a unique window into stress-related hormone (cortisol, aldosterone , T3 and T4) concentrations and...Stress-related hormone radioimmunoassay technique Cortisol, aldosterone , hormones thyroxine (T4) and triiodothyronine (T3) levels in each identified...contaminant concentrations will be calculated using Pearson correlation coefficients. These measurements will include all hormones ( aldosterone , T3

Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism?

PubMed

Biondi, Bernadette; Wartofsky, Leonard

2012-07-01

Levothyroxine therapy is the traditional lifelong replacement therapy for hypothyroid patients. Over the last several years, new evidence has led clinicians to evaluate the option of combined T(3) and T(4) treatment to improve the quality of life, cognition, and peripheral parameters of thyroid hormone action in hypothyroidism. The aim of this review is to assess the physiological basis and the results of current studies on this topic. We searched Medline for reports published with the following search terms: hypothyroidism, levothyroxine, triiodothyronine, thyroid, guidelines, treatment, deiodinases, clinical symptoms, quality of life, cognition, mood, depression, body weight, heart rate, cholesterol, bone markers, SHBG, and patient preference for combined therapy. The search was restricted to reports published in English since 1970, but some reports published before 1970 were also incorporated. We supplemented the search with records from personal files and references of relevant articles and textbooks. Parameters analyzed included the rationale for combination treatment, the type of patients to be selected, the optimal T(4)/T(3) ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action. The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in hypothyroid patients. Further prospective randomized controlled studies are needed to clarify this important issue. Innovative formulations of the thyroid hormones will be required to mimic a more perfect thyroid hormone replacement therapy than is currently available.

Determining Baseline Stress-Related Hormone Values in Large Cetaceans

DTIC Science & Technology

2015-09-30

individual whale. These reconstructed chemical profiles provided a unique window into stress-related hormone (cortisol, aldosterone , T3 and T4...stored under nitrogen at -30 °C. Stress-related hormone radioimmunoassay technique Cortisol, aldosterone , hormones thyroxine (T4) and...coefficients. These measurements will include all hormones ( aldosterone , T3, T4, and cortisol) as well as contaminants. The age trends for the 6 hormones will

Molecular Aspects of Thyroid Hormone Actions

PubMed Central

Cheng, Sheue-Yann; Leonard, Jack L.; Davis, Paul J.

2010-01-01

Cellular actions of thyroid hormone may be initiated within the cell nucleus, at the plasma membrane, in cytoplasm, and at the mitochondrion. Thyroid hormone nuclear receptors (TRs) mediate the biological activities of T3 via transcriptional regulation. Two TR genes, α and β, encode four T3-binding receptor isoforms (α1, β1, β2, and β3). The transcriptional activity of TRs is regulated at multiple levels. Besides being regulated by T3, transcriptional activity is regulated by the type of thyroid hormone response elements located on the promoters of T3 target genes, by the developmental- and tissue-dependent expression of TR isoforms, and by a host of nuclear coregulatory proteins. These nuclear coregulatory proteins modulate the transcription activity of TRs in a T3-dependent manner. In the absence of T3, corepressors act to repress the basal transcriptional activity, whereas in the presence of T3, coactivators function to activate transcription. The critical role of TRs is evident in that mutations of the TRβ gene cause resistance to thyroid hormones to exhibit an array of symptoms due to decreasing the sensitivity of target tissues to T3. Genetically engineered knockin mouse models also reveal that mutations of the TRs could lead to other abnormalities beyond resistance to thyroid hormones, including thyroid cancer, pituitary tumors, dwarfism, and metabolic abnormalities. Thus, the deleterious effects of mutations of TRs are more severe than previously envisioned. These genetic-engineered mouse models provide valuable tools to ascertain further the molecular actions of unliganded TRs in vivo that could underlie the pathogenesis of hypothyroidism. Actions of thyroid hormone that are not initiated by liganding of the hormone to intranuclear TR are termed nongenomic. They may begin at the plasma membrane or in cytoplasm. Plasma membrane-initiated actions begin at a receptor on integrin αvβ3 that activates ERK1/2 and culminate in local membrane actions on

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase.

PubMed

Wirth, Eva K; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-09-01

The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated.

Thyroid hormones and their effects: a new perspective.

PubMed

Hulbert, A J

2000-11-01

The thyroid hormones are very hydrophobic and those that exhibit biological activity are 3',5',3,5-L-tetraiodothyronine (T4), 3',5,3-L-triiodothyronine (T3), 3',5',3-L-triiodothyronine (rT3) and 3,5',-L-diiothyronine (3,5-T2). At physiological pH, dissociation of the phenolic -OH group of these iodothyronines is an important determinant of their physical chemistry that impacts on their biological effects. When non-ionized these iodothyronines are strongly amphipathic. It is proposed that iodothyronines are normal constituents of biological membranes in vertebrates. In plasma of adult vertebrates, unbound T4 and T3 are regulated in the picomolar range whilst protein-bound T4 and T3 are maintained in the nanomolar range. The function of thyroid-hormone-binding plasma proteins is to ensure an even distrubtion throughout the body. Various iodothyronines are produced by three types of membrane-bound cellular deiodinase enzyme systems in vertebrates. The distribution of deiodinases varies between tissues and each has a distinct developmental profile. Thyroid hormones. (1) the nuclear receptor mode is especially important in the thyroid hormone axis that controls plasma and cellular levels of these hormones. (2) These hormones are strongly associated with membranes in tissues and normally rigidify these membranes. (3) They also affect the acyl composition of membrane bilayers and it is suggested that this is due to the cells responding to thyroid-hormone-induced membrane rigidificataion. Both their immediate effects on the physical state of membranes and the consequent changes in membrane composition result in several other thyroid hormone effects. Effects on metabolism may be due primarily to membrane acyl changes. There are other actions of thyroid hormones involving membrane receptors and influences on cellular interactions with the extracellulara matrix. The effects of thyroid hormones are reviewed and appear to b combinations of these various modes of action. During

Thyroid hormone modulates insulin-like growth factor-I(IGF-I) and IGF-binding protein-3, without mediation by growth hormone, in patients with autoimmune thyroid diseases.

PubMed

Inukai, T; Takanashi, K; Takebayashi, K; Fujiwara, Y; Tayama, K; Takemura, Y

1999-10-01

The expression and synthesis of insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) are regulated by various hormones and nutritional conditions. We evaluated the effects of thyroid hormones on serum levels of IGF-I and IGFBP-3 levels in patients with autoimmune thyroid diseases including 54 patients with Graves' disease and 17 patients with Hashimoto's thyroiditis, and in 32 healthy age-matched control subjects. Patients were subdivided into hyperthyroid, euthyroid and hypothyroid groups that were untreated, or were treated with methylmercaptoimidazole (MMI) or L-thyroxine (L-T4). Serum levels of growth hormone (GH), IGF-I and IGFBP-3 were determined by radioimmunoassay. Serum GH levels did not differ significantly between the hyperthyroid and the age-matched euthyroid patients with Graves' disease. The serum levels of IGF-I and IGFBP-3 showed a significant positive correlation in the patients (R=0.616, P<0.001). The levels of both IGF-I and IFGBP-3 were significantly higher in the hyperthyroid patients with Graves' disease or in those with Hashimoto's thyroiditis induced by excess L-T4 administration than in control subjects. Patients with hypothyroid Graves' disease induced by the excess administration of MMI showed significantly lower IGFBP-3 levels as compared to those in healthy controls (P<0.05). Levels of IGFBP-3, but not IGF-I levels, showed a significant positive correlation with the levels of free T4 and free T3. In Graves' disease, levels of TPOAb, but not of TRAb, showed a significant positive correlation with IGFBP-3. We conclude that in patients with autoimmune thyroid diseases, thyroid hormone modulates the synthesis and/or the secretion of IGF-I and IGFBP-3, and this function is not mediated by GH.

Comparative effect of Citrus sinensis and carbimazole on serum T4, T3 and TSH levels.

PubMed

Uduak, Okon Akpan; Ani, Elemi John; Etoh, Emmauel Columba Inyang; Macstephen, Adienbo Ologbagno

2014-05-01

There are previous independent reports on the anti-thyroid property of Citrus sinensis. This isoflavones and phenolic acid-rich natural agent is widely consumed as dietary supplement, thus the need to investigate its comparative effect with a standard anti-thyroid drug on T4, T3 and thyroid stimulating hormone (TSH) levels. To compare the effect of Citrus sinensis and carbimazole (CARB) on blood levels of thyroid hormones (T4 and T3) and TSH. Male wistar albino rats weighing 100-150 g were employed in this research. The rats were randomly assigned to four groups of seven rats per group. Group I served as control and were administered distilled water while groups II-IV were administered with 1500 mg/kg of Citrus sinensis (fresh orange juice; FOJ), 0.1 μg/g of levothyroxine (LVT) and 0.01 mg/g of CARB, respectively, per oral once daily for 28 days. The animals were sacrificed under chloroform anaesthesia and blood sample collected by cardiac puncture and processed by standard method to obtain serum. TSH, T4 and T3 were assayed with the serum using ARIA II automated radioimmunoassay instrument. The results showed that TSH level was significantly (P < 0.05) decreased in LVT treated group compared with the FOJ group. T4 was significantly (P < 0.05) decreased in the FOJ and CARB groups compared with the control and LVT groups. LVT significantly increased T4 when compared with FOJ group. T3 was significantly (P < 0.05) decreased in the CARB group compared with the control. These findings suggest that FOJ alters thyroid hormones metabolism to reduce their serum levels with a compensatory elevations of TSH level in a direction similar to CARB.

Comparative effect of Citrus sinensis and carbimazole on serum T4, T3 and TSH levels

PubMed Central

Uduak, Okon Akpan; Ani, Elemi John; Etoh, Emmauel Columba Inyang; Macstephen, Adienbo Ologbagno

2014-01-01

Background: There are previous independent reports on the anti-thyroid property of Citrus sinensis. This isoflavones and phenolic acid-rich natural agent is widely consumed as dietary supplement, thus the need to investigate its comparative effect with a standard anti-thyroid drug on T4, T3 and thyroid stimulating hormone (TSH) levels. Objective: To compare the effect of Citrus sinensis and carbimazole (CARB) on blood levels of thyroid hormones (T4 and T3) and TSH. Materials and Methods: Male wistar albino rats weighing 100-150 g were employed in this research. The rats were randomly assigned to four groups of seven rats per group. Group I served as control and were administered distilled water while groups II-IV were administered with 1500 mg/kg of Citrus sinensis (fresh orange juice; FOJ), 0.1 μg/g of levothyroxine (LVT) and 0.01 mg/g of CARB, respectively, per oral once daily for 28 days. The animals were sacrificed under chloroform anaesthesia and blood sample collected by cardiac puncture and processed by standard method to obtain serum. TSH, T4 and T3 were assayed with the serum using ARIA II automated radioimmunoassay instrument. Results: The results showed that TSH level was significantly (P < 0.05) decreased in LVT treated group compared with the FOJ group. T4 was significantly (P < 0.05) decreased in the FOJ and CARB groups compared with the control and LVT groups. LVT significantly increased T4 when compared with FOJ group. T3 was significantly (P < 0.05) decreased in the CARB group compared with the control. Conclusion: These findings suggest that FOJ alters thyroid hormones metabolism to reduce their serum levels with a compensatory elevations of TSH level in a direction similar to CARB. PMID:25013255

Polybrominated diphenyl ether (PBDE) exposures and thyroid hormones in children at age 3 years.

PubMed

Vuong, Ann M; Braun, Joseph M; Webster, Glenys M; Thomas Zoeller, R; Hoofnagle, Andrew N; Sjödin, Andreas; Yolton, Kimberly; Lanphear, Bruce P; Chen, Aimin

2018-08-01

Polybrominated diphenyl ethers (PBDEs) reduce serum thyroid hormone concentrations in animal studies, but few studies have examined the impact of early-life PBDE exposures on thyroid hormone disruption in childhood. We used data from 162 mother-child pairs from the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, OH). We measured PBDEs in maternal serum at 16 ± 3 weeks gestation and in child serum at 1-3 years. Thyroid hormones were measured in serum at 3 years. We used multiple informant models to investigate associations between prenatal and early-life PBDE exposures and thyroid hormone levels at age 3 years. Prenatal PBDEs were associated with decreased thyroid stimulating hormone (TSH) levels at age 3 years. A 10-fold increase in prenatal ∑PBDEs (BDE-28, -47, -99, -100, and -153) was associated with a 27.6% decrease (95% CI -40.8%, -11.3%) in TSH. A ten-fold increase in prenatal ∑PBDEs was associated with a 0.25 pg/mL (0.07, 0.43) increase in free triiodothyronine (FT 3 ). Child sex modified associations between prenatal PBDEs and thyroid hormones, with significant decrements in TSH among females and decreased free T 4 (FT 4 ) in males. Prenatal ∑PBDEs were not associated with TT 4 , FT 4 , or total T 3 . These findings suggest an inverse relationship between prenatal ∑PBDEs and TSH at 3 years. Associations may be sexually dimorphic, with an inverse relationship between prenatal BDE-47 and -99 and TSH in females and null associations among males. Copyright © 2018 Elsevier Ltd. All rights reserved.

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase

PubMed Central

Wirth, Eva K.; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-01-01

Background The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). Objective: To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). Methods We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Conclusions Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated. PMID:26601078

Thyroid hormone metabolism and environmental chemical exposure

PubMed Central

2012-01-01

Background Polychlorinated dioxins and –furans (PCDD/Fs) and polychlorinated-biphenyls (PCBs) are environmental toxicants that have been proven to influence thyroid metabolism both in animal studies and in human beings. In recent years polybrominated diphenyl ethers (PBDEs) also have been found to have a negative influence on thyroid hormone metabolism. The lower brominated flame retardants are now banned in the EU, however higher brominated decabromo-diphenyl ether (DBDE) and the brominated flame retardant hexabromocyclododecane (HBCD) are not yet banned. They too can negatively influence thyroid hormone metabolism. An additional brominated flame retardant that is still in use is tetrabromobisphenol-A (TBBPA), which has also been shown to influence thyroid hormone metabolism. Influences of brominated flame retardants, PCDD/F’s and dioxin like-PCBs (dl-PCB’s) on thyroid hormone metabolism in adolescence in the Netherlands will be presented in this study and determined if there are reasons for concern to human health for these toxins. In the period 1987-1991, a cohort of mother-baby pairs was formed in order to detect abnormalities in relation to dioxin levels in the perinatal period. The study demonstrated that PCDD/Fs were found around the time of birth, suggesting a modulation of the setpoint of thyroid hormone metabolism with a higher 3,3’, 5,5’tetrathyroxine (T4) levels and an increased thyroid stimulating hormone (TSH). While the same serum thyroid hormone tests (- TSH and T4) were again normal by 2 years of age and were still normal at 8-12 years, adolescence is a period with extra stress on thyroid hormone metabolism. Therefore we measured serum levels of TSH, T4, 3,3’,5- triiodothyronine (T3), free T4 (FT4), antibodies and thyroxine-binding globulin (TBG) in our adolescent cohort. Methods Vena puncture was performed to obtain samples for the measurement of thyroid hormone metabolism related parameters and the current serum dioxin (PCDD/Fs), PCB

Effects of potassium iodide in concentrations of TSH, tT3 and tT4 in serum of subjects with sporotrichosis.

PubMed

Ramírez Soto, Max Carlos

2014-08-01

The saturated potassium iodide solution (SSKI) as treatment for sporotrichosis may cause hypothyroidism by suppressing the synthesis of thyroid hormones (tT3 and tT4 ) and the iodine excess could lead to thyrotoxicosis. Evaluating the changes in serum levels of TSH, tT3 and tT4 in euthyroid patients with sporotrichosis treated with SSKI. For the selection of euthyroid patients, TSH, tT3 and tT4 concentrations were measured for those adults and children diagnosed with sporotrichosis. Each paediatric patient was administered SSKI orally in increasing doses of 2-20 drops/3 times/day and 4-40 drops/3 times/day in adults. Serum concentrations of TSH, tT3 and tT4 were measured 20 days after started the treatment and 15 days posttreatment. Eight euthyroid patients aged between 2 to 65 years old were included. After 20 days of treatment, two suffered subclinical hypothyroidism, one developed subclinical hyperthyroidism, and one hyperthyroxinaemia euthyroid. At 15 days posttreatment only four patients were evaluated and all serum levels of TSH, tT3 and tT4 were normal. Some euthyroid patients with sporotrichosis can develop hyperthyroidism or subclinical iodine-induced hypothyroidism, during the administration of 3 or 6 g SSKI/day. © 2014 Blackwell Verlag GmbH.

Hippocampal gene expression of deiodinases 2 and 3 and effects of 3,5-diiodo-L-thyronine T2 in mouse depression paradigms.

PubMed

Markova, Natalyia; Chernopiatko, Anton; Schroeter, Careen A; Malin, Dmitry; Kubatiev, Aslan; Bachurin, Sergey; Costa-Nunes, João; Steinbusch, Harry M W; Strekalova, Tatyana

2013-01-01

Central thyroid hormone signaling is important in brain function/dysfunction, including affective disorders and depression. In contrast to 3,3',5-triiodo-L-thyronine (T3), the role of 3,5-diiodo-L-thyronine (T2), which until recently was considered an inactive metabolite of T3, has not been studied in these pathologies. However, both T3 and T2 stimulate mitochondrial respiration, a factor counteracting the pathogenesis of depressive disorder, but the cellular origins in the CNS, mechanisms, and kinetics of the cellular action for these two hormones are distinct and independent of each other. Here, Illumina and RT PCR assays showed that hippocampal gene expression of deiodinases 2 and 3, enzymes involved in thyroid hormone regulation, is increased in resilience to stress-induced depressive syndrome and after antidepressant treatment in mice that might suggest elevated T2 and T3 turnover in these phenotypes. In a separate experiment, bolus administration of T2 at the doses 750 and 1,500 mcg/kg but not 250 mcg/kg in naive mice reduced immobility in a two-day tail suspension test in various settings without changing locomotion or anxiety. This demonstrates an antidepressant-like effect of T2 that could be exploited clinically. In a wider context, the current study suggests important central functions of T2, whose biological role only lately is becoming to be elucidated.

Cytosolic T3-binding protein modulates dynamic alteration of T3-mediated gene expression in cells.

PubMed

Takeshige, Keiko; Sekido, Takashi; Kitahara, Jun-ichirou; Ohkubo, Yousuke; Hiwatashi, Dai; Ishii, Hiroaki; Nishio, Shin-ichi; Takeda, Teiji; Komatsu, Mitsuhisa; Suzuki, Satoru

2014-01-01

μ-Crystallin (CRYM) is also known as NADPH-dependent cytosolic T3-binding protein. A study using CRYM-null mice suggested that CRYM stores triiodothyronine (T3) in tissues. We previously established CRYM-expressing cells derived from parental GH3 cells. To examine the precise regulation of T3-responsive genes in the presence of CRYM, we evaluated serial alterations of T3-responsive gene expression by changing pericellular T3 concentrations in the media. We estimated the constitutive expression of three T3-responsive genes, growth hormone (GH), deiodinase 1 (Dio1), and deiodinase 2 (Dio2), in two cell lines. Subsequently, we measured the responsiveness of these three genes at 4, 8, 16, and 24 h after adding various concentrations of T3. We also estimated the levels of these mRNAs 24 and 48 h after removing T3. The levels of constitutive expression of GH and Dio1 were low and high in C8 cells, respectively, while Dio2 expression was not significantly different between GH3 and C8 cells. When treated with T3, Dio2 expression was significantly enhanced in C8 cells, while there were no differences in GH or Dio1 expression between GH3 and C8 cell lines. In contrast, removal of T3 retained the mRNA expression of GH and Dio2 in C8 cells. These results suggest that CRYM expression increases and sustains the T3 responsiveness of genes in cells, especially with alteration of the pericellular T3 concentration. The heterogeneity of T3-related gene expression is dependent on cellular CRYM expression in cases of dynamic changes in pericellular T3 concentration.

[Effect of aceclofenac on thyroid hormone binding and thyroid function].

PubMed

Nadler, K; Buchinger, W; Semlitsch, G; Pongratz, R; Rainer, F

2000-01-01

Influences of non-steroidal anti-inflammatory drugs (NSAID) on concentrations of thyroid hormones are known for a long time. These effects could be explained with interference between NSAIDs and thyroid hormone binding. We investigated the effects of a single dose of aceclofenac on thyroid function and thyroid hormone binding in 18 healthy volunteers. Serum levels of free thyroid hormones (FT3, FT4) and thyrotropin (TSH) were measured with commercial available kids and thyroid hormone binding was estimated with a specially modified horizontal argarose-gel-electrophoresis prior to and 2 hours after receiving a single dose of aceclofenac. We found a significant decrease in T3 binding on TBG and a significant increase of albumin-bound T3. All other investigated thyroid hormone binding parameters, FT3 and FT4, showed no significant changes. We conclude that aceclofenac leads to a significant redistribution of T3 protein binding. These effects seem to be explained by T3 displacement from TBG induced by aceclofenac.

Association between thyroid hormones and TRAIL.

PubMed

Bernardi, Stella; Bossi, Fleur; Toffoli, Barbara; Giudici, Fabiola; Bramante, Alessandra; Furlanis, Giulia; Stenner, Elisabetta; Secchiero, Paola; Zauli, Giorgio; Carretta, Renzo; Fabris, Bruno

2017-11-01

Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis-inducing ligand) might have a role in the regulation of body weight and metabolism. Interestingly, thyroid hormones seem to increase TRAIL tissue expression. This study aimed at evaluating whether overt thyroid disorders affected circulating TRAIL levels. TRAIL circulating levels were measured in euthyroid, hyperthyroid, and hypothyroid patients before and after thyroid function normalization. Univariate and multivariate analyses were performed to evaluate the correlation between thyroid hormones and TRAIL. Then, the stimulatory effect of both triiodothyronine (T3) and thyroxine (T4) on TRAIL was evaluated in vitro on peripheral blood mononuclear cells. Circulating levels of TRAIL significantly increased in hyperthyroid and decreased in hypothyroid patients as compared to controls. Once thyroid function was restored, TRAIL levels normalized. There was an independent association between TRAIL and both fT3 and fT4. Consistent with these findings, T3 and T4 stimulated TRAIL release in vitro. Here we show that thyroid hormones are associated with TRAIL expression in vivo and stimulate TRAIL expression in vitro. Given the overlap between the metabolic effects of thyroid hormones and TRAIL, this work sheds light on the possibility that TRAIL might be one of the molecules mediating thyroid hormones peripheral effects. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Hippocampal Gene Expression of Deiodinases 2 and 3 and Effects of 3,5-Diiodo-L-Thyronine T2 in Mouse Depression Paradigms

PubMed Central

Markova, Natalyia; Chernopiatko, Anton; Schroeter, Careen A.; Malin, Dmitry; Kubatiev, Aslan; Bachurin, Sergey; Costa-Nunes, João; Steinbusch, Harry M. W.; Strekalova, Tatyana

2013-01-01

Central thyroid hormone signaling is important in brain function/dysfunction, including affective disorders and depression. In contrast to 3,3′,5-triiodo-L-thyronine (T3), the role of 3,5-diiodo-L-thyronine (T2), which until recently was considered an inactive metabolite of T3, has not been studied in these pathologies. However, both T3 and T2 stimulate mitochondrial respiration, a factor counteracting the pathogenesis of depressive disorder, but the cellular origins in the CNS, mechanisms, and kinetics of the cellular action for these two hormones are distinct and independent of each other. Here, Illumina and RT PCR assays showed that hippocampal gene expression of deiodinases 2 and 3, enzymes involved in thyroid hormone regulation, is increased in resilience to stress-induced depressive syndrome and after antidepressant treatment in mice that might suggest elevated T2 and T3 turnover in these phenotypes. In a separate experiment, bolus administration of T2 at the doses 750 and 1500 mcg/kg but not 250 mcg/kg in naive mice reduced immobility in a two-day tail suspension test in various settings without changing locomotion or anxiety. This demonstrates an antidepressant-like effect of T2 that could be exploited clinically. In a wider context, the current study suggests important central functions of T2, whose biological role only lately is becoming to be elucidated. PMID:24386638

Regulation of hormone release by cultured cells from a thyrotropin-growth hormone-secreting pituitary tumor. Direct inhibiting effects of 3,5,3'-triiodothyronine and dexamethasone on thyrotropin secretion.

PubMed

Lamberts, S W; Oosterom, R; Verleun, T; Krenning, E P; Assies, H

1984-08-01

The regulation of TSH and GH secretion was investigated in cultured tumor cells prepared from a mixed TSH/GH secreting pituitary tumor. The tumor tissue had been removed transsphenoidally from a patient with hyperthyroidism and inappropriately high serum TSH levels and acromegaly. TSH and GH secretion by cultured cells were stimulated in a parallel way by TRH (300 nM) and LHRH (50 nM), but were unaffected by bromocriptine (10 nM). Exposure of the tumor cells to dexamethasone (0.1 microM) or T3 (50 nM) had differential effects on hormone secretion. GH secretion was greatly stimulated by dexamethasone, but unaffected by T3. TSH secretion was inhibited both by T3 and by dexamethasone. So, T3 and glucocorticoids inhibit TSH release by the human pituitary tumor cells studied at least partly by means of a direct effect.

Effects of thyroid hormone manipulation on pre-nuptial molt, luteinizing hormone and testicular growth in male white-crowned sparrows (Zonotrichia leuchophrys gambelii).

PubMed

Pérez, Jonathan H; Meddle, Simone L; Wingfield, John C; Ramenofsky, Marilyn

2018-01-01

Most seasonal species rely on the annual change in day length as the primary cue to appropriately time major spring events such as pre-nuptial molt and breeding. Thyroid hormones are thought to be involved in the regulation of both of these spring life history stages. Here we investigated the effects of chemical inhibition of thyroid hormone production using methimazole, subsequently coupled with either triiodothyronine (T3) or thyroxine (T4) replacement, on the photostimulation of pre-nuptial molt and breeding in Gambel's white-crowned sparrows (Zonotrichia leuchophrys gambelii). Suppression of thyroid hormones completely prevented pre-nuptial molt, while both T3 and T4 treatment restored normal patterns of molt in thyroid hormone-suppressed birds. Testicular recrudescence was blocked by methimazole, and restored by T4 but not T3, in contrast to previous findings demonstrating central action of T3 in the photostimulation of breeding. Methimazole and replacement treatments elevated plasma luteinizing hormone levels compared to controls. These data are partially consistent with existing theories on the role of thyroid hormones in the photostimulation of breeding, while highlighting the possibility of additional feedback pathways. Thus we suggest that regulation of the hypothalamic pituitary gonad axis that controls breeding may be more complex than previously considered. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[Thyroid hormone metabolism and action].

PubMed

Köhrle, Josef

2004-05-01

Reductive deiodination of thyroid hormones at the phenolic and tyrosyl ring leads to the activation or inactivation of the thyromimetic activity inherent to thyroid hormones. Alterations in the activities of the three selenocysteine-containing enzymes, the iodothyronine deiodinases, have been reported during development and in specific cells and tissues of the adult organism. Furthermore, pathophysiological changes in the deiodinase expression lead to therapeutically relevant disturbances of the homeostasis of thyroid hormones. Metabolisation of thyroid hormones by conjugation of their phenolic 4'-OH group, their alanine side chain or cleavage of their diphenylether bridge also contributes to both local and systemic supply of thyromimetic activity or hormone degradation. Further components mediating the pleiotropic action of thyroid hormones in part include redundant T3 receptors, binding and transport proteins, metabolising enzymes and T3-regulated gene products. This is achieved in a finely tuned manner with multiple feedback control, malfunction or complete failure of individual components and networks involved in the iodothyronine metabolism and thyroid hormone action can thus be compensated or prevented.

Exogenous T3 toxicosis following consumption of a contaminated weight loss supplement.

PubMed

D'Arcy, R; McDonnell, M; Spence, K; Courtney, C H

2017-01-01

A 42-year-old male presented with a one-week history of palpitations and sweating episodes. The only significant history was of longstanding idiopathic dilated cardiomyopathy. Initial ECG demonstrated a sinus tachycardia. Thyroid function testing, undertaken as part of the diagnostic workup, revealed an un-measureable thyroid-stimulating hormone (TSH) and free thyroxine (T 4 ). Upon questioning the patient reported classical thyrotoxic symptoms over the preceding weeks. Given the persistence of symptoms free tri-iodothyronine (T 3 ) was measured and found to be markedly elevated at 48.9 pmol/L (normal range: 3.1-6.8 pmol/L). No goitre or nodular disease was palpable in the neck. Historically there had never been any amiodarone usage. Radionucleotide thyroid uptake imaging ( 123 I) demonstrated significantly reduced tracer uptake in the thyroid. Upon further questioning the patient reported purchasing a weight loss product online from India which supposedly contained sibutramine. He provided one of the tablets and laboratory analysis confirmed the presence of T 3 in the tablet. Full symptomatic resolution and normalised thyroid function ensued upon discontinuation of the supplement. Free tri-iodothyronine (T 3 ) measurement may be useful in the presence of symptoms suggestive of thyrotoxicosis with discordant thyroid function tests.Thyroid uptake scanning can be a useful aid to differentiating exogenous hormone exposure from endogenous hyperthyroidism.Ingestion of thyroid hormone may be inadvertent in cases of exogenous thyrotoxicosis.Medicines and supplements sourced online for weight loss may contain thyroxine (T 4 ) or T 3 and should be considered as a cause of unexplained exogenous hyperthyroidism.

A Recessive Mutation Resulting in a Disabling Amino Acid Substitution (T194R) in the LHX3 Homeodomain Causes Combined Pituitary Hormone Deficiency

PubMed Central

Bechtold-Dalla Pozza, Susanne; Hiedl, Stefan; Roeb, Julia; Lohse, Peter; Malik, Raleigh E.; Park, Soyoung; Durán-Prado, Mario; Rhodes, Simon J.

2012-01-01

Background/Aims Recessive mutations in the LHX3 ho-meodomain transcription factor gene are associated with developmental disorders affecting the pituitary and nervous system. We describe pediatric patients with combined pituitary hormone deficiency (CPHD) who harbor a novel mutation in LHX3. Methods Two female siblings from related parents were examined. Both patients had neonatal complications. The index patient had CPHD featuring deficiencies of GH, LH, FSH, PRL, and TSH, with later onset of ACTH deficiency. She also had a hypoplastic anterior pituitary, respiratory distress, hearing impairment, and limited neck rotation. The LHX3 gene was sequenced and the biochemical properties of the predicted altered proteins were characterized. Results A novel homozygous mutation predicted to change amino acid 194 from threonine to arginine (T194R) was detected in both patients. This amino acid is conserved in the DNA-binding homeodomain. Computer modeling predicted that the T194R change would alter the homeodomain structure. The T194R protein did not bind tested LHX3 DNA recognition sites and did not activate the α-glycoprotein and PRL target genes. Conclusion The T194R mutation affects a critical residue in the LHX3 protein. This study extends our understanding of the phenotypic features, molecular mechanism, and developmental course associated with mutations in the LHX3 gene. PMID:22286346

The lipid fraction of human milk initiates adipocyte differentiation in 3T3-L1 cells.

PubMed

Fujisawa, Yasuko; Yamaguchi, Rie; Nagata, Eiko; Satake, Eiichiro; Sano, Shinichiro; Matsushita, Rie; Kitsuta, Kazunobu; Nakashima, Shinichi; Nakanishi, Toshiki; Nakagawa, Yuichi; Ogata, Tsutomu

2013-09-01

The prevalence of childhood obesity has increased worldwide over the past decade. Despite evidence that human milk lowers the risk of childhood obesity, the mechanism is not fully understood. We investigated the direct effect of human milk on differentiation of 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were treated with donated human milk only or the combination of the standard hormone mixture; insulin, dexamethasone (DEX), and 3-isobututyl-1-methylxanthine (IBMX). Furthermore, the induction of preadipocyte differentiation by extracted lipids from human milk was tested in comparison to the cells treated with lipid extracts from infant formula. Adipocyte differentiation, specific genes as well as formation of lipid droplets were examined. We clearly show that lipids present in human milk initiate 3T3-L1 preadipocyte differentiation. In contrast, this effect was not observed in response to lipids present in infant formula. The initiation of preadipocyte differentiation by human milk was enhanced by adding the adipogenic hormone, DEX or insulin. The expression of late adipocyte markers in Day 7 adipocytes that have been induced into differentiation with human milk lipid extracts was comparable to those in control cells initiated by a standard adipogenic hormone cocktail. These results demonstrate that human milk contains bioactive lipids that can initiate preadipocyte differentiation in the absence of the standard adipogenic compounds via a unique pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

Congenital combined pituitary hormone deficiency attributable to a novel PROP1 mutation (467insT).

PubMed

Nose, Osamu; Tatsumi, Keita; Nakano, Yukiko; Amino, Nobuyuki

2006-04-01

Combined pituitary hormone deficiency (CPHD) is an anterior pituitary disorder, commonly resulting in growth retardation. PROP1 gene mutations appear to be frequently responsible for CPHD, particularly in Middle and Eastern Europe and the Americas, but few cases have been reported in Japan. Two sisters (aged 8.4 and 4.3 years at presentation) exhibited proportional short stature from about 2 years of age. Genetic analysis determined the nature and location of mutations. Pituitary size by magnetic resonance imaging (MRI) indicated only slight hypoplasia, while hormone analysis revealed deficiencies in secretion of growth hormone (GH), thyroid stimulating hormone, prolactin and gonadotropins; adrenocortinotropin secretion appeared adequate. Genetic analysis revealed a novel familial inherited PROP1 mutation. A unique insertion mutation was found in codon 156 (467insT) located in the transcription-activating region of the PROP1 gene. The resulting PROP1 protein (191 amino acids) would lack the transcription activation domain and consequently be non-functional. Gene analysis suggested that the siblings had inherited a unique autosomal recessive PROP1 gene mutation resulting in severe GH deficiency and subsequent growth retardation.

Developmental and Thyroid Hormone Regulation of the DNA Methyltransferase 3a Gene in Xenopus Tadpoles

PubMed Central

Kyono, Yasuhiro; Sachs, Laurent M.; Bilesimo, Patrice; Wen, Luan

2016-01-01

Thyroid hormone is essential for normal development in vertebrates. In amphibians, T3 controls metamorphosis by inducing tissue-specific gene regulation programs. A hallmark of T3 action is the modification of chromatin structure, which underlies changes in gene transcription. We found that mRNA for the de novo DNA methyltransferase (DNMT) dnmt3a, but not dnmt1, increased in the brain of Xenopus tadpoles during metamorphosis in parallel with plasma [T3]. Addition of T3 to the rearing water caused a time-dependent increase in dnmt3a mRNA in tadpole brain, tail, and hind limb. By analyzing data from a genome-wide analysis of T3 receptor (TR) binding in tadpole tail, we identified several putative T3 response elements (TREs) within the dnmt3a locus. Using in vitro DNA binding, transient transfection-reporter, and chromatin immunoprecipitation assays for TRs, we identified two functional TREs at −7.1 kb and +5.1 kb relative to the dnmt3a transcription start site. Sequence alignment showed that these TREs are conserved between two related frog species, X. laevis and X. tropicalis, but not with amniotes. Our previous findings showed that this gene is directly regulated by liganded TRs in mouse brain, and whereas the two mouse TREs are conserved among Eutherian mammals, they are not conserved in Xenopus species. Thus, although T3 regulation of dnmt3a may be an ancient pathway in vertebrates, the genomic sites responsible for hormone regulation may have diverged or arisen by convergent evolution. We hypothesize that direct T3 regulation of dnmt3a may be an important mechanism for modulating global changes in DNA methylation. PMID:27779916

Thyroid stimulating hormone and serum, plasma, and platelet brain-derived neurotrophic factor during a 3-month follow-up in patients with major depressive disorder.

PubMed

Baek, Ji Hyun; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Nierenberg, Andrew A; Lee, Dongsoo; Heo, Jung-Yoon; Jeon, Hong Jin

2014-12-01

Thyroid dysfunction and elevated thyroid stimulating hormone (TSH) are common in patients with depression. TSH might exert its function in the brain through blood levels of brain-derived neurotrophic factor (BDNF). BDNF decreases during depressed states and normalize after treatment. The gap is that the association between TSH and BDNF in patients with major depressive disorder (MDD) is unknown. We studied 105 subjects ≥18 years of age with MDD and measured serum, plasma, and platelet BDNF at baseline, 1 month and 3 months during antidepressant treatment. Other baseline measurements included hypothalamic-pituitary-thyroid axis hormones such as TSH, triiodothyronine (T3) and thyroxine (T4); hypothalamic-pituitary-adrenal (HPA) axis hormones and hypothalamic-pituitary-gonadal (HPG) axis hormones and prolactin. Linear mixed model effect analyses revealed that baseline TSH level was negatively associated with changes of serum BDNF from baseline to 3 months (F=7.58, p=0.007) after adjusting for age, sex, and body mass index, but was not associated with plasma and platelet BDNF. In contrast, T3 and T4, HPA axis hormones, HPG axis hormones, and prolactin were not associated with serum, plasma, or platelet BDNF levels. Patients in the highest quartile of TSH showed significantly lower serum BDNF than in the other quartiles (F=4.54, p=0.038), but no significant differences were found based on T3 and T4 levels. TSH was only measured at baseline. Higher TSH is associated with lower baseline and reduced the increase of serum BDNF levels during antidepressant treatment in patients with MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

ErbB2 and EGFR are downmodulated during the differentiation of 3T3-L1 preadipocytes.

PubMed

Pagano, Eleonora; Calvo, Juan Carlos

2003-10-15

The expression of receptors belonging to the epidermal growth factor receptor subfamily has been largely studied these last years in epithelial cells mainly as involved in cell proliferation and malignant progression. Although much work has focused on the role of these growth factor receptors in the differentiation of a variety of tissues, there is little information in regards to normal stromal cells. We investigated erbB2 expression in the murine fibroblast cell line Swiss 3T3L1, which naturally or hormonally induced undergoes adipocyte differentiation. We found that the Swiss 3T3-L1 fibroblasts express erbB2, in addition to EGFR, and in a quantity comparable to or even greater than the breast cancer cell line T47D. Proliferating cells increased erbB2 and EGFR levels when reaching confluence up to 4- and 10-fold, respectively. This expression showed a significant decrease when growth-arrested cells were stimulated to differentiate with dexamethasone and isobutyl-methylxanthine. Differentiated cells presented a decreased expression of both erbB2 and EGFR regardless of whether the cells were hormonally or spontaneously differentiated. EGF stimulation of serum-starved cells increased erbB2 tyrosine phosphorylation and retarded erbB2 migration in SDS-PAGE, suggesting receptor association and activation. Heregulin-alpha1 and -beta1, two EGF related factors, had no effect on erbB2 or EGFR phosphorylation. Although 3T3-L1 cells expressed heregulin, its specific receptors, erbB3 and erbB4, were not found. This is the first time in which erbB2 is reported to be expressed in an adipocytic cell line which does not depend on non EGF family growth factors (thyroid hormone, growth hormone, etc.) to accomplish adipose differentiation. Since erbB2 and EGFR expression were downmodulated as differentiation progressed it is conceivable that a mechanism of switching from a mitogenic to a differentiating signaling pathway may be involved, through regulation of the expression of these

Free and total thyroid hormones in humans at extreme altitude

NASA Astrophysics Data System (ADS)

Basu, Minakshi; Pal, K.; Malhotra, A. S.; Prasad, R.; Sawhney, R. C.

1995-03-01

Alterations in circulatory levels of total T4 (TT4), total T3 (TT3), free T4 (FT4), free T3 (FT3), thyrotropin (TSH) and T3 uptake (T3U) were studied in male and female sea-level residents (SLR) at sea level, in Armed forces personnel staying at high altitude (3750 m) for prolonged duration (acclimatized lowlanders, ALL) and in high-altitude natives (HAN). Identical studies were also performed on male ALL who trekked to an extreme altitude of 5080 m and stayed at an altitude of more than 6300 m for about 6 months. The total as well as free thyroid hormones were found to be significantly higher in ALL and HAN as compared to SLR values. Both male as well as female HAN had higher levels of thyroid hormones. The rise in hormone levels in different ALL ethnic groups drawn from amongst the southern and northern parts of the country was more or less identical. In both HAN and ALL a decline in FT3 and FT4 occurred when these subjects trekked at subzero temperatures to extreme altitude of 5080 m but the levels were found to be higher in ALL who stayed at 6300 m for a prolonged duration. Plasma TSH did not show any appreciable change at lower altitudes but was found to be decreased at extreme altitude. The increase in thyroid hormones at high altitude was not due to an increase in hormone binding proteins, since T3U was found to be higher at high altitudes. A decline in TSH and hormone binding proteins and an increase in the free moiety of the hormones is indicative of a subtle degree of tissue hyperthyroidism which may be playing an important role in combating the extreme cold and hypoxic environment of high altitudes.

Thyroid hormones regulate anxiety in the male mouse.

PubMed

Buras, Alexander; Battle, Loxley; Landers, Evan; Nguyen, Tien; Vasudevan, Nandini

2014-02-01

Thyroid hormone levels are implicated in mood disorders in the adult human but the mechanisms remain unclear partly because, in rodent models, more attention has been paid to the consequences of perinatal hypo and hyperthyroidism. Thyroid hormones act via the thyroid hormone receptor (TR) α and β isoforms, both of which are expressed in the limbic system. TR's modulate gene expression via both unliganded and liganded actions. Though the thyroid hormone receptor (TR) knockouts and a transgenic TRα1 knock-in mouse have provided us valuable insight into behavioral phenotypes such as anxiety and depression, it is not clear if this is because of the loss of unliganded actions or liganded actions of the receptor or due to locomotor deficits. We used a hypothyroid mouse model and supplementation with tri-iodothyronine (T3) or thyroxine (T4) to investigate the consequences of dysthyroid hormone levels on behaviors that denote anxiety. Our data from the open field and the light-dark transition tests suggest that adult onset hypothyroidism in male mice produces a mild anxiogenic effect that is possibly due to unliganded receptor actions. T3 or T4 supplementation reverses this phenotype and euthyroid animals show anxiety that is intermediate between the hypothyroid and thyroid hormone supplemented groups. In addition, T3 but not T4 supplemented animals have lower spine density in the CA1 region of the hippocampus and in the central amygdala suggesting that T3-mediated rescue of the hypothyroid state might be due to lower neuronal excitability in the limbic circuit. Copyright © 2013 Elsevier Inc. All rights reserved.

Peripheral thyroid hormone levels and hepatic thyroid hormone deiodinase gene expression in dairy heifers on the day of ovulation and during the early peri-implantation period.

PubMed

Meyerholz, Marie Margarete; Mense, Kirsten; Linden, Matthias; Raliou, Mariam; Sandra, Olivier; Schuberth, Hans-Joachim; Hoedemaker, Martina; Schmicke, Marion

2016-09-08

Before the onset of fetal thyroid hormone production, the transplacental delivery of maternal thyroid hormones is necessary for embryonic and fetal development. Therefore, the adaptation of maternal thyroid hormone metabolism may be important for pregnancy success and embryo survival. The aims of this study were to determine the thyroid hormone levels during the early peri-implantation period until day 18 and on the day of ovulation, to determine whether pregnancy success is dependent on a "normothyroid status" and to determine whether physiological adaptations in maternal thyroid hormone metabolism occur, which may be necessary to provide sufficient amounts of biologically active T3 to support early pregnancy. Therefore, blood samples obtained on the day of ovulation (day 0) and days 14 and 18 of the Holstein-Friesian heifers (n = 10) during the respective pregnant, non-pregnant and negative control cycles were analyzed for thyroid-stimulating-hormone (TSH), thyroxine (T4) and triiodothyronine (T3). Liver biopsies (day 18) from pregnant and respective non-pregnant heifers were analyzed for mRNA expression of the most abundant hepatic thyroid hormone deiodinase (DIO1) by real time qPCR. Although liver DIO1 mRNA expression did not differ between the pregnant and non-pregnant heifers on day 18, the serum concentrations of TSH and T3 on day 18 were higher in non-pregnant heifers compared to pregnant heifers (P < 0.05). Moreover, T3 decreased between day 0 and 18 in pregnant heifers (P < 0.001). In conclusion, no associations between thyroid hormone patterns on day 18 and pregnancy success were detected. During the early peri-implantation period, TSH and T3 may be affected by the pregnancy status because both TSH and T3 were lower on day 18 in pregnant heifers compared to non-pregnant dairy heifers. In further studies, the thyroid hormone axis should be evaluated throughout the entire gestation to confirm these data and identify other possible effects of

Increased Procurement of Thoracic Donor Organs After Thyroid Hormone Therapy.

PubMed

Novitzky, Dimitri; Mi, Zhibao; Collins, Joseph F; Cooper, David K C

2015-01-01

Hormonal therapy to the brain-dead organ donor can include thyroid hormone (triiodothyronine [T3] or levothyroxine [T4]), antidiuretic hormone, corticosteroids, or insulin. There has been a controversy on whether thyroid hormone enables more organs to be procured. Data on 63,593 donors of hearts and lungs (2000-2009) were retrospectively reviewed. Documentation on T3/T4 was available in all donors (study 1), and in 40,124 details of all 4 hormones were recorded (study 2). In this cohort, group A (23,022) received T3/T4 and group B (17,102) no T3/T4. Univariate analyses and multiple regressions were performed. Posttransplant graft and recipient survival at 1 and 12 months were compared. In study 1, 30,962 donors received T3/T4, with 36.59% providing a heart and 20.05% providing 1 or both lungs. Of the 32,631 donors who did not receive T3/T4, only 29.62% provided a heart and 14.61% provided lungs, an increase of 6.97% hearts and 5.44% lungs from T3/T4-treated donors (both P < 0.0001). In study 2, 34.99% of group A provided a heart and 20.99% provided lungs. In group B only 25.76% provided a heart and 15.09% provided lungs, an increase of 9.23% (hearts) and 5.90% (lungs), respectively, in group A (both P < 0.0001). The results of multiple regression analyses indicated a beneficial effect of T3/T4 on heart (P < 0.0001) and lung (P < 0.0001) procurement independent of other factors. T3/T4 therapy to the donor was associated with either improved posttransplant graft and recipient survival or no difference in survival. T3/T4 therapy results in more transplantable hearts and lungs, with no detriment to posttransplant graft or recipient survival. Copyright © 2015 Elsevier Inc. All rights reserved.

Alternate pathways of thyroid hormone metabolism.

PubMed

Wu, Sing-Yung; Green, William L; Huang, Wen-Sheng; Hays, Marguerite T; Chopra, Inder J

2005-08-01

The major thyroid hormone (TH) secreted by the thyroid gland is thyroxine (T(4)). Triiodothyronine (T(3)), formed chiefly by deiodination of T(4), is the active hormone at the nuclear receptor, and it is generally accepted that deiodination is the major pathway regulating T(3) bioavailability in mammalian tissues. The alternate pathways, sulfation and glucuronidation of the phenolic hydroxyl group of iodothyronines, the oxidative deamination and decarboxylation of the alanine side chain to form iodothyroacetic acids, and ether link cleavage provide additional mechanisms for regulating the supply of active hormone. Sulfation may play a general role in regulation of iodothyronine metabolism, since sulfation of T(4) and T(3) markedly accelerates deiodination to the inactive metabolites, reverse triiodothyronine (rT(3)) and T(2). Sulfoconjugation is prominent during intrauterine development, particularly in the precocial species in the last trimester including humans and sheep, where it may serve both to regulate the supply of T(3), via sulfation followed by deiodination, and to facilitate maternal-fetal exchange of sulfated iodothyronines (e.g., 3,3'-diiodothyronine sulfate [T(2)S]). The resulting low serum T(3) may be important for normal fetal development in the late gestation. The possibility that T(2)S or its derivative, transferred from the fetus and appearing in maternal serum or urine, can serve as a marker of fetal thyroid function is being studied. Glucuronidation of TH often precedes biliary-fecal excretion of hormone. In rats, stimulation of glucuronidation by various drugs and toxins may lead to lower T(4) and T(3) levels, provocation of thyrotropin (TSH) secretion, and goiter. In man, drug induced stimulation of glucuronidation is limited to T(4), and does not usually compromise normal thyroid function. However, in hypothyroid subjects, higher doses of TH may be required to maintain euthyroidism when these drugs are given. In addition, glucuronidates and

Prolonged weightlessness effect on postflight plasma thyroid hormones

NASA Technical Reports Server (NTRS)

Leach, C. S.; Johnson, P. C.; Driscoll, T. B.

1977-01-01

Blood drawn before and after spaceflight from the nine Skylab astronauts showed a statistically significant increase in mean plasma thyroxine (T-4) of 1.4 micro g/dl and in thyroid-stimulating hormone (TSH) of 4 microunits ml. Concurrent triiodothyronine (T-3) levels decreased 27 ng/dl indicating inhibited conversion of T-4 to T-3. The T-3 decrease is postulated to be a result of the increased cortisol levels noted during and following each mission. These results confirm the thyroidal changes noted after the shorter Apollo flights and show that thyroid hormone levels change during spaceflight.

A hormone map of human immune cells showing the presence of adrenocorticotropic hormone, triiodothyronine and endorphin in immunophenotyped white blood cells

PubMed Central

Pállinger, Éva; Csaba, György

2008-01-01

The amounts of adrenocorticotropic hormone (ACTH), endorphin and triiodothyronine (T3) in twenty-six blood samples from men and women who were healthy or had non-haematological diseases were determined by flow cytometry. Lymphocytes were immunophenotyped using monoclonal antibodies against cell surface antigens, and monocytes and granulocytes were separated by their size and granularity (using forward-scatter versus side-scatter dot plots). Each hormone was found in each cell type. The hormone content of lymphocytes was balanced, but the concentration of ACTH was significantly lower in activated T cells, that of endorphin was significantly lower in natural killer (NK) cells, and that of T3 was lower in both cell types compared with values for all lymphocytes. Monocytes and granulocytes contained very significantly more hormones than lymphocytes or monocytes. The concentration of endorphin was an order of magnitude higher in granulocytes than in monocytes or lymphocytes, reflecting the pain-relieving role of granulocytes during inflammation. Compared with monocytes, in granulocytes there was a higher concentration of ACTH and a lower concentration of T3, which suggests selective hormone production by these cells. PMID:18005034

Foetal immune programming: hormones, cytokines, microbes and regulatory T cells.

PubMed

Hsu, Peter; Nanan, Ralph

2014-10-01

In addition to genetic factors, environmental cues play important roles in shaping the immune system. The first environment that the developing foetal immune system encounters is the uterus. Although physically the mother and the foetus are separated by the placental membranes, various factors such as hormones and cytokines may provide "environmental cues" to the foetal immune system. Additionally, increasing evidence suggests that prenatal maternal environmental factors, particularly microbial exposure, might significantly influence the foetal immune system, affecting long-term outcomes, a concept termed foetal immune programming. Here we discuss the potential mediators of foetal immune programming, focusing on the role of pregnancy-related hormones, cytokines and regulatory T cells, which play a critical role in immune tolerance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The thyroid hormone triiodothyronine controls macrophage maturation and functions: protective role during inflammation.

PubMed

Perrotta, Cristiana; Buldorini, Marcella; Assi, Emma; Cazzato, Denise; De Palma, Clara; Clementi, Emilio; Cervia, Davide

2014-01-01

The endocrine system participates in regulating macrophage maturation, although little is known about the modulating role of the thyroid hormones. In vitro results demonstrate a negative role of one such hormone, triiodothyronine (T3), in triggering the differentiation of bone marrow-derived monocytes into unpolarized macrophages. T3-induced macrophages displayed a classically activated (M1) signature. A T3-induced M1-priming effect was also observed on polarized macrophages because T3 reverses alternatively activated (M2) activation, whereas it enhances that of M1 cells. In vivo, circulating T3 increased the content of the resident macrophages in the peritoneal cavity, whereas it reduced the content of the recruited monocyte-derived cells. Of interest, T3 significantly protected mice against endotoxemia induced by lipopolysaccharide i.p. injection; in these damaged animals, decreased T3 levels increased the recruited (potentially damaging) cells, whereas restoring T3 levels decreased recruited and increased resident (potentially beneficial) cells. These data suggest that the anti-inflammatory effect of T3 is coupled to the modulation of peritoneal macrophage content, in a context not fully explained by the M1/M2 framework. Thyroid hormone receptor expression analysis and the use of different thyroid hormone receptor antagonists suggest thyroid hormone receptor β1 as the major player mediating T3 effects on macrophages. The novel homeostatic link between thyroid hormones and the pathophysiological role of macrophages opens new perspectives on the interactions between the endocrine and immune systems. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Effects of oral administration of levothyroxine sodium on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone in healthy adult mares.

PubMed

Sommardahl, Carla S; Frank, Nicholas; Elliott, Sarah B; Webb, Latisha L; Refsal, Kent R; Denhart, Joseph W; Thompson, Donald L

2005-06-01

To determine the effects of levothyroxine sodium (L-T4) on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone (TRH) in euthyroid horses. 12 healthy adult mares. 8 horses received an incrementally increasing dosage of L-T4 (24, 48, 72, or 96 mg of L-T4/d) for weeks 1 to 8. Each dose was provided for 2 weeks. Four additional horses remained untreated. Serum concentrations of total triiodothyronine (tT3), total thyroxine (tT4), free T3 (fT3), free T4 (fT4), and thyroid-stimulating hormone (TSH) were measured in samples obtained at weeks 0, 2, 4, 6, and 8; 1.2 mg of TRH was then administered i.v., and serum concentrations of thyroid gland hormones were measured 2 and 4 hours after injection. Serum reverseT3 (rT3) concentration was also measured in the samples collected at weeks 0 and 8. Treated horses lost a significant amount of weight (median, 19 kg). Significant treatment-by-time effects were detected for serum tT3, tT4, fT3, fT4, and TSH concentrations, and serum tT4 concentrations were positively correlated (r, 0.95) with time (and therefore dosage) in treated horses. Mean +/- SD serum rT3 concentration significantly increased in treated horses (3.06 +/- 0.51 nmol/L for week 8 vs 0.74 +/- 0.22 nmol/L for week 0). Serum tT3, tT4, fT3, and TSH concentrations in response to TRH injections differed significantly between treated and untreated horses. Administration of levothyroxine sodium increased serum tT4 concentrations and blunted responses toTRH injection in healthy euthyroid horses.

Tissue-specific thyroid hormone regulation of gene transcripts encoding iodothyronine deiodinases and thyroid hormone receptors in striped parrotfish (Scarus iseri).

PubMed

Johnson, Kaitlin M; Lema, Sean C

2011-07-01

In fish as in other vertebrates, the diverse functions of thyroid hormones are mediated at the peripheral tissue level through iodothyronine deiodinase (dio) enzymes and thyroid hormone receptor (tr) proteins. In this study, we examined thyroid hormone regulation of mRNAs encoding the three deiodinases dio1, dio2 and dio3 - as well as three thyroid hormone receptors trαA, trαB and trβ - in initial phase striped parrotfish (Scarus iseri). Parrotfish were treated with dissolved phase T(3) (20 nM) or methimazole (3 mM) for 3 days. Treatment with exogenous T(3) elevated circulating T(3), while the methimazole treatment depressed plasma T(4). Experimentally-induced hyperthyroidism increased the relative abundance of transcripts encoding trαA and trβ in the liver and brain, but did not affect trαB mRNA levels in either tissue. In both sexes, methimazole-treated fish exhibited elevated dio2 transcripts in the liver and brain, suggesting enhanced outer-ring deiodination activity in these tissues. Accordingly, systemic hyperthyroidism elevated relative dio3 transcript levels in these same tissues. In the gonad, however, patterns of transcript regulation were distinctly different with elevated T(3) increasing mRNAs encoding dio2 in testicular and ovarian tissues and dio3, trαA and trαB in the testes only. Thyroid hormone status did not affect dio1 transcript abundance in the liver, brain or gonads. Taken as a whole, these results demonstrate that thyroidal status influences relative transcript abundance for dio2 and dio3 in the liver, provide new evidence for similar patterns of dio2 and dio3 mRNA regulation in the brain, and make evident that fish exhibit tr subtype-specific transcript abundance changes to altered thyroid status. Copyright © 2011 Elsevier Inc. All rights reserved.

[The relation between the low T3 syndrome in the clinical course of myocardial infarction and heart failure].

PubMed

Frączek, Magdalena Maria; Gackowski, Andrzej; Przybylik-Mazurek, Elwira; Nessler, Jadwiga

2016-06-01

It has been proven that either excess or deficiency of thyroid hormones has harmful influence on the cardiovascular system function. On the other hand, severe systemic conditions like myocardial infarction or severe heart failure may affect thyroid hormones secretion and their peripheral conversion, leading to low T3 syndrome. Amongst many mechanisms causing T4 to T3 conversion disturbances, important role plays decreased activity of D1 deiodinase and increased activity of D3 deiodinase. The animal research confirmed that thyroid hormones influence cardiomiocytes phenotype and morphology. They inhibit inflammation, apoptosis and cardiac remodelling after myocardial infarction. It was also proven that free triiodothyronine similarly to brain natriuretic peptide predict long-term prognosis in chronic and acute heart failure patients. Potential influence of low T3 syndrome on the course of myocardial infarction and heart failure may have significant impact on the future research on individualization of myocardial infarction and heart failure treatment depending on patient's thyroid status. © 2016 MEDPRESS.

Thyroid hormone deiodination in birds.

PubMed

Darras, Veerle M; Verhoelst, Carla H J; Reyns, Geert E; Kühn, Eduard R; Van der Geyten, Serge

2006-01-01

Because the avian thyroid gland secretes almost exclusively thyroxine (T4), the availability of receptor-active 3,3',5-triiodothyronine (T3) has to be regulated in the extrathyroidal tissues, essentially by deiodination. Like mammals and most other vertebrates, birds possess three types of iodothyronine deiodinases (D1, D2, and D3) that closely resemble their mammalian counterparts, as shown by biochemical characterization studies in several avian species and by cDNA cloning of the three enzymes in chicken. The tissue distribution of these deiodinases has been studied in detail in chicken at the level of activity and mRNA expression. More recently specific antibodies were used to study cellular localization at the protein level. The abundance and distribution of the different deiodinases shows substantial variation during embryonic development and postnatal life. Deiodination in birds is subject to regulation by hormones from several endocrine axes, including thyroid hormones, growth hormone and glucocorticoids. In addition, deiodination is also influenced by external parameters, such as nutrition, temperature, light and also a number of environmental pollutants. The balance between the outer and inner ring deiodination resulting from the impact of all these factors ultimately controls T3 availability.

Regulation of fish growth hormone transcription.

PubMed

Farchi-Pisanty, O; Hackett, P B; Moav, B

1995-09-01

Regulation of endogenous fish growth hormone transcription was studied using carp pituitaries in vitro. It was demonstrated that thyroid hormone (T3) and 9-cis retinoic acid have increased the steady state levels of growth hormone messenger RNA in pituitary cells, as compared with beta-actin messenger RNA levels. In contrast, estrogen failed to increase growth hormone mRNA levels. The possible involvement of thyroid hormone receptor in pituitary gene expression was demonstrated by in situ localization of both growth hormone mRNA and thyroid hormone receptor mRNA in the pituitaries as early as 4 days after fertilization.

A cross-sectional study on the associations of insulin resistance with sex hormone, abnormal lipid metabolism in T2DM and IGT patients

PubMed Central

Wang, Xiaoxia; Xian, Tongzhang; Jia, Xiaofan; Zhang, Lina; Liu, Li; Man, Fuli; Zhang, Xianbo; Zhang, Jie; Pan, Qi; Guo, Lixin

2017-01-01

Abstract Type 2 diabetes mellitus (T2DM) is a long-term metabolic disorder. It is characterized by hyperglycemia, insulin resistance (IR), and relative impairment in insulin secretion. IR plays a major role in the pathogenesis of T2DM. Many previous studies have investigated the relationship between estrogen, androgen, and obesity, but few focused on the relationship between sex hormones, abnormal lipid metabolism, and IR. The goal for the present study was to identify the association of IR with sex hormone, abnormal lipid metabolism in type 2 diabetes, and impaired glucose tolerance (IGT) patients. In total 13,400 participants were analyzed based on the results of the glucose tolerance test. Using a cross-sectional study, we showed the relationship between IR and the level of sex hormones among 3 different glucose tolerance states: normal control people, IGT, and T2DM patients. We also analyzed the relationship between IR and abnormal lipid metabolism. Significantly, luteinizing, progesterone, estradiol, prolactin, and follicle-stimulating hormone levels decreased in T2DM and IGT patients compared with those in normal control people. The association between IR and lipid metabolism disorders in T2DM and IGT patients was also observed. Our clinical findings may offer new insights into understanding the mechanism of metabolic disorders and in new therapeutic methods for the treatment of the prevalence of type 2 diabetes. PMID:28658166

Different Types of Luciferase Reporters Show Distinct Susceptibility to T3-Evoked Downregulation.

PubMed

Kollár, Anna; Kvárta-Papp, Zsuzsanna; Egri, Péter; Gereben, Balázs

2016-01-01

The firefly luciferase reporter protein is a crucial tool for studies targeting a broad range of biological questions. Importantly, luciferase assays are also widely used to explore mechanisms underlying thyroid hormone dependent regulation of gene expression. However, it was demonstrated that the firefly luciferase reporter is subject to triiodothyronine (T3)-evoked, promoter independent downregulation that is mediated by the thyroid hormone receptor. Since this effect can interfere with readout accuracy, the study aimed to find luciferase reporters that are not susceptible to this phenomenon. Luciferase reporter constructs were generated under the control of a minimal thymidine kinase (TK) promoter and transiently transfected into JEG-3 cells to test their activity upon T3 treatment. Activity of the TK-(dCpG)Luc encoding a synthetic (dCpG)Luciferase and TK-NanoLuc expressing the NanoLuc reporter was not significantly changed by T3 treatment while the firefly luciferase control was suppressed by ∼2.6-fold. T3 also downregulated the activity of Renilla luciferase by ∼30%. Novel types of luciferase reporters, especially the synthetic (dCpG)Luciferase, can be more accurate to study T3-regulated gene expression than the classical firefly luciferase reporter. Renilla luciferase, a popular transfection control of dual luciferase assays, should be used with caution in conditions with T3 treatment.

Steroid Sex Hormones, Sex Hormone-Binding Globulin, and Diabetes Incidence in the Diabetes Prevention Program.

PubMed

Mather, K J; Kim, C; Christophi, C A; Aroda, V R; Knowler, W C; Edelstein, S E; Florez, J C; Labrie, F; Kahn, S E; Goldberg, R B; Barrett-Connor, E

2015-10-01

Steroid sex hormones and SHBG may modify metabolism and diabetes risk, with implications for sex-specific diabetes risk and effects of prevention interventions. This study aimed to evaluate the relationships of steroid sex hormones, SHBG and SHBG single-nucleotide polymorphisms (SNPs) with diabetes risk factors and with progression to diabetes in the Diabetes Prevention Program (DPP). This was a secondary analysis of a multicenter randomized clinical trial involving 27 U.S. academic institutions. The study included 2898 DPP participants: 969 men, 948 premenopausal women not taking exogenous sex hormones, 550 postmenopausal women not taking exogenous sex hormones, and 431 postmenopausal women taking exogenous sex hormones. Participants were randomized to receive intensive lifestyle intervention, metformin, or placebo. Associations of steroid sex hormones, SHBG, and SHBG SNPs with glycemia and diabetes risk factors, and with incident diabetes over median 3.0 years (maximum, 5.0 y). T and DHT were inversely associated with fasting glucose in men, and estrone sulfate was directly associated with 2-hour post-challenge glucose in men and premenopausal women. SHBG was associated with fasting glucose in premenopausal women not taking exogenous sex hormones, and in postmenopausal women taking exogenous sex hormones, but not in the other groups. Diabetes incidence was directly associated with estrone and estradiol and inversely with T in men; the association with T was lost after adjustment for waist circumference. Sex steroids were not associated with diabetes outcomes in women. SHBG and SHBG SNPs did not predict incident diabetes in the DPP population. Estrogens and T predicted diabetes risk in men but not in women. SHBG and its polymorphisms did not predict risk in men or women. Diabetes risk is more potently determined by obesity and glycemia than by sex hormones.

Thyroid Hormone in the Clinic and Breast Cancer.

PubMed

Hercbergs, Aleck; Mousa, Shaker A; Leinung, Matthew; Lin, Hung-Yun; Davis, Paul J

2018-06-01

There is preclinical and recent epidemiological evidence that thyroid hormone supports breast cancer. These observations raise the issue of whether management of breast cancer in certain settings should include consideration of reducing the possible contribution of thyroid hormone to the advancement of the disease. In a preliminary experience, elimination of the clinical action of endogenous L-thyroxine (T 4 ) in patients with advanced solid tumors, including breast cancer, has favorably affected the course of the cancer, particularly when coupled with administration of exogenous 3,5,3'-triiodo-L-thyronine (T 3 ) (euthyroid hypothyroxinemia). We discuss in the current brief review the possible clinical settings in which to consider whether endogenous thyroid hormone-or exogenous thyroid hormone in the patient with hypothyroidism and coincident breast cancer-is significantly contributing to breast cancer outcome.

Alterations in expression of senescence marker protein-30 gene by 3,3',5-triiodo-L-thyronine (T3).

PubMed

Sar, Pranati; Rath, Bandita; Subudhi, Umakanta; Chainy, Gagan Bihari Nityananda; Supakar, Prakash Chandra

2007-09-01

Thyroid hormone (T3) is essential for normal development, differentiation, and metabolic balance of the body. A toxic dose of T(3) in animals increases the basal metabolic rate and reactive oxygen species production, resulting more oxidative stress through Ca(2+) influx to cytoplasm. Senescence Marker Protein-30 (SMP30) is preferentially expressed in the liver and protects cells against various injuries by enhancement of Ca(2+) efflux to either extra cellular space or intraorganellar spaces through membrane Ca(2+) pump activity. In this paper we report an alteration in the level of SMP30 gene expression using RT-PCR and western blot analysis in T(3) treated female Wistar rats. The results indicate that there is an induction of SMP30 expression during early hours of T(3 )treatment and it declines in severe hyperthyroidism. Therefore, we speculate that SMP30 is regulated by T(3) and might play a protective role in hyperthyroidism.

Impact of Drinking Water Fluoride on Human Thyroid Hormones: A Case- Control Study.

PubMed

Kheradpisheh, Zohreh; Mirzaei, Masoud; Mahvi, Amir Hossein; Mokhtari, Mehdi; Azizi, Reyhane; Fallahzadeh, Hossein; Ehrampoush, Mohammad Hassan

2018-02-08

The elevated fluoride from drinking water impacts on T 3 , T 4 and TSH hormones. The aim was study impacts of drinking water fluoride on T 3 , T 4 and TSH hormones inYGA (Yazd Greater Area). In this case- control study 198 cases and 213 controls were selected. Fluoride was determined by the SPADNS Colorimetric Method. T 3 , T 4 and TSH hormones tested in the Yazd central laboratory by RIA (Radio Immuno Assay) method. The average amount of TSH and T 3 hormones based on the levels of fluoride in two concentration levels 0-0.29 and 0.3-0.5 (mg/L) was statistically significant (P = 0.001 for controls and P = 0.001 for cases). In multivariate regression logistic analysis, independent variable associated with Hypothyroidism were: gender (odds ratio: 2.5, CI 95%: 1.6-3.9), family history of thyroid disease (odds ratio: 2.7, CI 95%: 1.6-4.6), exercise (odds ratio: 5.34, CI 95%: 3.2-9), Diabetes (odds ratio: 3.7, CI 95%: 1.7-8), Hypertension (odds ratio: 3.2, CI 95%: 1.3-8.2), water consumption (odds ratio: 4, CI 95%: 1.2-14). It was found that fluoride has impacts on TSH, T 3 hormones even in the standard concentration of less than 0.5 mg/L. Application of standard household water purification devices was recommended for hypothyroidism.

Human milk and infant formula can induce in vitro adipocyte differentiation in murine 3T3-L1 preadipocytes.

PubMed

Lyle, R E; Corley, J D; McGehee, R E

1998-11-01

The potential of infant diet to influence fat cell development has largely been examined in clinical studies with conflicting results. In this study, the direct effects of two standard infant formulas, Enfamil and Similac, as well as human milk were examined using a well characterized model of adipocyte differentiation, the 3T3-L1 murine preadipocyte cell line. After exposure to a hormonal regimen of insulin, dexamethasone, and 1-methyl-3-isobutylmethylxanthine, these cells undergo a mitotic expansion phase followed by terminal differentiation. On d 4 of hormonal exposure, greater than 95% of 3T3-L1 cells exhibit the morphologic and biochemical characteristics of mature adipocytes. In this study, cells were exposed to control medium, or control medium supplemented with either 10% Enfamil, 10% Similac, 10% human milk (skim or whole), or the standard hormonal regimen. Oil Red O-detectable lipid accumulation, immunocytochemical cell proliferation assays, and activated expression of adipocyte differentiation-specific mRNAs by Northern blot analysis were used to assess the effects of treatment on adipocyte differentiation. Results from each level of assessment revealed that both Enfamil and human milk were as effective as the standard hormonal regimen at stimulating adipocyte differentiation. In contrast, results from treatment with Similac or human skim milk were indistinguishable from control unstimulated cells. This study, demonstrating that Enfamil and human milk are capable of independently inducing in vitro adipocyte differentiation, suggests that diet during infancy could influence body fat development.

Effect of 3,5,3'-Triiodothyronine (T3) administration on dio1 gene expression and T3 metabolism in normal and type 1 deiodinase-deficient mice.

PubMed

Maia, A L; Kieffer, J D; Harney, J W; Larsen, P R

1995-11-01

The type 1 deiodinase (D1) catalyzes the monodeiodination of T4 to produce T3, the active thyroid hormone. In the C3H mouse, hepatic D1 and the dio1 messenger RNA (mRNA) are only 10% that in the C57 strain, the common phenotype. Low activity cosegregated with a series of five GCT repeats located in the 5'-flanking region of the C3H dio1 gene that impaired C3H promoter potency and provided a partial explanation for the lower D1. The present studies were performed to search for additional explanations for low D1 activity in C3H mice. Previous studies have shown that T3 up-regulates the dio1 gene. Therefore, loss of the capacity to respond to endogenous T3 is a possible additional cause of the lower D1 levels in the C3H mice. The hepatic C3H dio1 mRNA increases 10- to 20 fold after T3 administration. The t3 effect occurs at a transplantation level and T3 does not alter the dio1 mRNA half-life. Despite the transcriptional response to T3, no functional thyroid response elements were identified in the 1.5-kilobase 5'-flanking region of either the C57 or C3H dio1 gene. After the same dose of exogenous T3, both dio1 mRNA and D1 of the C3H mouse respond to a greater extent than those of the C57 strain. This can be explained in part by the reduction in T3 clearance due to the lower D1 levels in C3H mice in which higher concentrations of circulating T3 are maintained. The decrease in serum T3 levels and T3 production observed in fasting and systemic illness in both human and experimental animals has been attributed in part to a decrease in hepatic D1. In contrast, despite markedly lower hepatic and renal D1 levels, serum T3 concentrations remain normal in C3H mice. The present studies suggest that the absence of stress-induced hypothalamic-pituitary suppression that allows T4 production to be maintained together with the reduced clearance of T3 and T4 via inner ring deiodination compensate for the D1 deficiency.

Food restriction in young Japanese quails: effects on growth, metabolism, plasma thyroid hormones and mRNA species in the thyroid hormone signalling pathway.

PubMed

Rønning, Bernt; Mortensen, Anne S; Moe, Børge; Chastel, Olivier; Arukwe, Augustine; Bech, Claus

2009-10-01

Young birds, in their post-natal growth period, may reduce their growth and metabolism when facing a food shortage. To examine how such responses can be mediated by endocrine-related factors, we exposed Japanese quail chicks to food restriction for either 2 days (age 6-8 days) or 5 days (age 6-11 days). We then measured growth and resting metabolic rate (RMR), and circulating 3,3',5-triiodo-l-thyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) levels as well as expression patterns of genes involved in growth (insulin-like growth factor-I: IGF-I) and thyroid hormone signalling (thyroid-stimulating hormone-beta: TSHbeta, type II iodothyronine deiodinase: D2, thyroid hormone receptors isoforms: TRalpha and TRbeta). The food-restricted chicks receiving a weight-maintenance diet showed reductions in structural growth and RMR. Plasma levels of both T3 and T4 were reduced in the food-restricted birds, and within the 5 days food-restricted group there was a positive correlation between RMR and T3. IGF-I mRNA showed significantly higher abundance in the liver of ad libitum fed birds at day 8 compared with food-restricted birds. In the brain, TSHbeta mRNA level tended to be lower in food-restricted quails on day 8 compared with controls. Furthermore, TRalpha expression was lower in the brain of food-restricted birds at day 8 compared with birds fed ad libitum. Interestingly, brain D2 mRNA was negatively correlated with plasma T3 levels, tending to increase with the length of food restriction. Overall, our results show that food restriction produced significant effects on circulating thyroid hormones and differentially affected mRNA species in the thyroid hormone signalling pathway. Thus, we conclude that the effects of food restriction observed on growth and metabolism were partly mediated by changes in the endocrine-related factors investigated.

Growth hormone facilitates 5'-azacytidine-induced myogenic but inhibits 5'-azacytidine-induced adipogenic commitment in C3H10T1/2 mesenchymal stem cells.

PubMed

Jia, Dan; Zheng, Weijiang; Jiang, Honglin

2018-06-01

The C3H10T1/2 cells are considered mesenchymal stem cells (MSCs) because they can be induced to become the progenitor cells for myocytes, adipocytes, osteoblasts, and chondrocytes by the DNA methyltransferase inhibitor 5'-azacytidine. In this study, we determined the effect of growth hormone (GH) on the myogenic and adipogenic lineage commitment in C3H10T1/2 cells. The C3H10T1/2 cells were treated with recombinant bovine GH in the presence or absence of 5'-azacytidine for 4 days. The myogenic commitment in C3H10T1/2 cells was assessed by immunostaining them for MyoD, the marker for myoblasts, and by determining their capacity to differentiate into the multinucleated myotubes. The adipogenic commitment in C3H10T1/2 cells was assessed by determining their ability to differentiate into adipocytes. Myotubes and adipocyteswere identified by immunocytochemistry and Oil Red O staining, respectively. C3H10T1/2 cells treated with 5'-azacytidine and GH for 4 days contained a greater percentage of MyoD-positive cells than those treated with 5'-axacytidine alone (P < 0.05). The former generated more myotubes than the latter upon induced myoblast differentiation (P < 0.05). However, C3H10T1/2 cells treated with GH alone did not form any myotubes. C3H10T1/2 cells treated with 5'-azacytidine formed adipocytes upon adipocyte differentiation induction, whereas C3H10T1/2 cells treated with GH alone did not form any adipocytes. C3H10T1/2 cells treated with both 5'-azacytidine and GH formed fewer adipocytes than those treated with 5'-azacytidine alone (P < 0.05). Both GHR and IGF-I mRNA expression in C3H10T1/2 cells were increased by 5'-azacytidine (P < 0.05), but neither was affected by GH. Overall, this study showed that GH enhanced 5'-azacytidine-induced commitment in C3H10T1/2 cells to myoblasts but inhibited 5'-azacytidine-induced commitment to preadipocytes. These results support the possibility that GH stimulates skeletal muscle growth and inhibits adipose

Thyroid hormone therapy in the management of 63,593 brain-dead organ donors: a retrospective analysis.

PubMed

Novitzky, Dimitri; Mi, Zhibao; Sun, Qing; Collins, Joseph F; Cooper, David K C

2014-11-27

Hormonal therapy to the brain-dead potential organ donor can include thyroid hormone (triiodothyronine [T3] or levothyroxine [T4]), corticosteroids, antidiuretic hormone, and insulin. Data on 66,629 donors (2000-2009) were retrospectively reviewed. Documentation on T3/T4 was available in 63,593 (study 1), but 23,469 had incomplete documentation of other hormones. In 40,124, details of all four hormones were recorded (study 2). In this cohort, group A (received T3/T4) consisted of 23,022, and group B (no T3/T4) consisted of 17,102 donors. A multivariate analysis was performed to determine whether age, sex, ethnicity, cause of death, body mass index, Organ Procurement Organization region, or other hormonal therapy influenced procurement. Posttransplantation organ graft survival at 1 and 12 months was compared. In study 1, 30,962 (48.69%) received T3/T4, providing a mean of 3.35 organs per donor, and 32,631 (51.31%) did not receive T3/T4, providing a mean of 2.97 organs per donor, an increase of 12.8% of organs from T3/T4-treated donors (P<0.0001). In study 2, group A provided a mean of 3.31 organs per donor and group B provided a mean of 2.87 organs per donor, an increase of 15.3% in group A (P<0.0001). T3/T4 therapy was associated with procurement of significantly greater numbers of hearts, lungs, kidneys, pancreases, and intestines, but not livers. Multivariate analysis indicated a beneficial effect of T3/T4 independent of other factors (P<0.0001). T3/T4 therapy of the donor was associated with improved posttransplantation graft survival or no difference in survival, except for pancreas recipient (but not graft) survival at 12 months in study 2. T3/T4 therapy results in more transplantable organs, with no detriment to posttransplantation graft survival.

Utilizing mass spectrometry imaging to map the thyroid hormones triiodothyronine and thyroxine in Xenopus tropicalis tadpoles.

PubMed

Goto-Inoue, Naoko; Sato, Tomohiko; Morisasa, Mizuki; Kashiwagi, Akihiko; Kashiwagi, Keiko; Sugiura, Yuki; Sugiyama, Eiji; Suematsu, Makoto; Mori, Tsukasa

2018-02-01

Thyroid hormones are not only responsible for thermogenesis and energy metabolism in animals, but also have an important role in cell differentiation and development. Amphibian metamorphosis provides an excellent model for studying the remodeling of the body. This metamorphic organ remodeling is induced by thyroid hormones, and a larval body is thus converted into an adult one. The matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS) imaging technology is expected to be a suitable tool for investigating small bioreactive molecules. The present study describes the distribution of the thyroid hormones, i.e., triiodothyronine (T3) and thyroxine (T4) and their inactive form reverse T3 (rT3) in Xenopus tropicalis tadpoles using two different types of imaging techniques, MS/MS and Fourier transform (FT)-MS imaging. As a result of MS/MS imaging, we demonstrated that T3 was mainly distributed in the gills. T4 was faintly localized in the eyes, inner gills, and intestine during metamorphosis. The intensity of T3 in the gills and the intensity of T4 in the body fluids were increased during metamorphosis. Moreover, the localization of the inactive form rT3 was demonstrated to be separate from T3, namely in the intestine and muscles. In addition, FT-MS imaging could utilize simultaneous imaging including thyroid hormone. This is the first report to demonstrate the molecular distribution of thyroid hormones themselves and to discriminate T3, T4, and rT3 in animal tissues.

Thyroid hormones and fetal brain development.

PubMed

Pemberton, H N; Franklyn, J A; Kilby, M D

2005-08-01

Thyroid hormones are intricately involved in the developing fetal brain. The fetal central nervous system is sensitive to the maternal thyroid status. Critical amounts of maternal T3 and T4 must be transported across the placenta to the fetus to ensure the correct development of the brain throughout ontogeny. Severe mental retardation of the child can occur due to compromised iodine intake or thyroid disease. This has been reported in areas of the world with iodine insufficiency, New Guinea, and also in mother with thyroid complications such as hypothyroxinaemia and hyperthyroidism. The molecular control of thyroid hormones by deiodinases for the activation of thyroid hormones is critical to ensure the correct amount of active thyroid hormones are temporally supplied to the fetus. These hormones provide timing signals for the induction of programmes for differentiation and maturation at specific stages of development. Understanding these molecular mechanisms further will have profound implications in the clinical management of individuals affected by abnormal maternal of fetal thyroid status.

Complex Actions of Thyroid Hormone Receptor Antagonist NH-3 on Gene Promoters in Different Cell Lines

PubMed Central

Shah, Vanya; Nguyen, Phuong; Nguyen, Ngoc-Ha; Togashi, Marie; Scanlan, Thomas S.; Baxter, John D.; Webb, Paul

2014-01-01

It is desirable to obtain new antagonists for thyroid hormone (TRs) and other nuclear receptors (NRs). We previously used X-ray structural models of TR ligand binding domains (LBDs) to design compounds, such as NH-3, that impair coactivator binding to activation function 2 (AF-2) and block thyroid hormone (triiodothyronine, T3) actions. However, TRs bind DNA and are transcriptionally active without ligand. Thus, NH-3 could modulate TR activity via effects on other coregulator interaction surfaces, such as activation function (AF-1) and corepressor binding sites. Here, we find that NH-3 blocks TR-LBD interactions with coactivators and corepressors and also inhibits activities of AF-1 and AF-2 in transfections. While NH-3 lacks detectable agonist activity at T3-activated genes in GC pituitary cells it nevertheless activates spot 14 (S14) in HTC liver cells with the latter effect accompanied by enhanced histone H4 acetylation and coactivator recruitment at the S14 promoter. Surprisingly, T3 promotes corepressor recruitment to target promoters. NH-3 effects vary; we observe transient recruitment of N-CoR to S14 in GC cells and dismissal and rebinding of N-CoR to the same promoter in HTC cells. We propose that NH-3 will generally behave as an antagonist by blocking AF-1 and AF-2 but that complex effects on coregulator recruitment may result in partial/mixed agonist effects that are independent of blockade of T3 binding in some contexts. These properties could ultimately be utilized in drug design and development of new selective TR modulators. PMID:18930112

Thyroid hormones and skeletal muscle — new insights and potential implications

PubMed Central

Salvatore, Domenico; Simonides, Warner S.; Dentice, Monica; Zavacki, Ann Marie; Larsen, P. Reed

2014-01-01

Thyroid hormone signalling regulates crucial biological functions, including energy expenditure, thermogenesis, development and growth. The skeletal muscle is a major target of thyroid hormone signalling. The type two (DIO2) and three (DIO3) iodothyronine deiodinases have been identified in skeletal muscle. DIO2 expression is tightly regulated and catalyzes outer ring monodeiodination of the secreted prohormone tetraiodothyronine (T4) to generate the active hormone triiodothyronine (T3). T3 may remain in the myocyte to signal through nuclear receptors or exit the cell to mix with the extracellular pool. By contrast, DIO3 inactivates T3 through removal of an inner ring iodine. Regulation of the expression and activity of deiodinases constitutes a cell-autonomous, pre-receptor mechanism for controlling the intracellular concentration of T3. This local control of T3 activity is crucial during the various phases of myogenesis. Here, we review the roles of T3 in skeletal muscle development and homeostasis, with a focus on the emerging local deiodinase-mediated control of T3 signalling. Moreover, we discuss these novel findings in the context of both muscle homeostasis and pathology, and examine how they can be therapeutically harnessed to improve satellite cell-mediated muscle repair in patients with skeletal muscle disorders, muscle atrophy or injury. PMID:24322650

Induction and prevention of low-T3 syndrome in exercising women.

PubMed

Loucks, A B; Callister, R

1993-05-01

To investigate the influence of exercise on thyroid metabolism, 46 healthy young regularly menstruating sedentary women were randomly assigned to a 3 x 2 experimental design of aerobic exercise and energy availability treatments. Energy availability was defined as dietary energy intake minus energy expenditure during exercise. After 4 days of treatments, low energy availability (8 vs. 30 kcal.kg body wt-1.day-1) had reduced 3,5,3'-triiodothyronine (T3) by 15% and free T3 (fT3) by 18% and had increased thyroxine (T4) by 7% and reverse T3 (rT3) by 24% (all P < 0.01), whereas free T4 (fT4) was unchanged (P = 0.08). Exercise quantity (0 vs. 1,300 kcal/day) and intensity (40 vs. 70% of aerobic capacity) did not affect any thyroid hormone (all P > 0.10). That is, low-T3 syndrome was induced by the energy cost of exercise and was prevented in exercising women by increasing dietary energy intake. Selective observation of low-T3 syndrome in amenorrheic and not in regularly menstruating athletes suggests that exercise may compromise the availability of energy for reproductive function in humans. If so, athletic amenorrhea might be prevented or reversed through dietary reform without reducing exercise quantity or intensity.

Effects of T3 treatment on brown adipose tissue and energy expenditure in a patient with craniopharyngioma and hypothalamic obesity.

PubMed

van Santen, Hanneke M; Schouten-Meeteren, Antoinette Y; Serlie, Mireille; Meijneke, Ruud W H; van Trotsenburg, A S; Verberne, Hein; Holleman, Frits; Fliers, Eric

2015-01-01

Patients treated for childhood craniopharyngioma often develop hypothalamic obesity (HO), which has a huge impact on the physical condition and quality of life of these patients. Treatment for HO thus far has been disappointing, and although several different strategies have been attempted, all interventions had only transient effects. Since thyroid hormones increase energy expenditure metabolism (thyroid hormone induced thermogenesis), it was speculated that treatment with tri-iodothyronine (T3) may be beneficial. In 2002, a case report was published on reduction of body weight after T3 treatment for HO. No studies have been reported since. Recent experimental studies in rodents showed that T3 increases brown adipose tissue (BAT) activity via (pre)sympathetic pathways between the hypothalamus and BAT. Our aim was to investigate whether T3 treatment increases BAT activity in a patient with HO resulting from (treatment of) childhood craniopharyngioma. Thyroxine treatment for central hypothyroidism was switched to T3 monotherapy. Serum T3 and free thyroxine (FT4) concentrations were measured twice weekly for 2 months. ¹²³I-MIBG and ¹⁸F-FDG-PET after induction of non-shivering thermogenesis for the assessment of sympathetic and metabolic activity of BAT as well as indirect calorimetry for assessment of resting energy expenditure were performed before and during T3 treatment. No change in sympathetic and metabolic BAT activity, energy expenditure, or BMI was seen during T3 treatment despite the expected changes in thyroid hormone plasma concentrations. We conclude that T3 monotherapy does not seem to be effective in decreasing HO in childhood craniopharyngioma.

Thyroid hormones and menstrual cycle function in a longitudinal cohort of premenopausal women.

PubMed

Jacobson, Melanie H; Howards, Penelope P; Darrow, Lyndsey A; Meadows, Juliana W; Kesner, James S; Spencer, Jessica B; Terrell, Metrecia L; Marcus, Michele

2018-05-01

Previous studies have reported that hyperthyroid and hypothyroid women experience menstrual irregularities more often compared with euthyroid women, but reasons for this are not well-understood and studies on thyroid hormones among euthyroid women are lacking. In a prospective cohort study of euthyroid women, this study characterised the relationship between thyroid hormone concentrations and prospectively collected menstrual function outcomes. Between 2004-2014, 86 euthyroid premenopausal women not lactating or taking hormonal medications participated in a study measuring menstrual function. Serum thyroid hormones were measured before the menstrual function study began. Women then collected first morning urine voids and completed daily bleeding diaries every day for three cycles. Urinary oestrogen and progesterone metabolites (estrone 3-glucuronide (E 1 3G) and pregnanediol 3-glucuronide (Pd3G)) and follicle-stimulating hormone were measured and adjusted for creatinine (Cr). Total thyroxine (T 4 ) concentrations were positively associated with Pd3G and E 1 3G. Women with higher (vs lower) T 4 had greater luteal phase maximum Pd3G (Pd3G = 11.7 μg/mg Cr for women with high T 4 vs Pd3G = 9.5 and 8.1 μg/mg Cr for women with medium and low T 4 , respectively) and greater follicular phase maximum E 1 3G (E 1 3G = 41.7 ng/mg Cr for women with high T 4 vs E 1 3G = 34.3 and 33.7 ng/mg Cr for women with medium and low T 4 , respectively). Circulating thyroid hormone concentrations were associated with subtle differences in menstrual cycle function outcomes, particularly sex steroid hormone levels in healthy women. Results contribute to the understanding of the relationship between thyroid function and the menstrual cycle, and may have implications for fertility and chronic disease. © 2018 John Wiley & Sons Ltd.

Insulin sensitivity and its relation to hormones in adolescent boys and girls.

PubMed

Aldhoon-Hainerová, Irena; Zamrazilová, Hana; Hill, Martin; Hainer, Vojtěch

2017-02-01

A subset of obese individuals lacks cardiometabolic impairment. We aimed to analyze hormonal profiles of insulin-sensitive obese (ISO) and insulin-resistant obese (IRO) adolescents and determine hormonal predictors of homeostasis model of insulin resistance (HOMA-IR). A threshold of 3.16 of HOMA-IR was used to classify ISO (<3.16) IRO (≥3.16). In 702 individuals aged 13-18years (55.8% girls) anthropometric and laboratory [blood glucose, insulin, thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), sex hormone-binding globulin (SHBG), steroid hormones, luteinizing hormone, follicle stimulating hormone, prolactin, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like-peptide 1glucagon, leptin, resistin, visfatin, leptin, adiponectin and adipsin] assessments were performed. Orthogonal projections to latent structures and Mann-Whitney tests with Bonferroni correction were applied for statistical analysis. 52.6% girls and 42.9% boys were insulin sensitive. In the predictive model of HOMA-IR thyroid function tests, adiponectin, ghrelin and leptin concentrations played an important role in both genders. Prolactin, testosterone and glucagon contributed to the model only in boys, while progesterone and dehydroepiandrosterone sulfate levels only in girls. After Bonferroni correction levels of leptin, adiponectin, leptin/adiponectin ratio, SHBG and fT4/TSH ratio in both genders, testosterone and glucagon levels in boys and levels of TSH and fT3 in girls were related to insulin sensitivity. Metabolic health defined by HOMA-IR is partly predicted by various hormones. Some of them are gender specific. Free T4/TSH and leptin/adiponectin ratios are related to insulin sensitivity in both genders. Copyright © 2016 Elsevier Inc. All rights reserved.

Low T3 syndrome as a predictor of poor prognosis in chronic lymphocytic leukemia.

PubMed

Gao, Rui; Chen, Rui-Ze; Xia, Yi; Liang, Jin-Hua; Wang, Li; Zhu, Hua-Yuan; Zhu Wu, Jia-; Fan, Lei; Li, Jian-Yong; Yang, Tao; Xu, Wei

2018-02-19

Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels. A propensity score-matched method was performed to balance the baseline characteristics. Multivariate Cox regression analyses screened the independent prognostic factors related to time-to-first-treatment (TTFT) and cancer-specific survival (CSS). Area under the curve (AUC) assessed the predictive accuracy of CLL-International Prognostic Index (IPI) together with low T3 syndrome. The results showed that 37 (14.34%) patients had low T3 syndrome, which was significantly associated with unfavorable TTFT and CSS in the propensity-matched cohort, and it was an independent prognostic indicator for both TTFT and CSS. Serum FT3 level was positively related to protein metabolism and anemia, and inversely related to inflammatory state. Patients with only low FT3 demonstrated better survival than those with synchronously low FT3 and FT4, while those with synchronously low FT3, FT4 and TSH had the worst clinical outcome. Low T3 syndrome together with CLL-IPI had larger AUCs compared with CLL-IPI alone in TTFT and CSS prediction. In conclusion, low T3 syndrome may be a good candidate for predicting prognosis in future clinical practice of CLL. © 2018 UICC.

Thyroid hormone deiodinases D1, D2, and D3 are expressed in human endothelial dermal microvascular line: effects of thyroid hormones.

PubMed

Sabatino, Laura; Lubrano, Valter; Balzan, Silvana; Kusmic, Claudia; Del Turco, Serena; Iervasi, Giorgio

2015-01-01

Endothelial system acts as a large endocrine organ in the human body; however, little is still known about the regulative role of THs on endothelial cells. Aim of the present study was to investigate the expression of the TH deiodinases (D1, D2, and D3) and TH receptors (TRα1, TRα2, and TRβ1) in an endothelial microvascular cultured cell model (HMEC-1), after stimulation with triiodothyronine (T3, 10-100 nM), thyroxine (T4, 10-100 nM), and reverse T3 (rT3, 1-10 nM). DIO1 was significantly inhibited by T4 at 10 and 100 nM (p < 0.001). rT3 significantly inhibited DIO1 at 1 nM concentration (p < 0.01) and stimulated DIO1 at 10 nM dosage (p < 0.001). T4 and rT3 significantly inhibited DIO2 at all concentrations. DIO3 was induced at 100 nM T3 (p < 0.05) and 100 nM rT3 (p < 0.01), and TRα1 and TRα2 mRNAs were significantly increased after 100 nM T3 treatment (p < 0.05) and decreased after 1 and 10 nM rT3 (p < 0.05). TRβ1 was significantly increased by all THs at different concentrations: 10 nM T3 and 100 nM T3 (p < 0.05), 1 nM rT3 (p < 0.001), and 100 nM T4 (p < 0.01). D1 and D2 protein levels were evaluated, but no significant difference was observed for any hormonal treatment. For the first time, we found that the TH deiodinases and receptors are expressed in endothelial HMEC-1 cells. These findings might be of significant clinical relevance, given the important regulatory role of the endothelium as first barrier to the bloodstream.

The Mechanism of the Calorigenic Action of Thyroid Hormone

PubMed Central

Ismail-Beigi, Faramarz; Edelman, Isidore S.

1971-01-01

In an earlier study, we proposed that thyroid hormone stimulation of energy utilization by the Na+ pump mediates the calorigenic response. In this study, the effects of triiodothyronine (T3) on total oxygen consumption (Q OO2), the ouabain-sensitive oxygen consumption [Q OO2(t)], and NaK-ATPase in liver, kidney, and cerebrum were measured. In liver, ∼90% of the increase in Q OO2 produced by T3 in either thyroidectomized or euthyroid rats was attributable to the increase in Q OO2(t). In kidney, the increase in Q OO2(t) accounted for 29% of the increase in Q OO2 in thyroidectomized and 46% of the increase in Q OO2 in euthyroid rats. There was no demonstrable effect of T3 in euthyroid rats on Q OO2 or Q OO2(t) of cerebral slices. The effects of T3 on NaK-ATPase activity in homogenates were as follows: In liver +81% from euthyroid rats and +54% from hypothyroid rats. In kidney, +21% from euthyroid rats and +69% from hypothyroid rats. T3 in euthyroid rats produced no significant changes in NaK-ATPase or Mg-ATPase activity of cerebral homogenates. Liver plasma membrane fractions showed a 69% increase in NaK-ATPase and no significant changes in either Mg-ATPase or 5'-nucleotidase activities after T3 injection. These results indicate that thyroid hormones stimulate NaK-ATPase activity differentially. This effect may account, at least in part, for the calorigenic effects of these hormones. PMID:4252666

Thyroid hormone concentrations, disease, physical function, and mortality in elderly men.

PubMed

van den Beld, Annewieke W; Visser, Theo J; Feelders, Richard A; Grobbee, Diederick E; Lamberts, Steven W J

2005-12-01

Physiological changes in thyroid hormone concentrations might be related to changes in the overall physical function in the elderly. We determined to what extent thyroid hormone concentrations are related to physical function and mortality in elderly men. A longitudinal population study (the Zoetermeer study) was conducted. Mortality was registered in the subsequent 4 yr. Four hundred three independently and ambulatory living men (aged 73-94 yr) participated. The study examined the association between serum thyroid hormones and parameters of physical function as well as the association with mortality. TSH, free T4 (FT4) total T4, T3, rT3, and T4-binding globulin were measured. Physical function was estimated by the number of problems in activities of daily living, a measure of physical performance score (PPS), leg extensor strength and grip strength, bone density, and body composition. Serum rT3 increased significantly with age and the presence of disease. Sixty-three men met the biochemical criteria for the low T3 syndrome (decreased serum T3 and increased serum rT3). This was associated with a lower PPS, independent of disease. Furthermore, higher serum FT4 (within the normal range of healthy adults) and rT3 (above the normal range of healthy adults) were related with a lower grip strength and PPS, independent of age and disease. Isolated low T3 was associated with a better PPS and a higher lean body mass. Low FT4 was related to a decreased risk of 4-yr mortality. In a population of independently living elderly men, higher FT4 and rT3 concentrations are associated with a lower physical function. High serum rT3 may result from a decreased peripheral metabolism of thyroid hormones due to the aging process itself and/or disease and may reflect a catabolic state. Low serum FT4 is associated with a better 4-yr survival; this may reflect an adaptive mechanism to prevent excessive catabolism.

Evidence of the Presence of Thyroid Hormones in Achatina fulica Snails.

PubMed

Lustrino, Danilo; Silva, Alba C M; Araujo, Iracema G; Tunholi, Victor M; Tunholi-Alves, Vinícius M; Castro, Rosane N; Carvalho, Denise P; Pinheiro, Jairo; Marassi, Michelle P

2017-01-01

The objective of this study was to identify thyroid hormones and to examine their putative site of synthesis in Achatina fulica snails. For this purpose, radioimmunoassays were performed for T3 and T4 before and after long starvation with or without hemolymph deproteinization. Sodium/iodide symporter activity in vivo was analyzed through 125I administration with and without KClO4 pretreatment. Only T4 was detected, and its concentration decreased due to starvation or deproteinization. However, high-performance liquid chromatography analysis also showed the presence of T2 and T3 apart from T4, but rT3 was not detected in the A. fulica hemolymph. The sodium/iodide symporter activity was greater in cerebral ganglia than digestive gland, but KClO4 treatment did not inhibit iodide uptake in any of the tissues analyzed. Altogether, our data confirm for the first time the presence of thyroid hormones in A. fulica snails and suggest their participation in the metabolism control in this species, although the putative site of hormone biosynthesis remains to be elucidated.

Hormonal regulation of aquaporin 3: opposing actions of prolactin and cortisol in tilapia gill.

PubMed

Breves, Jason P; Inokuchi, Mayu; Yamaguchi, Yoko; Seale, Andre P; Hunt, Bethany L; Watanabe, Soichi; Lerner, Darren T; Kaneko, Toyoji; Grau, E Gordon

2016-09-01

Aquaporins (Aqps) are expressed within key osmoregulatory tissues where they mediate the movement of water and selected solutes across cell membranes. We leveraged the functional plasticity of Mozambique tilapia (Oreochromis mossambicus) gill epithelium to examine how Aqp3, an aquaglyceroporin, is regulated in response to osmoregulatory demands. Particular attention was paid to the actions of critical osmoregulatory hormones, namely, prolactin (Prl), growth hormone and cortisol. Branchial aqp3 mRNA levels were modulated following changes in environmental salinity, with enhanced aqp3 mRNA expression upon transfer from seawater to freshwater (FW). Accordingly, extensive Aqp3 immunoreactivity was localized to cell membranes of branchial epithelium in FW-acclimated animals. Upon transferring hypophysectomized tilapia to FW, we identified that a pituitary factor(s) is required for Aqp3 expression in FW. Replacement with ovine Prl (oPrl) was sufficient to stimulate Aqp3 expression in hypophysectomized animals held in FW, an effect blocked by coinjection with cortisol. Both oPrl and native tilapia Prls (tPrl177 and tPrl188) stimulated aqp3 in incubated gill filaments in a concentration-related manner. Consistent with in vivo responses, coincubation with cortisol blocked oPrl-stimulated aqp3 expression in vitro Our data indicate that Prl and cortisol act directly upon branchial epithelium to regulate Aqp3 in tilapia. Thus, within the context of the diverse actions of Prl on hydromineral balance in vertebrates, we define a new role for Prl as a regulator of Aqp expression. © 2016 Society for Endocrinology.

Thyroid, cortisol and growth hormone levels in adult Nigerians with metabolic syndrome.

PubMed

Udenze, Ifeoma Christiana; Olowoselu, Olusola Festus; Egbuagha, Ephraim Uchenna; Oshodi, Temitope Adewunmi

2017-01-01

The similarities in presentation of cortisol excess, growth hormone deficiency, hypothyroidism and metabolic syndrome suggest that subtle abnormalities of these endocrine hormones may play a causal role in the development of metabolic syndrome. The aim of this study is to determine the levels of cortisol, thyroid and growth hormones in adult Nigerians with metabolic syndrome and determine the relationship between levels of these hormones and components of the syndrome. This was a case control study conducted at the Lagos University Teaching Hospital, Lagos, Nigeria. Participants were fifty adult men and women with the metabolic syndrome, and fifty, age and sex matched males and females without the metabolic syndrome. Metabolic syndrome was defined based on the NCEP-ATPIII criteria. Written Informed consent was obtained from the participants. Socio demographic and clinical data were collected using a structured questionnaire. Venous blood was collected after an over-night fast. The Ethics committee of the Lagos University Teaching Hospital, Lagos, Nigeria, approved the study protocol. Comparison of continuous variables was done using the Student's t test. Correlation analysis was employed to determine the associations between variables. Statistical significance was set at P<0.05. Triiodotyronine (T3) was significantly decreased (p<0.001) and thyroxine (T4 ) significantly increased ( p<0.001) in metabolic syndrome compared to healthy controls. T3 correlated positively and significantly with waist circumference (p=0.004), glucose (p= 0.002), total cholesterol ( p=0.001) and LDL- cholesterol ( p<0.001 ) and negatively with body mass index ( p<0.001 )and triglyceride ( p=0.026). T4 had a negative significant correlation with waist circumference (p=0.004). Cortisol and growth hormone levels were similar in metabolic syndrome and controls. Cortisol however had a positive significant correlation with waist/hip ratio (p<0.001) while growth hormone correlated positively with

E3 ubiquitin ligases: key regulators of hormone signaling in plants.

PubMed

Kelley, Dior

2018-03-07

Ubiquitin-mediated control of protein stability is central to most aspects of plant hormone signaling. Attachment of ubiquitin to target proteins occurs via an enzymatic cascade with the final step being catalyzed by a family of enzymes known as E3 ubiquitin ligases, which have been classified based on their protein domains and structures. While E3 ubiquitin ligases are conserved among eukaryotes, in plants they are well-known to fulfill unique roles as central regulators of phytohormone signaling, including hormone perception and regulation of hormone biosynthesis. This review will highlight up-to-date findings that have refined well-known E3 ligase-substrate interactions and defined novel E3 ligase substrates that mediate numerous hormone signaling pathways. Additionally, examples of how particular E3 ligases may mediate hormone crosstalk will be discussed as an emerging theme. Looking forward, promising experimental approaches and methods that will provide deeper mechanistic insight into the roles of E3 ubiquitin ligases in plants will be considered. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

An ABI3-interactor of conifers responds to multiple hormones.

PubMed

Zeng, Ying; Zhao, Tiehan; Kermode, Allison

2013-11-01

CnAIP2 (Callitropsis nootkatensis ABI3-Interacting Protein 2) was previously identified as a protein that interacts with the yellow-cedar ABI3 protein. CnAIP2 plays important roles during several key transitions of the plant lifecycle and acts as a global regulator with functions opposite to those of ABI3 proteins. Here we report that the CnAIP2 gene promoter is strongly upregulated by all of the major plant hormones. Young Arabidopsis seedlings expressing a chimeric CnAIP2pro-GUS construct were subjected to exogenously applied hormones; the maximum fold-enhancement of GUS activity was as high as 47-fold, and each hormone showed a distinctive cell/tissue-specific pattern of GUS induction. By far the greatest response was elicited by the synthetic auxin 2,4-D (47-fold induction); the other hormones tested stimulated GUS activities by 8- to 21-fold. The CnAIP2 promoter also responded to glucose and salt (NaCl), albeit to a lesser extent (2- to 3-fold induction). As well as acting in an antagonistic way to the global regulator ABI3, CnAIP2 appears to participate in multiple hormonal crosstalk pathways to carry out its functions.

Physiologic implications of inter-hormonal interference in fish: lessons from the interaction of adrenaline with cortisol and thyroid hormones in climbing perch (Anabas testudineus Bloch).

PubMed

George, Nimta; Peter, Valsa S; Peter, M C Subhash

2013-01-15

Adrenaline and cortisol, the major stress hormones, are known for its direct control on stress response in fish. Likewise, as an important stress modifier hormone, thyroid hormone has also been implicated in stress response of fish. We tested whether the hypothesis on the phenomenon of inter-hormonal interference, a process that explains the hormonal interactions, operates in fish particularly between adrenaline, cortisol and thyroid hormones. To achieve this goal, indices of acid-base, osmotic and metabolic regulations were quantified after adrenaline challenge in propranolol pre-treated air-breathing fish (Anabas testudineus). Short-term adrenaline (10 ng g(-1)) injection for 30 min produced a rise in plasma cortisol without affecting plasma T(3) and T(4). On the contrary, blocking of adrenaline action with a non-selective blocker, propranolol (25 ng g(-1)) for 90 min reduced plasma cortisol along with plasma T(4) and that indicate a possible interference of these hormones in the absence of adrenaline challenge. Similarly, a reduction in plasma T(3) was found after adrenaline challenge in propranolol pre-treated fish and that suggests a functional synergistic interference of adrenaline with T(3). Adrenaline challenge in these fish, however, failed to abolish this propranolol effect. The remarkable systemic hypercapnia and acidosis by propranolol pre-treatment were reversed by adrenaline challenge, pointing to a direct action of adrenaline on acid-base indices probably by a mechanism which may not require β-adrenergic receptor systems. Interestingly, the prominent adrenaline-induced hyperglycemia, hyperlactemia and hyperuremea were not altered by propranolol treatment. Similarly, adrenaline challenge promoted and propranolol reduced the osmotic competencies of the gills, kidneys and liver of this fish as evident in the sodium and proton pump activities. The modified physiologic actions of adrenaline and its modified interaction with THs and cortisol in blocked

Changes of thyroid hormone levels and related gene expression in zebrafish on early life stage exposure to triadimefon.

PubMed

Liu, Shaoying; Chang, Juhua; Zhao, Ying; Zhu, Guonian

2011-11-01

In this study, zebrafish was exposed to triadimefon. Thyroid hormones levels and the expression of related genes in the hypothalamic-pituitary-thyroid (HPT) axis, including thyroid-stimulating hormone (TSH-beta), deiodinases (dio1 and dio2) and the thyroid hormone receptor (thraa and thrb) were evaluated. After triadimefon exposure, increased T4 can be explained by increased thyroid-stimulating hormone (TSH-beta). The conversion of T4 to T3 (deiodinase type I-dio1) was decreased, which reduced the T3 level. Thyroid hormone receptor beta (thrb) mRNA levels were significantly down-regulated, possibly as a response to the decreased T3 levels. The overall results indicated that triadimefon exposure could alter gene expression in the HPT axis and that mechanisms of disruption of thyroid status by triadimefon could occur at several steps in the synthesis, regulation, and action of thyroid hormones. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Thyroid Hormone Economy in the Perinatal Mouse Brain: Implications for Cerebral Cortex Development.

PubMed

Bárez-López, Soledad; Obregon, Maria Jesus; Bernal, Juan; Guadaño-Ferraz, Ana

2018-05-01

Thyroid hormones (THs, T4 and the transcriptionally active hormone T3) play an essential role in neurodevelopment; however, the mechanisms underlying T3 brain delivery during mice fetal development are not well known. This work has explored the sources of brain T3 during mice fetal development using biochemical, anatomical, and molecular approaches. The findings revealed that during late gestation, a large amount of fetal brain T4 is of maternal origin. Also, in the developing mouse brain, fetal T3 content is regulated through the conversion of T4 into T3 by type-2 deiodinase (D2) activity, which is present from earlier prenatal stages. Additionally, D2 activity was found to be essential to mediate expression of T3-dependent genes in the cerebral cortex, and also necessary to generate the transient cerebral cortex hyperthyroidism present in mice lacking the TH transporter Monocarboxylate transporter 8. Notably, the gene encoding for D2 (Dio2) was mainly expressed at the blood-cerebrospinal fluid barrier (BCSFB). Overall, these data signify that T4 deiodinated by D2 may be the only source of T3 during neocortical development. We therefore propose that D2 activity at the BCSFB converts the T4 transported across the choroid plexus into T3, thus supplying the brain with active hormone to maintain TH homeostasis.

Ghrelin inhibits the apoptosis of MC3T3-E1 cells through ERK and AKT signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, Qiu-Hua; Liu, Yuan; Wu, Shan-Shan

Ghrelin is a 28-amino-acid peptide that acts as a natural endogenous ligand of the growth hormone secretagogue receptor (GHSR) and strongly stimulates the release of growth hormone from the hypothalamus–pituitary axis. Previous studies have identified the important physiological effects of ghrelin on bone metabolism, such as regulating proliferation and differentiation of osteoblasts, independent of GH/IGF-1 axis. However, research on effects and mechanisms of ghrelin on osteoblast apoptosis is still rare. In this study, we identified expression of GHSR in MC3T3-E1 cells and determined the effects of ghrelin on the apoptosis of osteoblastic MC3T3-E1 cells and the mechanism involved. Our datamore » demonstrated that ghrelin inhibited the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, as determined by terminal deoxynucleotidyl transferase-mediated deoxyribonucleotide triphosphate nick end-labeling (TUNEL) and ELISA assays. Moreover, ghrelin upregulated Bcl-2 expression and downregulated Bax expression in a dose-dependent manner. Our study also showed decreased activated caspase-3 activity under the treatment of ghrelin. Further study suggested that ghrelin stimulated the phosphorylation of ERK and AKT. Pretreatment of cells with the ERK inhibitor PD98059, PI3K inhibitor LY294002, and GHSR-siRNA blocked the ghrelin-induced activation of ERK and AKT, respectively; however, ghrelin did not stimulate the phosphorylation of p38 or JNK. PD90859, LY294002 and GHSR-siRNA attenuated the anti-apoptosis effect of ghrelin in MC3T3-E1 cells. In conclusion, ghrelin inhibits the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, which may be mediated by activating the GHSR/ERK and GHSR/PI3K/AKT signaling pathways. - Highlights: • We explored the effects of ghrelin on serum deprivation-induced MC3T3-E1 cells apoptosis. • Both ELISA and TUNEL were used to detect the apoptosis. • The receptor of ghrelin, GHSR, was expressed in MC3T

Gene expression analysis and microdialysis suggest hypothalamic triiodothyronine (T3) gates daily torpor in Djungarian hamsters (Phodopus sungorus).

PubMed

Bank, Jonathan H H; Cubuk, Ceyda; Wilson, Dana; Rijntjes, Eddy; Kemmling, Julia; Markovsky, Hanna; Barrett, Perry; Herwig, Annika

2017-07-01

Thyroid hormones play an important role in regulating seasonal adaptations of mammals. Several studies suggested that reduced availability of 3,3',5-triiodothyronine (T3) in the hypothalamus is required for the physiological adaptation to winter in Djungarian hamsters. We have previously shown that T3 is involved in the regulation of daily torpor, but it remains unclear, whether T3 affects torpor by central or peripheral mechanisms. To determine the effect of T3 concentrations within the hypothalamus in regulating daily torpor, we tested the hypothesis that low hypothalamic T3 metabolism would favour torpor and high T3 concentrations would not. In experiment 1 gene expression in torpid hamsters was assessed for transporters carrying thyroid hormones between cerebrospinal fluid and hypothalamic cells and for deiodinases enzymes, activating or inactivating T3 within hypothalamic cells. Gene expression analysis suggests reduced T3 in hypothalamic cells during torpor. In experiment 2, hypothalamic T3 concentrations were altered via microdialysis and torpor behaviour was continuously monitored by implanted body temperature transmitters. Increased T3 concentrations in the hypothalamus reduced expression of torpor as well as torpor bout duration and depth. Subsequent analysis of gene expression in the ependymal layer of the third ventricle showed clear up-regulation of T3 inactivating deiodinase 3 but no changes in several other genes related to photoperiodic adaptations in hamsters. Finally, serum analysis revealed that increased total T3 serum concentrations were not necessary to inhibit torpor expression. Taken together, our results are consistent with the hypothesis that T3 availability within the hypothalamus significantly contributes to the regulation of daily torpor via a central pathway.

Sex-hormone-binding globulin.

PubMed

Anderson, D C

1974-01-01

A review was made to understand how plasma binding protein might influence sex-hormone action in target tissues. Steroids are predominately bound to plasma proteins and only unbound steroids enter the cells. Sex-hormone-binding globulin (SHBG) binds to both the main circulating steroid T and E2 but changes in SHBG concentrations exert significant results. Increased SHBG levels increase estrogen production and decreases T activity; whereas, increased androgens increase T action and inhibit SHBG production. These disturbances in hormone maintenance may lead to abnormal adult sex differentiation such as hirsutism and forms of hynaecomastia. By developing SHBG concentration measurement methods-responses of hirsutism to glucocorticoid or estrogem may be assessed. In addition, the effect of thyroid hormones on SHBG may also have therapeutic implications in endocrine disease.

Thyroid hormone concentrations in captive and free-ranging West Indian manatees (Trichechus manatus).

PubMed

Ortiz, R M; MacKenzie, D S; Worthy, G A

2000-12-01

Because thyroid hormones play a critical role in the regulation of metabolism, the low metabolic rates reported for manatees suggest that thyroid hormone concentrations in these animals may also be reduced. However, thyroid hormone concentrations have yet to be examined in manatees. The effects of captivity, diet and water salinity on plasma total triiodothyronine (tT(3)), total thyroxine (tT(4)) and free thyroxine (fT(4)) concentrations were assessed in adult West Indian manatees (Trichechus manatus). Free-ranging manatees exhibited significantly greater tT(4) and fT(4) concentrations than captive adults, regardless of diet, indicating that some aspect of a captive existence results in reduced T(4) concentrations. To determine whether this reduction might be related to feeding, captive adults fed on a mixed vegetable diet were switched to a strictly sea grass diet, resulting in decreased food consumption and a decrease in body mass. However, tT(4) and fT(4) concentrations were significantly elevated over initial values for 19 days. This may indicate that during periods of reduced food consumption manatees activate thyroid-hormone-promoted lipolysis to meet water and energetic requirements. Alterations in water salinity for captive animals did not induce significant changes in thyroid hormone concentrations. In spite of lower metabolic rates, thyroid hormone concentrations in captive manatees were comparable with those for other terrestrial and marine mammals, suggesting that the low metabolic rate in manatees is not attributable to reduced circulating thyroid hormone concentrations.

Effects of acute microinjections of the thyroid hormone derivative 3-iodothyronamine to the preoptic region of adult male rats on sleep, thermoregulation and motor activity

PubMed Central

James, Thomas D.; Moffett, Steven X.; Scanlan, Thomas S.; Martin, Joseph V.

2014-01-01

The decarboxylated thyroid hormone derivative 3-iodothyronamine (T1AM) has been reported as having behavioral and physiological consequences distinct from those of thyroid hormones. Here, we investigate the effects of T1AM on EEG-defined sleep after acute administration to the preoptic region of adult male rats. Our laboratory recently demonstrated a decrease in EEG-defined sleep after administration of 3,3′,5-triiodo-L-thyronine (T3) to the same brain region. After injection of T1AM or vehicle solution, EEG, EMG, activity, and core body temperature were recorded for 24 h. Sleep parameters were determined from EEG and EMG data. Earlier investigations found contrasting systemic effects of T3 and T1AM, such as decreased heart rate and body temperature after intraperitoneal T1AM injection. However, nREM sleep was decreased in the present study after injections of 1 or 3 μg T1AM, but not after 0.3 or 10 μg, closely mimicking the previously reported effects of T3 administration to the preoptic region. The biphasic dose–response observed after either T1AM or T3 administration seems to indicate shared mechanisms and/or functions of sleep regulation in the preoptic region. Consistent with systemic administration of T1AM, however, microinjection of T1AM decreased body temperature. The current study is the first to show modulation of sleep by T1AM, and suggests that T1AM and T3 have both shared and independent effects in the adult mammalian brain. PMID:23702093

Prognostic Value of Thyroid Hormone Levels in Patients Evaluated for Liver Transplantation

PubMed Central

Van Thiel, David H.; Udani, Mahendra; Schade, Robert R.; Sanghvi, Agit; Starzl, Thomas E.

2010-01-01

The thyroid hormones T4, T3, rT3 and TSH were assayed in 134 adult patients evaluated and accepted as potential liver transplant candidates at the University of Pittsburgh from March, 1981 to December, 1983. The subsequent course of these patients was evaluated with respect to the levels of these hormones obtained at the time of acceptance for transplantation. T4 levels were increased significantly while their T3 levels were reduced (both p < 0.01) in those who survived and were discharged home as compared to either those who died waiting to be transplanted or died following the procedure. As a result, the ratio of T3/T4 was reduced markedly (p < 0.01) in those who were transplanted and survived as compared to those not transplanted or dying following transplantation. Importantly, the rT3 levels clearly separated (p < 0.01) those who would die prior to transplantation from those who would survive to be transplanted. Finally, the ratio rT3/T3 even more clearly separates those who will die prior to transplantation (p < 0.01) from the other two groups. These data suggest that thyroid hormone levels, particularly rT3 levels, might be useful in setting priorities for which patients referred for a transplantation evaluation should be accepted into the program and in determining who among accepted patients should be operated upon in preference to others also accepted and waiting to be transplanted. PMID:2993148

Maternal exposure to UV filters: associations with maternal thyroid hormones, IGF-I/IGFBP3 and birth outcomes.

PubMed

Krause, M; Frederiksen, H; Sundberg, K; Jørgensen, F S; Jensen, L N; Nørgaard, P; Jørgensen, C; Ertberg, P; Petersen, J H; Feldt-Rasmussen, U; Juul, A; Drzewiecki, K T; Skakkebaek, N E; Andersson, A M

2018-02-01

Several chemical UV filters/absorbers ('UV filters' hereafter) have endocrine-disrupting properties in vitro and in vivo . Exposure to these chemicals, especially during prenatal development, is of concern. To examine maternal exposure to UV filters, associations with maternal thyroid hormone, with growth factor concentrations as well as to birth outcomes. Prospective study of 183 pregnant women with 2nd trimester serum and urine samples available. Maternal concentrations of the chemical UV filters benzophenone-1 (BP-1) and benzophenone-3 (BP-3) in urine and 4-hydroxy-benzophenone (4-HBP) in serum were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relationships between 2nd trimester maternal concentrations of the three chemical UV filters and maternal serum concentrations of thyroid hormones and growth factors, as well as birth outcomes (weight, height, and head and abdominal circumferences) were examined. Positive associations between maternal serum concentrations of 4-HBP and triiodothyronine (T 3 ), thyroxine (T 4 ), insulin-like growth factor I (IGF-I) and its binding protein IGFBP3 were observed in mothers carrying male fetuses. Male infants of mothers in the middle 4-HBP exposure group had statistically significantly lower weight and shorter head and abdominal circumferences at birth compared to the low exposure group. Widespread exposure of pregnant women to chemical UV filters and the possible impact on maternal thyroid hormones and growth factors, and on fetal growth, calls for further studies on possible long-term consequences of the exposure to UV filters on fetal development and children's health. © 2018 The authors.

Sex Differences in Brain Thyroid Hormone Levels during Early Post-Hatching Development in Zebra Finch (Taeniopygia guttata).

PubMed

Yamaguchi, Shinji; Hayase, Shin; Aoki, Naoya; Takehara, Akihiko; Ishigohoka, Jun; Matsushima, Toshiya; Wada, Kazuhiro; Homma, Koichi J

2017-01-01

Thyroid hormones are closely linked to the hatching process in precocial birds. Previously, we showed that thyroid hormones in brain had a strong impact on filial imprinting, an early learning behavior in newly hatched chicks; brain 3,5,3'-triiodothyronine (T3) peaks around hatching and imprinting training induces additional T3 release, thus, extending the sensitive period for imprinting and enabling subsequent other learning. On the other hand, blood thyroid hormone levels have been reported to increase gradually after hatching in altricial species, but it remains unknown how the brain thyroid hormone levels change during post-hatching development of altricial birds. Here, we determined the changes in serum and brain thyroid hormone levels of a passerine songbird species, the zebra finch using radioimmunoassay. In the serum, we found a gradual increase in thyroid hormone levels during post-hatching development, as well as differences between male and female finches. In the brain, there was clear surge in the hormone levels during development in males and females coinciding with the time of fledging, but the onset of the surge of thyroxine (T4) in males preceded that of females, whereas the onset of the surge of T3 in males succeeded that of females. These findings provide a basis for understanding the functions of thyroid hormones during early development and learning in altricial birds.

A thyroid hormone receptor mutation that dissociates thyroid hormone regulation of gene expression in vivo

PubMed Central

Machado, Danielle S.; Sabet, Amin; Santiago, Leticia A.; Sidhaye, Aniket R.; Chiamolera, Maria I.; Ortiga-Carvalho, Tania M.; Wondisford, Fredric E.

2009-01-01

Resistance to thyroid hormone (RTH) is most often due to point mutations in the β-isoform of the thyroid hormone (TH) receptor (TR-β). The majority of mutations involve the ligand-binding domain, where they block TH binding and receptor function on both stimulatory and inhibitory TH response elements. In contrast, a few mutations in the ligand-binding domain are reported to maintain TH binding and yet cause RTH in certain tissues. We introduced one such naturally occurring human RTH mutation (R429Q) into the germline of mice at the TR-β locus. R429Q knock-in (KI) mice demonstrated elevated serum TH and inappropriately normal thyroid-stimulating hormone (TSH) levels, consistent with hypothalamic–pituitary RTH. In contrast, 3 hepatic genes positively regulated by TH (Dio1, Gpd1, and Thrsp) were increased in R429Q KI animals. Mice were then rendered hypothyroid, followed by graded T3 replacement. Hypothyroid R429Q KI mice displayed elevated TSH subunit mRNA levels, and T3 treatment failed to normally suppress these levels. T3 treatment, however, stimulated pituitary Gh levels to a greater degree in R429Q KI than in control mice. Gsta, a hepatic gene negatively regulated by TH, was not suppressed in R429Q KI mice after T3 treatment, but hepatic Dio1 and Thrsp mRNA levels increased in response to TH. Cardiac myosin heavy chain isoform gene expression also showed a specific defect in TH inhibition. In summary, the R429Q mutation is associated with selective impairment of TH-mediated gene repression, suggesting that the affected domain, necessary for TR homodimerization and corepressor binding, has a critical role in negative gene regulation by TH. PMID:19439650

Thyroid hormone stimulates progesterone release from human luteal cells by generating a proteinaceous factor.

PubMed

Datta, M; Roy, P; Banerjee, J; Bhattacharya, S

1998-09-01

Blood samples collected from 29 women (aged between 19 and 35 years) during the luteal phase of the menstrual cycle (between days 18 and 23 of the cycle) showed that deficiency in thyroid hormone level is related to a decrease in progesterone (P4) secretion. To observe the effect of thyroid hormone on human ovarian luteal cells, 3,5,3'-triiodothyronine (T3; 125 ng/ml) was added to luteal cells in vitro. T3 significantly stimulated progesterone release (P < 0.01) from luteal cells and this could be blocked by cycloheximide, indicating a protein mediator for the T3 effect. The T3 stimulatory effect was inhibited by anti-T3 antibody suggesting specificity of T3 action. Addition of T3 caused a more than threefold increase in cellular protein synthesis which was inhibited by cycloheximide. Preparation of partially purified thyroid hormone-induced factor (TIF) (from peak II of Sephadex G 100 chromatography of T3-incubated cells), and its addition to luteal cell incubations caused a significant increase in P4 release (P < 0.05). Incubation with trypsin or treatment with heat destroyed the stimulatory effect of TIF on P4 release, indicating the proteinaceous nature of TIF. Purified thyroid hormone-induced protein. (TIP) from rat granulosa cells and fish ovarian follicles greatly stimulated P4 release from human luteal cells. These results suggest that T3 stimulation of P4 release from human luteal cells is not direct, but is mediated through a putative protein factor, which appears to be a protein conserved through evolution as far as its biological activity is concerned.

Role of Thyroid Hormones in Skeletal Development and Bone Maintenance

PubMed Central

Bassett, J. H. Duncan

2016-01-01

The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art. PMID:26862888

OsSUV3 transgenic rice maintains higher endogenous levels of plant hormones that mitigates adverse effects of salinity and sustains crop productivity.

PubMed

Sahoo, Ranjan Kumar; Ansari, Mohammad Wahid; Tuteja, Renu; Tuteja, Narendra

2014-01-01

The SUV3 (suppressor of Var 3) gene encodes a DNA and RNA helicase, which is localized in the mitochondria. Plant SUV3 has not yet been characterized in detail. However, the Arabidopsis ortholog of SUV3 (AT4G14790) has been shown to be involved in embryo sac development. Previously, we have reported that rice SUV3 functions as DNA and RNA helicase and provides salinity stress tolerance by maintaining photosynthesis and antioxidant machinery. Here, we report further analysis of the transgenic OsSUV3 rice plants under salt stress. The transgenic OsSUV3 overexpressing rice T1 lines showed significantly higher endogenous content of plant hormones viz., gibberellic acid (GA3), zeatin (Z) and indole-3-acetic acid (IAA) in leaf, stem and root as compared to wild-type (WT), vector control (VC) and antisense (AS) plants under salt (200 mM NaCl) stress condition. A similar trend of endogenous plant hormones profile was also reflected in the T2 generation of OsSUV3 transgenic rice under defined parameters and stress condition. In response to stress, OsSUV3 rice plants maintained plant hormone levels that regulate the expression of several stress-induced genes and reduce adverse effects of salt on plant growth and development and therefore sustains crop productivity.

Action of specific thyroid hormone receptor α(1) and β(1) antagonists in the central and peripheral regulation of thyroid hormone metabolism in the rat.

PubMed

van Beeren, Hermina C; Kwakkel, Joan; Ackermans, Mariëtte T; Wiersinga, Wilmar M; Fliers, Eric; Boelen, Anita

2012-12-01

The iodine-containing drug amiodarone (Amio) and its noniodine containing analogue dronedarone (Dron) are potent antiarrhythmic drugs. Previous in vivo and in vitro studies have shown that the major metabolite of Amio, desethylamiodarone, acts as a thyroid hormone receptor (TR) α(1) and β(1) antagonist, whereas the major metabolite of Dron debutyldronedarone acts as a selective TRα(1) antagonist. In the present study, Amio and Dron were used as tools to discriminate between TRα(1) or TRβ(1) regulated genes in central and peripheral thyroid hormone metabolism. Three groups of male rats received either Amio, Dron, or vehicle by daily intragastric administration for 2 weeks. We assessed the effects of treatment on triiodothyronine (T(3)) and thyroxine (T(4)) plasma and tissue concentrations, deiodinase type 1, 2, and 3 mRNA expressions and activities, and thyroid hormone transporters monocarboxylate transporter 8 (MCT8), monocarboxylate transporter 10 (MCT10), and organic anion transporter 1C1 (OATP1C1). Amio treatment decreased serum T(3), while serum T(4) and thyrotropin (TSH) increased compared to Dron-treated and control rats. At the central level of the hypothalamus-pituitary-thyroid axis, Amio treatment decreased hypothalamic thyrotropin releasing hormone (TRH) expression, while increasing pituitary TSHβ and MCT10 mRNA expression. Amio decreased the pituitary D2 activity. By contrast, Dron treatment resulted in decreased hypothalamic TRH mRNA expression only. Upon Amio treatment, liver T(3) concentration decreased substantially compared to Dron and control rats (50%, p<0.01), but liver T(4) concentration was unaffected. In addition, liver D1, mRNA, and activity decreased, while the D3 activity and mRNA increased. Liver MCT8, MCT10, and OATP1C1 mRNA expression were similar between groups. Our results suggest an important role for TRα1 in the regulation of hypothalamic TRH mRNA expression, whereas TRβ plays a dominant role in pituitary and liver thyroid

Direct regulation of androgen receptor-associated protein 70 by thyroid hormone and its receptors.

PubMed

Tai, Pei-Ju; Huang, Ya-Hui; Shih, Chung-Hsuan; Chen, Ruey-Nan; Chen, Chi-De; Chen, Wei-Jan; Wang, Chia-Siu; Lin, Kwang-Huei

2007-07-01

Thyroid hormone (T3) regulates multiple physiological processes during development, growth, differentiation, and metabolism. Most T3 actions are mediated via thyroid hormone receptors (TRs) that are members of the nuclear hormone receptor superfamily of ligand-dependent transcription factors. The effects of T3 treatment on target gene regulation was previously examined in TRalpha1-overexpressing hepatoma cell lines (HepG2-TRalpha1). Androgen receptor (AR)-associated protein 70 (ARA70) was one gene found to be up-regulated by T3. The ARA70 is a ligand-dependent coactivator for the AR and was significantly increased by 4- to 5-fold after T3 treatment by Northern blot analyses in the HepG2-TRalpha1 stable cell line. T3 induced a 1- to 2-fold increase in the HepG2-TRbeta1 stable cell line. Both stable cell lines attained the highest fold expression after 24 h treatment with 10 nM T3. The ARA70 protein was increased up to 1.9-fold after T3 treatment in HepG2-TRalpha1 cells. Similar findings were obtained in thyroidectomized rats after T3 application. Cycloheximide treatment did not suppress induction of ARA70 transcription by T3, suggesting that this regulation is direct. A series of deletion mutants of ARA70 promoter fragments in pGL2 plasmid were generated to localize the thyroid hormone response element (TRE). The DNA fragments (-234/-190 or +56/+119) gave 1.55- or 2-fold enhanced promoter activity by T3. Thus, two TRE sites exist in the upstream-regulatory region of ARA70. The TR-TRE interaction was further confirmed with EMSAs. Additionally, ARA70 could interfere with TR/TRE complex formation. Therefore, the data indicated that ARA70 suppresses T3 signaling in a TRE-dependent manner. These experimental results suggest that T3 directly up-regulates ARA70 gene expression. Subsequently, ARA70 negatively regulates T3 signaling.

Thyroid hormone and COUP-TF1 regulate kallikrein-binding protein (KBP) gene expression.

PubMed

Liu, Yan-Yun; Nakatani, Teruyo; Kogai, Takahiko; Mody, Kaizeen; Brent, Gregory A

2011-03-01

Kallikrein-binding protein (KBP) is a component of the kallikrein-kinin system that mediates vasodilation and inhibits tumor growth by antagonizing vascular endothelial growth factor-mediated angiogenesis. We demonstrate that KBP gene expression is repressed by T(3) and modulated by the orphan nuclear receptor, chicken ovalbumin upstream promoter transcription factor 1 (COUP-TF1). In hypothyroid mice, KBP mRNA expression in the testis was increased 2.1-fold compared with euthyroid mice. We have identified two negative thyroid hormone response elements (nTREs) in the mouse KBP gene, nTRE1 located in the 5' flanking region (-53 to -29) and nTRE2, located in the first intron (104-132). We used functional assays, cofactor knockdown, and chromatin immunoprecipitation assays to characterize nTRE1 and nTRE2 in hepatic (HepG2) and testes (GC-1spg) cell lines. Reporter expression directed by both elements was enhanced with addition of thyroid hormone receptor and repressed with the addition of T(3). COUP-TF1 enhanced basal expression of both elements but blunted unliganded thyroid hormone receptor enhancement and T(3) repression of nTRE1 but not nTRE2. Both nTREs bound nuclear corepressor and binding increased in response to T(3). Nuclear corepressor knockdown resulted in loss of T(3) repression of both nTRE1 and nTRE2. COUP-TF1, which usually represses T(3) induction of positive thyroid hormone response elements, reverses T(3) repression mediated by nTRE1 in the mouse KBP gene. Endogenous KBP expression is repressed by T(3) and two functional nTREs, both of which are required, have been characterized in the KBP gene. COUP-TF1 may be an important factor to modulate expression of genes that are repressed by T(3).

Thyroid Hormone and COUP-TF1 Regulate Kallikrein-Binding Protein (KBP) Gene Expression

PubMed Central

Liu, Yan-Yun; Nakatani, Teruyo; Kogai, Takahiko; Mody, Kaizeen

2011-01-01

Kallikrein-binding protein (KBP) is a component of the kallikrein-kinin system that mediates vasodilation and inhibits tumor growth by antagonizing vascular endothelial growth factor-mediated angiogenesis. We demonstrate that KBP gene expression is repressed by T3 and modulated by the orphan nuclear receptor, chicken ovalbumin upstream promoter transcription factor 1 (COUP-TF1). In hypothyroid mice, KBP mRNA expression in the testis was increased 2.1-fold compared with euthyroid mice. We have identified two negative thyroid hormone response elements (nTREs) in the mouse KBP gene, nTRE1 located in the 5′ flanking region (−53 to −29) and nTRE2, located in the first intron (104–132). We used functional assays, cofactor knockdown, and chromatin immunoprecipitation assays to characterize nTRE1 and nTRE2 in hepatic (HepG2) and testes (GC-1spg) cell lines. Reporter expression directed by both elements was enhanced with addition of thyroid hormone receptor and repressed with the addition of T3. COUP-TF1 enhanced basal expression of both elements but blunted unliganded thyroid hormone receptor enhancement and T3 repression of nTRE1 but not nTRE2. Both nTREs bound nuclear corepressor and binding increased in response to T3. Nuclear corepressor knockdown resulted in loss of T3 repression of both nTRE1 and nTRE2. COUP-TF1, which usually represses T3 induction of positive thyroid hormone response elements, reverses T3 repression mediated by nTRE1 in the mouse KBP gene. Endogenous KBP expression is repressed by T3 and two functional nTREs, both of which are required, have been characterized in the KBP gene. COUP-TF1 may be an important factor to modulate expression of genes that are repressed by T3. PMID:21266512

Association between organophosphate pesticides exposure and thyroid hormones in floriculture workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lacasana, Marina, E-mail: marina.lacasana.easp@juntadeandalucia.e; CIBER de Epidemiologia y Salud Publica; Lopez-Flores, Inmaculada

The ability of organophosphate pesticides to disturb thyroid gland function has been demonstrated by experimental studies on animal, but evidence of such effects on human remains scarce. The aim of this study was to assess the association between exposure to organophosphate compounds and serum levels of thyroid hormones in floriculture workers. A longitudinal study was conducted on 136 male subjects from the State of Mexico and Morelos, Mexico, occupationally exposed to organophosphate pesticides, during agricultural periods of high (rainy season) and low (dry season) levels of pesticide application. Using a structured questionnaire, a survey was carried out on sociodemographic characteristics,more » anthropometry, clinical history, alcohol and tobacco consumption, residential chemical exposure, and occupational history. Urine and blood samples were taken the day after pesticide application to determine urine dialkylphosphate (DAP) levels, serum levels of TSH, total T{sub 3}, total T{sub 4}, serum PON1 activity, and serum p,p'-DEE levels. The analysis of the association between DAP levels and thyroid hormonal profile was carried out using multivariate generalized estimating equation (GEE) models. Our results showed an increase in both TSH and T{sub 4} hormones in serum associated with a increase in total dimethylphosphate levels (SIGMADMP) in urine (p-trend < 0.001) and a decrease in total T{sub 3} serum levels with an increase of SIGMADMP levels in the urine (p-trend = 0.053). These results suggest that exposure to organophosphate pesticides may be responsible of increasing TSH and T{sub 4} serum hormone levels and decreasing T{sub 3} serum hormone levels, therefore supporting the hypothesis that organophosphate pesticides act as endocrine disruptors in humans.« less

Assessment of criteria used by veterinary practitioners to diagnose hypothyroidism in sighthounds and investigation of serum thyroid hormone concentrations in healthy Salukis.

PubMed

Shiel, Robert E; Sist, MaryDee; Nachreiner, Raymond F; Ehrlich, Claire P; Mooney, Carmel T

2010-02-01

To assess use of serum thyroid hormone concentrations by veterinarians to diagnose hypothyroidism in sighthounds and to evaluate serum thyroid hormone concentrations in healthy Salukis. Retrospective case series and cross-sectional study. 398 sighthounds of various breeds with a diagnosis of hypothyroidism and 283 healthy Salukis. Pretreatment thyroid hormone assay results from sighthounds subsequently classified as hypothyroid by practitioners were retrieved from a laboratory database. In healthy Salukis, serum concentrations of total thyroxine (T(4)), free T(4), total triiodothyronine (T(3)), free T(3), and thyroid-stimulating hormone (TSH) and antibodies against thyroglobulin and thyroid hormones were assayed. Records indicated hypothyroidism had been diagnosed in 303 (76.1%) sight-hounds on the basis of low serum thyroid hormone concentrations alone and in 30 (7.5%) others despite all thyroid hormone indices being within reference limits. Only 65 (16.3%) dogs had a high TSH concentration or positive thyroglobulin autoantibody result to support the diagnosis. In healthy Salukis, median (reference limits) serum concentrations of total T(4), free T(4), total T(3), free T(3), and TSH were 13.0 nmol/L (2.8 to 40.0 nmol/L), 12.0 pmol/L (2.0 to 30.3 pmol/L), 1.0 nmol/L (0.4 to 2.1 nmol/L), 4.0 pmol/L (1.6 to 7.7 pmol/L), and 0.18 ng/mL (0 to 0.86 ng/mL), respectively. Diagnosis of hypothyroidism by practitioners was most often made without adequate supportive laboratory evidence. Thyroid hormone values in healthy Salukis differed markedly from standard reference limits for some, but not all, thyroid hormone indices. Breed-specific reference limits should be used when interpreting thyroid hormone profiles of sighthounds.

Hormonal changes associated with the transition between nursing and natural fasting in northern elephant seals (Mirounga angustirostris)

NASA Technical Reports Server (NTRS)

Ortiz, Rudy M.; Houser, Dorian S.; Wade, Charles E.; Ortiz, C. Leo

2003-01-01

To better interpret previously described hormonal changes observed during the natural postweaning fast (2-3 months) endured by pups of the northern elephant seal (Mirounga angustirostris), we compared plasma cortisol, thyroid hormones, and leptin in pups (n=5) measured during nursing and fasting periods. Blood samples were taken at four times; early (9 days postpartum) and late (18-22 days postpartum) nursing, and early (second week postweaning) and late (eighth week postweaning) fasting. Plasma cortisol increased 39% between early and late nursing and almost 4-fold by late fasting. After the early nursing period, cortisol and body mass were negatively correlated (y=28.3-0.19 x; R=0.569; p=0.027). Total thyroxine (tT(4)), free T(4) (fT(4)), total triiodothyronine (tT3) and reverse T(3) (rT(3)) were greatest at early nursing and reduced by late nursing and remained so throughout the fast, with the exception of tT(4), which increased between late nursing (17.7+/-2.1 ng mL(-1)) and late fasting (30.1+/-2.8 ng mL(-1)) periods. Leptin remained unaltered among the four sampling periods and was not correlated with body mass. Pups appear to exhibit a shift in the relationship between cortisol and body mass suggesting a potential role for cortisol in the regulation of body fat. The higher concentrations of tT(3) and tT(4) during early nursing may reflect enhanced growth and development during this period, however the increase late in fasting is likely physiologically insignificant and an artifact of reduced metabolic clearance of these hormones. Transition of the pups from nursing to fasting states is characterized by a striking lack of change in cortisol, thyroid hormones, and leptin suggesting that any metabolic alterations associated with this transition may occur independent of these hormones.

Menopausal Symptom Relief and Side Effects Experienced by Women Using Compounded Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 3.

PubMed

Deleruyelle, Laura J

2017-01-01

The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy. A descriptive comparative design was used. Inferential and descriptive statistical procedures including a paired difference t-test, two-sample t-test, and f-tests (percentage, mean, standard deviation, frequency) were run on the Statistical Package for the Social Sciences. The framework used to guide this study was Lenz and Pugh's Theory of Unpleasant Symptoms. Surveys were distributed once to a convenient sample of women aged 35 and older when they dropped off or picked up their prescriptions at a pharmacy. Of the 216 surveys distributed, 70 were returned from those women taking compounded bioidentical hormone replacement therapy and 53 from traditional hormone replacement therapy. The survey contained 15 questions pertaining to age, duration of hormone replacement therapy, type and formulation of hormone replacement therapy, reasons for initiating hormone replacement therapy, symptoms before and one month after hormone replacement therapy, and side effects related to hormone replacement therapy. Included in part 1 of this series of articles was the introduction to the study conducted and the results of the literature review that was conducted for the purpose of examining the current data related to the topic of hormone replacement therapy. Part 2 provided a brief discussion

3,5-Diiodo-L-Thyronine (3,5-T2) Exerts Thyromimetic Effects on Hypothalamus-Pituitary-Thyroid Axis, Body Composition, and Energy Metabolism in Male Diet-Induced Obese Mice

PubMed Central

Lietzow, Julika; Wohlgemuth, Franziska; Hoefig, Carolin S.; Wiedmer, Petra; Schweizer, Ulrich; Köhrle, Josef; Schürmann, Annette

2015-01-01

Effective and safe antiobesity drugs are still needed in face of the obesity pandemic worldwide. Recent interventions in rodents revealed 3,5-diiodo-L-thyronine (3,5-T2) as a metabolically active iodothyronine affecting energy and lipid metabolism without thyromimetic side effects typically associated with T3 administration. Accordingly, 3,5-T2 has been proposed as a potential hypolipidemic agent for treatment of obesity and hepatic steatosis. In contrast to other observations, our experiments revealed dose-dependent thyromimetic effects of 3,5-T2 akin to those of T3 in diet-induced obese male C57BL/6J mice. 3,5-T2 treatment exerted a negative feedback regulation on the hypothalamus-pituitary-thyroid axis, similar to T3. This is demonstrated by decreased expression of genes responsive to thyroid hormones (TH) in pituitary resulting in a suppressed thyroid function with lower T4 and T3 concentrations in serum and liver of 3,5-T2-treated mice. Analyses of hepatic TH target genes involved in lipid metabolism revealed T3-like changes in gene expression and increased type I-deiodinase activity after application of 3,5-T2 (2.5 μg/g body weight). Reduced hepatic triglyceride and serum cholesterol concentrations reflected enhanced lipid metabolism. Desired increased metabolic rate and reduction of different fat depots were, however, compromised by increased food intake preventing significant body weight loss. Moreover, enlarged heart weights indicate potential cardiac side effects of 3,5-T2 beyond hepatic thyromimetic actions. Altogether, the observed thyromimetic effects of 3,5-T2 in several mouse TH target tissues raise concern about indiscriminate administration of 3,5-T2 as powerful natural hormone for the treatment of hyperlipidemia and pandemic obesity. PMID:25322465

3,5-Diiodo-L-thyronine (3,5-t2) exerts thyromimetic effects on hypothalamus-pituitary-thyroid axis, body composition, and energy metabolism in male diet-induced obese mice.

PubMed

Jonas, Wenke; Lietzow, Julika; Wohlgemuth, Franziska; Hoefig, Carolin S; Wiedmer, Petra; Schweizer, Ulrich; Köhrle, Josef; Schürmann, Annette

2015-01-01

Effective and safe antiobesity drugs are still needed in face of the obesity pandemic worldwide. Recent interventions in rodents revealed 3,5-diiodo-L-thyronine (3,5-T2) as a metabolically active iodothyronine affecting energy and lipid metabolism without thyromimetic side effects typically associated with T3 administration. Accordingly, 3,5-T2 has been proposed as a potential hypolipidemic agent for treatment of obesity and hepatic steatosis. In contrast to other observations, our experiments revealed dose-dependent thyromimetic effects of 3,5-T2 akin to those of T3 in diet-induced obese male C57BL/6J mice. 3,5-T2 treatment exerted a negative feedback regulation on the hypothalamus-pituitary-thyroid axis, similar to T3. This is demonstrated by decreased expression of genes responsive to thyroid hormones (TH) in pituitary resulting in a suppressed thyroid function with lower T4 and T3 concentrations in serum and liver of 3,5-T2-treated mice. Analyses of hepatic TH target genes involved in lipid metabolism revealed T3-like changes in gene expression and increased type I-deiodinase activity after application of 3,5-T2 (2.5 μg/g body weight). Reduced hepatic triglyceride and serum cholesterol concentrations reflected enhanced lipid metabolism. Desired increased metabolic rate and reduction of different fat depots were, however, compromised by increased food intake preventing significant body weight loss. Moreover, enlarged heart weights indicate potential cardiac side effects of 3,5-T2 beyond hepatic thyromimetic actions. Altogether, the observed thyromimetic effects of 3,5-T2 in several mouse TH target tissues raise concern about indiscriminate administration of 3,5-T2 as powerful natural hormone for the treatment of hyperlipidemia and pandemic obesity.

Thyroid hormone and obesity.

PubMed

Pearce, Elizabeth N

2012-10-01

To review several of the most recent and most important clinical studies regarding the effects of thyroid treatments on weight change, associations between thyroid status and weight, and the effects of obesity and weight change on thyroid function. Weight decreases following treatment for hypothyroidism. However, following levothyroxine treatment for overt hypothyroidism, weight loss appears to be modest and mediated primarily by loss of water weight rather than fat. There is conflicting evidence about the effects of thyroidectomy on weight. In large population studies, even among euthyroid individuals, serum thyroid-stimulating hormone is typically positively associated with body weight and BMI. Both serum thyroid-stimulating hormone and T3 are typically increased in obese compared with lean individuals, an effect likely mediated, at least in part, by leptin. Finally, there is no consistent evidence that thyroid hormone treatment induces weight loss in obese euthyroid individuals, but thyroid hormone analogues may eventually be useful for weight loss. The interrelationships between body weight and thyroid status are complex.

Molecular characterization of thyroid hormone-inhibited atrial L-type calcium channel expression: implication for atrial fibrillation in hyperthyroidism.

PubMed

Chen, Wei-Jan; Yeh, Yung-Hsin; Lin, Kwang-Huei; Chang, Gwo-Jyh; Kuo, Chi-Tai

2011-03-01

Atrial fibrillation (AF) is a common complication in hyperthyroidism. Earlier studies demonstrate that thyroid hormone decreases L-type calcium channel (LCC) current expression with resultant shortening of action potential duration (APD), providing a substrate for AF. The aim of this study was to investigate the potential mechanism underlying the regulatory effect of thyroid hormone on LCC. In a hyperthyroid rat model, thyroid hormone (triiodothyronine [T3]) administration down-regulated atrial LCC expression. In vitro, treatment of murine atrial myocytes (HL-1) with T3 decreased the expression of LCC and its current, resulting in abbreviation of APD. Furthermore, T3 inhibited the activation of cyclic AMP response element (CRE)-binding protein (CREB), including phosphorylation at Ser133 and its nuclear translocation. Transient transfection studies in HL-1 cells indicated that T3 reduced LCC promoter activity. Deletion and mutation analysis of the LCC promoter region along with chromatin immunoprecipitation using anti-CREB antibody showed that CRE was essential for T3-mediated LCC gene expression. Transfection of dominant-negative CREB (mutated Ser133) and mutant thyroid hormone receptor (TR, mutated Cys51) abolished the T3-dependent effects, suggesting an association between both transcriptional factors. Co-immunoprecipitation documented an increased binding of TR with CREB after T3 treatment. The transcriptional cross-talk 3 between TR and CREB bound to CRE mediates T3-inhibited CREB activity and LCC expression. Thyroid hormone-induced TR binding of CREB inhibits CREB activity and LCC current expression, which may contribute to AF. These findings provide an important mechanistic insight into hyperthyroidism-induced AF.

Maternal thyroid hormone trajectories during pregnancy and child behavioral problems.

PubMed

Endendijk, Joyce J; Wijnen, Hennie A A; Pop, Victor J M; van Baar, Anneloes L

2017-08-01

There is ample evidence demonstrating the importance of maternal thyroid hormones, assessed at single trimesters in pregnancy, for child cognition. Less is known, however, about the course of maternal thyroid hormone concentrations during pregnancy in relation to child behavioral development. Child sex might be an important moderator, because there are sex differences in externalizing and internalizing behavioral problems. The current study examined the associations between maternal thyroid hormone trajectories versus thyroid assessments at separate trimesters of pregnancy and child behavioral problems, as well as sex differences in these associations. In 442 pregnant mothers, serum levels of TSH and free T4 (fT4) were measured at 12, 24, and 36weeks gestation. Both mothers and fathers reported on their children's behavioral problems, between 23 and 60months of age. Latent growth mixture modeling was used to determine the number of different thyroid hormone trajectories. Three trajectory groups were discerned: 1) highest and non-increasing TSH with lowest fT4 that decreased least of the three trajectories; 2) increasing TSH and decreasing fT4 at intermediate levels; 3) lowest and increasing TSH with highest and decreasing fT4. Children of mothers with the most flattened thyroid hormone trajectories (trajectory 1) showed the most anxiety/depression symptoms. The following trimester-specific associations were found: 1) lower first-trimester fT4 was associated with more child anxiety/depression, 2) higher first-trimester TSH levels were related to more attention problems in boys only. A flattened course of maternal thyroid hormone concentrations during pregnancy was a better predictor of child anxiety/depression than first-trimester fT4 levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Thyroid hormone modulates food intake and glycemia via ghrelin secretion in Zucker fatty rats.

PubMed

Patel, K; Joharapurkar, A; Dhanesha, N; Patel, V; Kshirsagar, S; Raval, P; Raval, S; Jain, M R

2014-10-01

Hyperthyroidism is known to increase food intake and central administration of thyroid hormone shows acute orexigenic effects in rodents. We investigated whether T3 influences appetite and glucose homeostasis by modulating circulating ghrelin, an important orexigenic hormone, in Zucker fatty rats. The acute anorectic effects of T3 and ghrelin mimetic MK-0677 were studied in rats trained for fasting induced food intake. The serum concentration of T3, ghrelin, glucose, triglycerides, and liver glycogen were estimated. The involvement of sympathetic nervous system was evaluated by conducting similar experiments in vagotomized rats. T3 increased food intake and glucose in rats over 4 h, with increase in serum T3 and decrease in liver glycogen. T3 treatment was associated with increase in serum ghrelin. An additive effect on appetite and glucose was observed when T3 (oral) was administered with central (intracerebroventricular) administration of a ghrelin mimetic, MK-0677. Ghrelin antagonist, compound 8a, antagonized the hyperglycemic and hyperphagic effects of T3. In vagotomized rats, T3 did not show increase in appetite as well as glucose. Serum ghrelin levels were unchanged in these animals after T3 treatment. However, T3 showed increase in serum triglyceride levels indicating its peripheral lipolytic effect, in vagotomized as well as sham treated animals. To conclude, acute orexigenic and hyperglycemic effects of T3 are associated with ghrelin secretion and activity. This effect seems to be mediated via vagus nerves, and is independent of glucoregulatory hormones. © Georg Thieme Verlag KG Stuttgart · New York.

Molecular mechanisms of corticosteroid synergy with thyroid hormone during tadpole metamorphosis

PubMed Central

Bonett, Ronald M.; Hoopfer, Eric D.; Denver, Robert J.

2010-01-01

Corticosteroids (CS) act synergistically with thyroid hormone (TH) to accelerate amphibian metamorphosis. Earlier studies showed that CS increase nuclear 3,5,3′-triiodothyronine (T3) binding capacity in tadpole tail, and 5′ deiodinase activity in tadpole tissues, increasing the generation of T3 from thyroxine (T4). In the present study we investigated CS synergy with TH by analyzing expression of key genes involved in TH and CS signaling using tadpole tail explant cultures, prometamorphic tadpoles, and frog tissue culture cells (XTC-2 and XLT-15). Treatment of tail explants with T3 at 100 nM, but not at 10 nM caused tail regression. Corticosterone (CORT) at three doses (100, 500, 3400 nM) had no effect or increased tail size. T3 at 10 nM plus CORT caused tails to regress similar to 100 nM T3. Thyroid hormone receptor beta (TRβ) mRNA was synergistically upregulated by T3 plus CORT in tail explants, tail and brain in vivo, and tissue culture cells. The activating 5′ deiodinase type 2 (D2) mRNA was induced by T3 and CORT in tail explants and tail in vivo. Thyroid hormone increased expression of glucocorticoid (GR) and mineralocorticoid receptor (MR) mRNAs. Our findings support that the synergistic actions of TH and CS in metamorphosis occur at the level of expression of genes for TRβ and D2, enhancing tissue sensitivity to TH. Concurrently, TH enhances tissue sensitivity to CS by upregulating GR and MR. Environmental stressors can modulate the timing of tadpole metamorphosis in part by CS enhancing the response of tadpole tissues to the actions of TH. PMID:20338173

Gamete ripening and hormonal correlates in three strains of lake trout

USGS Publications Warehouse

Foster, N.R.; O'Connor, D.V.; Schreck, C.B.

1993-01-01

In our 2-year laboratory study of hatchery-reared adult lake trout Salvelinus namaycush of the Seneca Lake, Marquette (Lake Superior Lean), and Jenny Lake strains, we compared gamete ripening times and changes in plasma concentrations of seven hormones. If interstrain differences in these traits were found, such differences might help explain the apparent failure of stocked fish of these strains to develop large, naturally reproducing populations in the Great Lakes. The complex temporal changes in plasma hormone levels that occur during sexual maturation in lake trout have not been previously described. We detected little evidence of temporal isolation that would prevent interbreeding among the three strains. Strain had no effect on ovulation date (OD) in either year. Strain did not affect spermiation onset date (SOD) in year 1 but did in year 2, when the mean SOD of Jenny Lake males was earlier than that of Seneca Lake males but not different from that of Marquette males. Hormonal data were normalized around ODs for individual females and SODs for individual males. In females, estradiol-17β (E2) was highest 8 weeks before the OD; the highest testosterone (T) level occurred 6 weeks before the OD, and the next highest level occurred simultaneously with the highest level of 11-ketotestosterone (11-KT) 2 weeks before the OD. Plasma levels of 17∝-hydroxy-20β-dihydroprogesterone (DHP) peaked 1 week before the OD, then abruptly declined immediately after. Cortisol (F), triiodothyronine (T3), and thyroxine (T4) were highly variable, but F was the only hormone that showed no trend with week in either year. In males, plasma E2 levels were highest 3 weeks before the SOD, highest levels of T and of 11-KT occurred simultaneously 2 weeks after the SOD, and DHP peaked 5 weeks after the SOD and 3 weeks after the highest levels of T and 11-KT. As in females, plasma levels of F, T3, and T4 were highly variable, and F was the only hormone that showed no trend with week in

Two novel LHX3 mutations in patients with combined pituitary hormone deficiency including cervical rigidity and sensorineural hearing loss.

PubMed

Ramzan, Khushnooda; Bin-Abbas, Bassam; Al-Jomaa, Lolwa; Allam, Rabab; Al-Owain, Mohammed; Imtiaz, Faiqa

2017-03-16

Congenital combined pituitary hormone deficiency (CPHD) is a rare heterogeneous group of conditions. CPHD-type 3 (CPHD3; MIM# 221750) is caused by recessive mutations in LHX3, a LIM-homeodomain transcription factor gene. The isoforms of LHX3 are critical for pituitary gland formation and specification of the anterior pituitary hormone-secreting cell types. They also play distinct roles in the development of neuroendocrine and auditory systems. Here, we summarize the clinical, endocrinological, radiological and molecular features of three patients from two unrelated families. Clinical evaluation revealed severe CPHD coupled with cervical vertebral malformations (rigid neck, scoliosis), mild developmental delay and moderate sensorineural hearing loss (SNHL). The patients were diagnosed with CPHD3 based on the array of hormone deficiencies and other associated syndromic symptoms, suggestive of targeted LHX3 gene sequencing. A novel missense mutation c.437G > T (p. Cys146Phe) and a novel nonsense mutation c.466C > T (p. Arg156Ter), both in homozygous forms, were found. The altered Cys146 resides in the LIM2 domain of the encoded protein and is a phylogenetically conserved residue, which mediates LHX3 transcription factor binding with a zinc cation. The p. Arg156Ter is predicted to result in a severely truncated protein, lacking the DNA binding homeodomain. Considering genotype/phenotype correlation, we suggest that the presence of SNHL and limited neck rotation should be considered in the differential diagnosis of CPHD3 to facilitate molecular diagnosis. This report describes the first LHX3 mutations from Saudi patients and highlights the importance of combining molecular diagnosis with the clinical findings. In addition, it also expands the knowledge of LHX3-related CPHD3 phenotype and the allelic spectrum for this gene.

Activation of Sox3 Gene by Thyroid Hormone in the Developing Adult Intestinal Stem Cell During Xenopus Metamorphosis

PubMed Central

Sun, Guihong; Fu, Liezhen; Wen, Luan

2014-01-01

The maturation of the intestine into the adult form involves the formation of adult stem cells in a thyroid hormone (T3)-dependent process in vertebrates. In mammals, this takes place during postembryonic development, a period around birth when the T3 level peaks. Due to the difficulty of manipulating late-stage, uterus-enclosed embryos, very little is known about the development of the adult intestinal stem cells. Interestingly, the remodeling of the intestine during the T3-dependent amphibian metamorphosis mimics the maturation of mammalian intestine. Our earlier microarray studies in Xenopus laevis revealed that the transcription factor SRY (sex-determining region Y)-box 3 (Sox3), well known for its involvement in neural development, was upregulated in the intestinal epithelium during metamorphosis. Here, we show that Sox3 is highly and specifically expressed in the developing adult intestinal progenitor/stem cells. We further show that its induction by T3 is independent of new protein synthesis, suggesting that Sox3 is directly activated by liganded T3 receptor. Thus, T3 activates Sox3 as one of the earliest changes in the epithelium, and Sox3 in turn may facilitate the dedifferentiation of the larval epithelial cells into adult stem cells. PMID:25211587

New Insights into Thyroid Hormone Action

PubMed Central

Mendoza, Arturo; Hollenberg, Anthony N.

2017-01-01

Thyroid hormones (TH) are endocrine messengers essential for normal development and function of virtually every vertebrate. The hypothalamic-pituitary-thyroid axis is exquisitely modulated to maintain nearly constant TH (T4 and T3) concentrations in circulation. However peripheral tissues and the CNS control the intracellular availability of TH, suggesting that circulating concentrations of TH are not fully representative of what each cell type sees. Indeed, recent work in the field has identified that TH transporters, deiodinases and thyroid hormone receptor coregulators can strongly control tissue-specific sensitivity to a set amount of TH. Furthermore, the mechanism by which the thyroid hormone receptors regulate target gene expression can vary by gene, tissue and cellular context. This review will highlight novel insights into the machinery that controls the cellular response to TH, which include unique signaling cascades. These findings shed new light into the pathophysiology of human diseases caused by abnormal TH signaling. PMID:28174093

Thyrotropin-induced hyperthyroidism caused by selective pituitary resistance to thyroid hormone. A new syndrome of "inappropriate secretion of TSH".

PubMed Central

Gershengorn, M C; Weintraub, B D

1975-01-01

An 18-yr-old woman with clinical and laboratory features of hyperthyroidism had persistently elevated serum levels of immunoreative thyrotropin (TSH). During 11 yr of follow-up there had been no evidence of a pituitary tumor. After thyrotropin-releasing hormone (TRH), there was a marked increase in TSH and secondarily in triiodothyronine (T3), the latter observation confirming the biologic activity of the TSH. Exogenous T3 raised serum T3 and several measurements of peripheral thyroid hormone effect, while decreasing serum TSH, thyroxine (T4), and thyroidal radioiodine uptake. After T3, the TRH-stimulated TSH response was decreased but was still inappropriate for the elevated serum T3 levels. Dexamethasone reduced serum TSH but did not inhibit TRH stimulation of TSH. Propylthiouracil reduced serum T4 and T3 and raised TSH. This patient represents a new syndrome of TSH-induced hyperthyroidism, differing from previous reports in the absence of an obvious pituitary tumor and in the responsiveness of the TSH to TRH stimulation and thyroid hormone suppression. This syndrome appears to be caused by a selective, partial resistance of the pituitary to the action of thyroid hormone. This case is also compared with previous reports in the literature of patients with elevated serum levels of immunoreactive TSH in the presence of elevated total and free thyroid hormones. A classification of these cases, termed "inappropriate secretion of TSH," is proposed. PMID:1159077

Thyroid hormone concentrations differ between donkeys and horses.

PubMed

Mendoza, F J; Perez-Ecija, R A; Toribio, R E; Estepa, J C

2013-03-01

Reference intervals for thyroid hormones (TH) concentrations have not been previously established for donkeys, leading to potential misdiagnosis of thyroid disease. To determine the normal values of TH in healthy adult donkeys and compare them to TH values from healthy adult horses. Thirty-eight healthy Andalusian donkeys and 19 healthy Andalusian horses from 2 different farms were used. Donkeys were divided into 3 age groups: <5, 5-10 and >11 years and into 2 gender groups. Serum concentrations of fT3, tT3, rT3, fT4 and tT4 were quantified by radioimmunoassay. All blood samples were collected the same day in the morning. None of the animals had received any treatment for 30 days prior to sampling or had any history of disease. Both farms were in close proximity and under similar management. Differences between groups were determined using a one-way ANOVA analysis followed by Fisher's LSD test. P<0.05 was considered significant. Serum TH concentrations were higher in donkeys than in horses (P<0.01). Donkeys <5 years had higher serum rT3, fT4 and tT4 concentrations than donkeys >5 years (P<0.05). Furthermore, older donkeys (>11 years) had lower serum fT3 and tT3 concentrations than younger donkeys' groups (<5 and 5-10 years, P<0.05). TH concentrations were not different between genders (fT3: P = 0.06; tT3: P = 0.08; rT3: P = 0.15; fT4: P = 0.89; and tT4: P = 0.19). Thyroid hormone concentrations are different between healthy adult donkeys and horses. Establishing species-specific TH reference ranges is important when evaluating clinicopathologic data in equids in order to avoid the misdiagnosis of thyroid gland dysfunction. Further studies to elucidate the physiological mechanisms leading to these differences are warranted. © 2012 EVJ Ltd.

Thyroid hormone elevations during acute psychiatric illness: relationship to severity and distinction from hyperthyroidism.

PubMed

Roca, R P; Blackman, M R; Ackerley, M B; Harman, S M; Gregerman, R I

1990-01-01

Acute psychiatric illness may be accompanied by transient hyperthyroxinemia. The mechanism of this phenomenon was examined by determining the role of thyrotropin (TSH) in the genesis of this state. Serial measurements of TSH, thyroxine (T4), free T4 index (FT4I), triiodothyronine (T3), and free T3 index (FT3I) were performed in 45 acutely hospitalized patients with major psychiatric disorders. Twenty-two (49%) patients exhibited significant elevations (greater than or equal to 2 SD above mean value of controls) of one or more thyroid hormone (or index) levels. Among depressed patients with elevated FT4I, TSH was higher (p less than .05) on the day of the peak FT4I than on the day of the FT4I nadir. There were significant positive correlations between psychiatric symptom severity and levels of FT4I among both depressed (p less than .01) and schizophrenic (p less than .025) patients. These data show that elevations of T4, FT4I, T3, and FT3I are common among psychiatric inpatients, especially early in their hospitalization, and that levels of thyroid hormones are correlated with severity of psychiatric symptomatology. TSH is higher early in the acute phase of illness and is not suppressed in the face of elevated thyroid hormone levels, a finding that distinguishes this phenomenon from ordinary hyperthyroidism. Elevations of peripheral thyroid hormone levels, particularly among depressed patients, may result from a centrally-mediated hypersecretion of TSH.

Dronerarone acts as a selective inhibitor of 3,5,3'-triiodothyronine binding to thyroid hormone receptor-alpha1: in vitro and in vivo evidence.

PubMed

Van Beeren, H C; Jong, W M C; Kaptein, E; Visser, T J; Bakker, O; Wiersinga, W M

2003-02-01

Dronedarone (Dron), without iodine, was developed as an alternative to the iodine-containing antiarrhythmic drug amiodarone (AM). AM acts, via its major metabolite desethylamiodarone, in vitro and in vivo as a thyroid hormone receptor alpha(1) (TRalpha(1)) and TRbeta(1) antagonist. Here we investigate whether Dron and/or its metabolite debutyldronedarone inhibit T(3) binding to TRalpha(1) and TRbeta(1) in vitro and whether dronedarone behaves similarly to amiodarone in vivo. In vitro, Dron had a inhibitory effect of 14% on the binding of T(3) to TRalpha(1), but not on TRbeta(1). Desethylamiodarone inhibited T(3) binding to TRalpha(1) and TRbeta(1) equally. Debutyldronedarone inhibited T(3) binding to TRalpha(1) by 77%, but to TRbeta(1) by only 25%. In vivo, AM increased plasma TSH and rT(3), and decreased T(3). Dron decreased T(4) and T(3), rT(3) did not change, and TSH fell slightly. Plasma total cholesterol was increased by AM, but remained unchanged in Dron-treated animals. TRbeta(1)-dependent liver low density lipoprotein receptor protein and type 1 deiodinase activities decreased in AM-treated, but not in Dron-treated, animals. TRalpha(1)-mediated lengthening of the QTc interval was present in both AM- and Dron-treated animals. The in vitro and in vivo findings suggest that dronedarone via its metabolite debutyldronedarone acts as a TRalpha(1)-selective inhibitor.

Covalent modification of proteins by ligands of steroid hormone receptors.

PubMed Central

Takahashi, N; Breitman, T R

1992-01-01

Retinoylation, acylation with retinoic acid (RA), is a covalent modification of proteins occurring in a variety of eukaryotic cell lines. In this study, we found that proteins in HL-60 cells were labeled by 17 beta-[3H]estradiol (E2), [3H]progesterone (Pg), 1 alpha,25-dihydroxy[3H]vitamin D3 [1,25(OH)2D3], [125I]triiodothyronine (T3), [125I]thyroxine (T4), and [3H]prostaglandin E2 (PGE2). All of these hormones, except PGE2, are ligands of the steroid hormone receptor family. Addition to the growth medium of 5 microM ketoconazole, an inhibitor of cytochrome P450-dependent enzymes, increased about 2-fold the labeling of proteins by T3, T4, 1,25(OH)2D3, and PGE2. In contrast, ketoconazole did not change markedly the extent of labeling by RA, E2, or Pg. Alkaline methanolysis, which cleaves ester bonds, released variable percentages of the radioactive ligands bound to protein. These values were about 80% for RA and PGE2; 50% for T3, T4, and Pg; and 20% for E2 and 1,25(OH)2D3. Treatment with thioether-cleavage reagents, iodomethane or Raney nickel catalyst, released < 2% of the covalently bound ligands. Two-dimensional polyacrylamide gel electrophoresis patterns of labeled proteins were unique for each ligand. Proteins of M(r) 47,000 and 51,000 were labeled by RA, E2, T3, and T4. These proteins had the same mobilities as RI and RII, the cAMP-binding regulatory subunits of type I and type II cAMP-dependent protein kinases. 1,25(OH)2D3 also bound to proteins of M(r) 47,000 and 51,000. However, these proteins had pI values different from those of RI or RII. These results suggest that some activities of ligands of the steroid hormone receptor family and of PGE2 may be mediated by their covalent modification of proteins. Images PMID:1438281

Covalent modification of proteins by ligands of steroid hormone receptors.

PubMed

Takahashi, N; Breitman, T R

1992-11-15

Retinoylation, acylation with retinoic acid (RA), is a covalent modification of proteins occurring in a variety of eukaryotic cell lines. In this study, we found that proteins in HL-60 cells were labeled by 17 beta-[3H]estradiol (E2), [3H]progesterone (Pg), 1 alpha,25-dihydroxy[3H]vitamin D3 [1,25(OH)2D3], [125I]triiodothyronine (T3), [125I]thyroxine (T4), and [3H]prostaglandin E2 (PGE2). All of these hormones, except PGE2, are ligands of the steroid hormone receptor family. Addition to the growth medium of 5 microM ketoconazole, an inhibitor of cytochrome P450-dependent enzymes, increased about 2-fold the labeling of proteins by T3, T4, 1,25(OH)2D3, and PGE2. In contrast, ketoconazole did not change markedly the extent of labeling by RA, E2, or Pg. Alkaline methanolysis, which cleaves ester bonds, released variable percentages of the radioactive ligands bound to protein. These values were about 80% for RA and PGE2; 50% for T3, T4, and Pg; and 20% for E2 and 1,25(OH)2D3. Treatment with thioether-cleavage reagents, iodomethane or Raney nickel catalyst, released < 2% of the covalently bound ligands. Two-dimensional polyacrylamide gel electrophoresis patterns of labeled proteins were unique for each ligand. Proteins of M(r) 47,000 and 51,000 were labeled by RA, E2, T3, and T4. These proteins had the same mobilities as RI and RII, the cAMP-binding regulatory subunits of type I and type II cAMP-dependent protein kinases. 1,25(OH)2D3 also bound to proteins of M(r) 47,000 and 51,000. However, these proteins had pI values different from those of RI or RII. These results suggest that some activities of ligands of the steroid hormone receptor family and of PGE2 may be mediated by their covalent modification of proteins.

Effects of two estroprogestins containing ethynilestradiol 30 microg and drospirenone 3 mg and ethynilestradiol 30 microg and chlormadinone 2 mg on skin and hormonal hyperandrogenic manifestations.

PubMed

Lello, Stefano; Primavera, Grazia; Colonna, Laura; Vittori, Giorgio; Guardianelli, Francesca; Sorge, Roberto; Raskovic, Desanka

2008-12-01

Hyperandrogenic manifestation in women, such as seborrhea, acne and increased hair growth are common reasons of psychological distress. Skin appearance is very important for young women. This study evaluated the hormonal and skin effects of two estroprogestins (EPs) containing ethinyl-estradiol (EE) 30 microg associated with drospirenone (DRSP) 3 mg or chlormadinone acetate (CMA) 2 mg, respectively. Fifty-five women with signs and symptoms of hyperandrogenism (seborrhea, acne and increased hair growth) were enrolled in the study; randomly, 30 women were treated with EE 30 microg + DRSP 3 mg and 25 with EE 30 microg + CMA 2 mg. Follicle-stimulating hormone (FSH), luteinising hormone (LH), 17-hydroxyprogesterone (17OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG) and free androgen index (T x 100/SHBG, FAI) were assessed at baseline, and after 3 and 6 months of treatment with EPs. Effects on seborrhea, acne and increased hair growth (as Ferriman-Gallwey score) were also evaluated at the same time points. Finally, skin hydration, transepidermal water loss (TEWL) and skin homogeneity were studied with non-invasive technique during the study. Treatment for 6 months with both EPs decreased significantly the circulating androgen levels (A, T, DHEAS) and FAI, and increased SHBG levels; also skin pattern was improved. EP containing EE and DRSP was better than EP containing EE and CMA as for skin changes, as seborrhea, acne, increased hair, hydration, homogeneity and overall quality of the skin; moreover, hormonal changes (as FAI) under therapy were more pronounced with EE/DRSP than EE/CMA. These effects may be considered in EP choice and could be important in improving patient's compliance and quality of life in hyperandrogenic women.

Variation with semilunar periodicity of plasma steroid hormone production in the mudskipper Boleophthalmus pectinirostris.

PubMed

Wang, Qiong; Hong, Wanshu; Chen, Shixi; Zhang, Qiyong

2008-02-01

Variation in the production of the plasma steroid hormones E(2), 17alpha-OHP and T in females and T and 11-KT in males, was investigated in the mudskipper Boleophthalmus pectinirostris during the spawning season. Females with oocytes at the vitellogenic stage (GSI 5.97-6.86%) and mature males with GSI of 0.255-0.288% were collected at intervals of 3-4 days within the two complete semilunar cycles from May 31 to June 30, 2006. The results showed that variations in the levels of plasma steroid hormones were synchronized obviously with semilunar periodicity in both females and males. Each steroid hormone level exhibited two cycles, each cycle with a peak. In females, the first peaks in plasma E(2), 17alpha-OHP and T levels were observed 3 days after the first lunar quarter, and the second ones, 4 days after the last lunar quarter. In males, the first peaks of plasma T and 11-KT levels occurred 3 days after the first lunar quarter, and the second ones, at the last lunar quarter. The fact that, in the present study, changes in the levels of plasma steroid hormones were synchronized with semilunar periodicity, although the fish were at the same stages of gonadal development, suggests that variation of plasma steroid hormones is basically regulated by biological rhythms (Zeitgebers), and that tidal movement (with its semilunar periodicity) is the major environmental factor stimulating steroid hormone production in B. pectinirostris.

Pseudohypoparathyroidism: defective excretion of 3′,5′-AMP in response to parathyroid hormone

PubMed Central

Chase, Lewis R.; Melson, G. Leland; Aurbach, G. D.

1969-01-01

Urinary excretion of cyclic adenosine 3′,5′-monophosphate (3′,5′-AMP) was tested in normal subjects and patients with pseudohypoparathyroidism, idiopathic hypoparathyroidism, surgical hypoparathyroidism, and pseudopseudohypoparathyroidism under basal conditions and after a 15 min infusion of purified parathyroid hormone. Basal excretion of the nucleotide was less than normal in the patients with hypocalcemic disorders and greater than normal in pseudopseudohypoparathyroidism. Parathyroid hormone caused a marked increase in excretion of 3′,5′-AMP in all subjects except those with pseudohypoparathyroidism; nine patients with this disorder did not respond to the hormone and four showed a markedly deficient response. Radioimmunoassay showed that parathyroid hormone circulated in increased amounts in plasma from patients with pseudohypoparathyroidism and became undetectable when serum calcium was increased above 12 mg/100 ml. Suppression of parathyroid hormone secretion by induction of hypercalcemia did not alter the deficient response to exogenous hormone. The results indicate that: (a) parathyroid hormone circulates in abnormally high concentrations in pseudohypoparathyroidism and secretion of the hormone responds normally to physiological control by calcium; (b) testing urinary excretion of 3′,5′-AMP in response to infusion of purified parathyroid hormone appears to be an accurate and sensitive index for establishing the diagnosis of pseudohypoparathyroidism; and (c) the metabolic defect of the disorder can be accounted for by a lack of or defective form of parathyroid hormone-sensitive adenyl cyclase in bone and kidney. PMID:4309802

THE RELATIONSHIP BETWEEN SEX HORMONES, SEX HORMONE BINDING GLOBULIN AND PERIPHERAL ARTERY DISEASE IN OLDER PERSONS

PubMed Central

Maggio, M; Cattabiani, C; Lauretani, F; Artoni, A; Bandinelli, S; Schiavi, G; Vignali, A; Volpi, R; Ceresini, G; Lippi, G; Aloe, R; De Vita, F; Giallauria, F; McDermott, MM; Ferrucci, L; Ceda, GP

2014-01-01

Objective The prevalence of peripheral artery disease (PAD) increases with aging and is higher in persons with metabolic syndrome and diabetes. PAD is associated with adverse outcomes, including frailty and disability. The protective effect of testosterone and sex hormone binding globulin (SHBG) for diabetes in men suggests that the biological activity of sex hormones may affect PAD, especially in older populations. Methods Nine hundred and twenty-one elderly subjects with data on SHBG, testosterone (T), estradiol (E2) were selected from InCHIANTI study. PAD was defined as an Ankle-Brachial Index (ABI) <0.90. Logistic regression models adjusted for age (Model 1), age, BMI, insulin, interleukin-6, physical activity, smoking, chronic diseases including metabolic syndrome (Model 2), and a final model including also sex hormones (Model 3) were performed to test the relationship between SHBG, sex hormones and PAD. Results The mean age (± SD) of the 419 men and 502 women was 75.0 ± 6.8 years (Sixty two participants (41 men, 21 women) had ABI<0.90. Men with PAD had SHBG levels lower than men without PAD (p=0.03). SHBG was negatively and independently associated with PAD in men (p=0.028). but not in women. The relationship was however attenuated after adjusting for sex hormones (p=0.07). The E2 was not significantly associated with PAD in both men and women. In women, but not in men, T was positively associated with PAD, even after adjusting for multiple confounders, including E2 (p=0.01). Conclusions Low SHBG and high T levels are significantly and independently associated with the presence of PAD in older men and women, respectively. PMID:23102785

T cell lymphoblastic lymphoma/leukemia within an adrenocorticotropic hormone and thyroid stimulating hormone positive pituitary adenoma: A cytohistological correlation emphasizing importance of intra-operative squash smear.

PubMed

Gupta, Rakesh K; Saran, Ravindra K; Srivastava, Arvind K; Jagetia, Anita; Garg, Lalit; Sharma, Mehar C

2017-08-01

We present a rare case of primary pituitary T cell lymphoma/leukemia (T-LBL) in association with adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH) expressing pituitary adenoma in a 55-year-old woman highlighting the importance of intra-operative squash smears examination. The patient presented with complaints of headache, diminution of vision and recent onset altered sensorium. MRI revealed a mass lesion in the sellar-suprasellar region with non-visualization of pituitary gland separately, extending to involve adjacent structures diagnosed as invasive pituitary macroadenoma. Intra-operative tissue was sent for squash smear examination. The cytology showed a tumor comprising of sheets of immature lymphoid cells intermixed with clusters of pituitary acinar cells with many mitoses and tingible body macrophages. A diagnosis of presence of immature lymphoid cells within the pituitary was offered and differentials of infiltration by lymphoma cells from systemic disease versus primary central nervous lymphoma-like lymphoma arising in the pituitary adenoma were considered. Later paraffin section examination and immunohistochemistry corroborated with the squash findings and a final diagnosis of primary pituitary T cell lymphoma/leukemia in association with ACTH and TSH expressing pituitary adenoma was made. To date, only six cases of primary pituitary T cell lymphomas, including three T-LBL cases, have been reported. This is the seventh case and first one additionally describing cytohistological correlation and importance of intra-operative cytology. © 2017 Japanese Society of Neuropathology.

Thyroid and Cortisol hormones in Attention Deficit Hyperactivity Disorder: A case-control study.

PubMed

Kuppili, Pooja Patnaik; Pattanayak, Raman Deep; Sagar, Rajesh; Mehta, Manju; Vivekanandhan, S

2017-08-01

There is paucity of research in the putative role of hormonal biomarkers in Attention Deficit Hyperactivity Disorder (ADHD). The current study aimed to analyze the clinical profile, socio-demographic status, co-morbidity, hormonal biomarkers namely Thyroid hormones and Cortisol in children with ADHD and compare them with healthy controls and to explore the association of the hormonal biomarkers with severity of ADHD. Thirty children with DSM-IV TR diagnosis of ADHD were assessed using semi structured proforma, Conners' Parent Rating Scale revised short (CPRS - R: S) , Mini international neuropsychiatric interview for children and adolescents and Childrens' Global Assessment Scale as well as serum levels of total Triiodothyronine (T3) ,total Thyroxine (T4) , Thyroid Stimulating Hormone (TSH) and Cortisol using chemiluminescent immunometric assay and compared with 30 age- and gender -matched controls. The typical profile of cases of ADHD was of a male with mean age of 9.47 years (S.D=2.43) belonging to Hyperactive subtype of ADHD. Serum T4 was significantly lower in cases compared to controls. No significant difference was found in serum T3, TSH and Cortisol levels. No significant correlation between the CPRS : R-S scores and the hormonal biomarkers. There is need for exploration of Serum T4 as putative biomarker for ADHD with replication in future studies. It may also be important to report the negative finding of Cortisol as a biomarker of ADHD in the context of effective utilization of resources for research with special relevance to resource deficit developing countries. Copyright © 2017 Elsevier B.V. All rights reserved.

Ghrelin inhibits proliferation and increases T-type Ca{sup 2+} channel expression in PC-3 human prostate carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diaz-Lezama, Nundehui; Hernandez-Elvira, Mariana; Sandoval, Alejandro

Research highlights: {yields} Ghrelin decreases prostate carcinoma PC-3 cells proliferation. {yields} Ghrelin favors apoptosis in PC-3 cells. {yields} Ghrelin increase in intracellular free Ca{sup 2+} levels in PC-3 cells. {yields} Grelin up-regulates expression of T-type Ca{sup 2+} channels in PC-3 cells. {yields} PC-3 cells express T-channels of the Ca{sub V}3.1 and Ca{sub V}3.2 subtype. -- Abstract: Ghrelin is a multifunctional peptide hormone with roles in growth hormone release, food intake and cell proliferation. With ghrelin now recognized as important in neoplastic processes, the aim of this report is to present findings from a series of in vitro studies evaluating themore » cellular mechanisms involved in ghrelin regulation of proliferation in the PC-3 human prostate carcinoma cells. The results showed that ghrelin significantly decreased proliferation and induced apoptosis. Consistent with a role in apoptosis, an increase in intracellular free Ca{sup 2+} levels was observed in the ghrelin-treated cells, which was accompanied by up-regulated expression of T-type voltage-gated Ca{sup 2+} channels. Interestingly, T-channel antagonists were able to prevent the effects of ghrelin on cell proliferation. These results suggest that ghrelin inhibits proliferation and may promote apoptosis by regulating T-type Ca{sup 2+} channel expression.« less

Excess thyroid hormone inhibits embryonic neural stem/progenitor cells proliferation and maintenance through STAT3 signalling pathway.

PubMed

Chen, Chunhai; Zhou, Zhou; Zhong, Min; Li, Maoquan; Yang, Xuesen; Zhang, Yanwen; Wang, Yuan; Wei, Aimin; Qu, Mingyue; Zhang, Lei; Xu, Shangcheng; Chen, Shude; Yu, Zhengping

2011-07-01

Hyperthyroidism is prevalent during pregnancy, but little is known about the effects of excess thyroid hormone on the development of embryonic neural stem/progenitor cells (NSCs), and the mechanisms underlying these effects. Previous studies indicate that STAT3 plays a crucial role in determining NSC fate during neurodevelopment. In this study, we investigated the effects of a supraphysiological dose of 3,5,3'-L-triiodothyronine (T3) on the proliferation and maintenance of NSCs derived from embryonic day 13.5 mouse neocortex, and the involvement of STAT3 in this process. Our results suggest that excess T3 treatment inhibits NSC proliferation and maintenance. T3 decreased tyrosine phosphorylation of JAK1, JAK2 and STAT3, and subsequently inhibited STAT3-DNA binding activity. Furthermore, proliferation and maintenance of NSCs were decreased by inhibitors of JAKs and STAT3, indicating that the STAT3 signalling pathway is involved in the process of NSC proliferation and maintenance. Taken together, these results suggest that the STAT3 signalling pathway is involved in the process of T3-induced inhibition of embryonic NSC proliferation and maintenance. These findings provide data for understanding the effects of hyperthyroidism during pregnancy on fetal brain development, and the mechanisms underlying these effects.

Pituitary and Peripheral Hormone Responses to T3 Administration During Antarctic Residence

DTIC Science & Technology

1988-06-01

CA, and McMurdo, Antarctica. The basal diet consisted of 2,000-2,500 kcalories (kcal), with -40% as carbohydrate, 35% as protein, and 12.5, 12.5, 12.5...and Diet ranges may have precluded us from detecting basal non- Even though the amount of consumed calories in- stimulated differences. Others have... hypocaloric feed- exposure. MOG, microgram. * P < 0.05 compared with warm control ing cannot account for our findings because serum T 3 in climate values

Placental Transfer of Perfluoroalkyl Substances and Associations with Thyroid Hormones: Beijing Prenatal Exposure Study

NASA Astrophysics Data System (ADS)

Yang, Lin; Li, Jingguang; Lai, Jianqiang; Luan, Hemi; Cai, Zongwei; Wang, Yibaina; Zhao, Yunfeng; Wu, Yongning

2016-02-01

Perfluoroalkyl substances (PFASs) have been detected in wildlife and human samples worldwide. Toxicology research showed that PFASs could interfere with thyroid hormone homeostasis. In this study, eight PFASs, fifteen PFAS precursors and five thyroid hormones were analyzed in 157 paired maternal and cord serum samples collected in Beijing around delivery. Seven PFASs and two precursors were detected in both maternal and cord sera with significant maternal-fetal correlations (r = 0.336 to 0.806, all P < 0.001). The median ratios of major PFASs concentrations in fetal versus maternal serum were from 0.25:1 (perfluorodecanoic acid, PFDA) to 0.65:1 (perfluorooctanoic acid, PFOA). Spearman partial correlation test showed that maternal thyroid stimulating hormone (TSH) was negatively correlated with most maternal PFASs (r = -0.261 to -0.170, all P < 0.05). Maternal triiodothyronin (T3) and free T3 (FT3) showed negative correlations with most fetal PFASs (r = -0.229 to -0.165 for T3; r = -0.293 to -0.169 for FT3, all P < 0.05). Our results suggest prenatal exposure of fetus to PFASs and potential associations between PFASs and thyroid hormone homeostasis in humans.

The timecourse of apoptotic cell death during postnatal remodeling of the mouse cochlea and its premature onset by triiodothyronine (T3).

PubMed

Peeters, R P; Ng, L; Ma, M; Forrest, D

2015-05-15

Apoptosis underlies various forms of tissue remodeling during development. Prior to the onset of hearing, thyroid hormone (T3) promotes cochlear remodeling, which involves regression of the greater epithelial ridge (GER), a transient structure of columnar cells adjacent to the mechanosensory hair cells. We investigated the timecourse of apoptosis in the GER and the influence of ectopic T3 on apoptosis. In saline-treated mice, activated caspase 3-positive cells were detected in the GER between postnatal days 7 and 13 and appeared progressively along the cochlear duct from base to apex over developmental time. T3 given on P0 and P1 advanced the overall program of apoptosis and remodeling by ~4 days. Thyroid hormone receptor β was required for these actions, suggesting a receptor-mediated process of initiation of apoptosis. Finally, T3 given only at P0 or P1 resulted in deafness in adult mice, thus revealing a transient period of susceptibility to long-term damage in the neonatal auditory system. Published by Elsevier Ireland Ltd.

Thyroid hormones and changes in body weight and metabolic parameters in response to weight loss diets: the POUNDS LOST trial.

PubMed

Liu, G; Liang, L; Bray, G A; Qi, L; Hu, F B; Rood, J; Sacks, F M; Sun, Q

2017-06-01

The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown. To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight loss setting. Data analysis was conducted among 569 overweight and obese participants aged 30-70 years with normal thyroid function participating in the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine (T3), free thyroxine (T4), total T3, total T4 and thyroid-stimulating hormone (TSH)), anthropometric measurements and biochemical parameters were assessed at baseline, 6 months and 24 months. Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6 to 24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss±s.e. was -3.87±0.9 vs -5.39±0.9 kg for free T3 (P trend =0.02) and -4.09±0.9 vs -5.88±0.9 kg for free T4 (P trend =0.004). The thyroid hormones did not predict weight regain in 6-24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides and leptin

Thyroid Hormones and Changes in Body Weight and Metabolic Parameters in Response to Weight-Loss Diets: The POUNDS LOST Trial

PubMed Central

Liu, Gang; Liang, Liming; Bray, George A.; Qi, Lu; Hu, Frank B.; Rood, Jennifer; Sacks, Frank M.; Sun, Qi

2017-01-01

Background The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown. Objectives To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting. Subjects/Methods Data analysis was conducted among 569 overweight and obese participants aged 30–70 years with normal thyroid function participating in the 2-year POUNDS LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine [T3], free thyroxine [T4], total T3, total T4, and thyroid stimulating hormone [TSH]), anthropometric measurements, and biochemical parameters were assessed at baseline, 6 months, and 24 months. Results Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6–24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index, and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss ± standard error was −3.87±0.9 vs −5.39±0.9 kg for free T3 (P trend=0.02) and −4.09±0.9 vs −5.88±0.9 kg for free T4 (P trend=0.004). The thyroid hormones did not predict weight regain in 6–24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides

Effects of Steroidal Antiandrogen or 5-alpha-reductase Inhibitor on Prostate Tissue Hormone Content.

PubMed

Shibata, Yasuhiro; Arai, Seiji; Miyazawa, Yoshiyuki; Shuto, Takahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Ito, Kazuto; Suzuki, Kazuhiro

2017-05-01

The effects of a steroidal antiandrogen (AA) and 5-alpha-reductase inhibitor (5ARI) on prostate tissue hormone content and metabolism are not fully elucidated. The objective of this study is to investigate the hormone content and metabolism of the prostate tissues of patients treated with AA or 5ARI using the ultra-sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Thirty-nine patients with benign prostatic hyperplasia (BPH) undergoing transurethral surgery were included. Serum and prostate tissue hormone and prostate tissue hormone metabolism analyses were performed using LC-MS/MS after 1 month of treatment with chlormadinone acetate (CMA; steroidal AA, 50 mg/day) or dutasteride (DUTA; dual 5ARI, 0.5 mg/day). Serum testosterone (T), dihydrotestosterone (DHT), and adrenal androgen levels were lower in the CMA group than the control group. Prostate tissue T and DHT levels were also lower in the CMA group than the control group. In the DUTA group, only serum and prostate DHT concentrations were reduced compared to the control group; in contrast, those of other hormones, especially T and 4-androstene-3,17-dione in the prostate tissue, showed marked elevations up to 70.4- and 11.4-fold normal levels, respectively. Moreover, the hormone metabolism assay confirmed that the conversion of T to DHT was significantly suppressed while that of T to 4-androstene-3,17-dione was significantly accelerated in the prostate tissue of DUTA-treated patients. Although treatment with AA and 5ARI show similar clinical outcomes, their effect on tissue hormone content and metabolism varied greatly. Prostate 77: 672-680, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

CIRCULATING CONCENTRATIONS OF THYROID HORMONE IN BELUGA WHALES (DELPHINAPTERUS LEUCAS): INFLUENCE OF AGE, SEX, AND SEASON.

PubMed

Flower, Jennifer E; Allender, Matthew C; Giovanelli, Richard P; Summers, Sandra D; Spoon, Tracey R; St Leger, Judy A; Goertz, Caroline E C; Dunn, J Lawrence; Romano, Tracy A; Hobbs, Roderick C; Tuttle, Allison D

2015-09-01

Thyroid hormones play a critical physiologic role in regulating protein synthesis, growth, and metabolism. To date, because no published compilation of baseline values for thyroid hormones in beluga whales (Delphinapterus leucas) exists, assessment of thyroid hormone concentrations in this species has been underused in clinical settings. The purpose of this study was to document the concentrations of total thyroxine (tT4) and total triiodothyronine (tT3) in healthy aquarium-maintained and free-ranging beluga whales and to determine the influence of age, sex, and season on the thyroid hormone concentrations. Archived serum samples were collected from healthy aquarium-maintained (n=43) and free-ranging (n=39) belugas, and serum tT4 and tT3 were measured using chemiluminescence immunoassay. The mean tT4 concentration in aquarium-maintained belugas was 5.67±1.43 μg/dl and the mean tT3 concentration was 70.72±2.37 ng/dl. Sex comparisons showed that aquarium-maintained males had significantly greater tT4 and tT3 (9.70±4.48 μg/dl and 92.65±30.55 ng/dl, respectively) than females (7.18±2.82 μg/dl and 77.95±20.37 ng/dl) (P=0.004 and P=0.013). Age comparisons showed that aquarium-maintained whales aged 1-5 yr had the highest concentrations of tT4 and tT3 (8.17±0.17 μg/dl and 105.46±1.98 ng/dl, respectively) (P=0.002 and P<0.001). tT4 concentrations differed significantly between seasons, with concentrations in winter (4.59±1.09 μg/dl) being significantly decreased compared with spring (P=0.009), summer (P<0.0001), and fall (P<0.0001) concentrations. There was a significant difference in tT4 and tT3 concentrations between aquarium-maintained whales (5.67±1.43 μg/dl and 70.72±15.57 ng/dl, respectively) and free-ranging whales (11.71±3.36 μg/dl and 103.38±26.45 ng/dl) (P<0.0001 and P<0.001). Clinicians should consider biologic and environmental influences (age, sex, and season) for a more accurate interpretation of thyroid hormone concentrations in belugas

Molecular characterization of human thyroid hormone receptor β isoform 4.

PubMed

Moriyama, Kenji; Yamamoto, Hiroyuki; Futawaka, Kumi; Atake, Asami; Kasahara, Masato; Tagami, Tetsuya

2016-01-01

Thyroid hormone exerts a pleiotropic effect on development, differentiation, and metabolism through thyroid hormone receptor (TR). A novel thyroid hormone receptor β isoform (TRβ4) was cloned using PCR from a human pituitary cDNA library as a template. We report here the characterization of TRβ4 from a molecular basis. Temporal expression of TRβ4 during the fetal period is abundant in the brain and kidney, comparable with the adult pattern. Western blot analysis revealed that TRs are ubiquitination labile proteins, while TRβ1 is potentially stable. TRβ1, peroxisome proliferator-activated receptors (PPAR), and vitamin D receptor (VDR), which belong to class II transcription factors that function via the formation of heterodimeric complexes with retinoid X receptor (RXR), were suppressed by TRβ4 in a dose-dependent manner. Thus, TRβ4 exhibits ligand-independent transcriptional silencing, possibly as a substitute for dimerized RXR. In this study, TRβ1 and TRβ4 transcripts were detected in several cell lines. Quantitative RT-PCR assay showed that the expression of TRβ4 in human embryonic carcinoma cells of the testis was suppressed by sex hormone in a reciprocal manner to TRβ1. In contrast, TRβ4 was expressed under a high dose of triiodothyronine (T3) in a reciprocal manner to TRβ1. Finally, in transiently transfected NIH-3T3 cells, green fluorescence protein (GFP)-tagged TRβ4 was mostly nuclear in both the absence and the presence of T3. By mutating defined regions of both TRβs, we found that both TRβ1 and TRβ4 had altered nuclear/cytoplasmic distribution as compared with wild-type, and different to T3 and the nuclear receptor corepressor (NCoR). Thus, site-specific DNA binding is not essential for maintaining TRβs within the nucleus.

Relationship of long-term macronutrients intake on anabolic-catabolic hormones in female elite volleyball players.

PubMed

Mielgo Ayuso, Juan; Zourdos, Michael C; Urdampilleta, Aritz; Calleja González, Julio; Seco, Jesús; Córdova, Alfredo

2017-10-24

Specific macronutrient distribution and training can alter acute and chronic hormone behavior and, subsequently, sport performance. The main aim was to examine relationships between dietary intake and anabolic/catabolic hormone response in elite female volleyball players during a 29-week season. Twenty-two elite female volleyballers (26.4 ± 5.6 years; 178 ± 9 cm; 67.1 ± 7.5 kg) had dietary intake (seven-day dietary recall and food frequency questionnaire), blood concentration of anabolic/catabolic hormones concentration, physical performance, and body composition assessed at four time points: a) T1: baseline/pre-testing; b) T2: eleven weeks after T1; c) T3: ten weeks after T2; and d) T4: eight weeks after T3. Hormones evaluated were: total testosterone (TT), free testosterone (FT) adrenocorticotropic hormone (ACTH), and cortisol (C), along with hormone ratios. Positive correlations were observed between carbohydrate/protein ratio with ΔFT (r = 0.955; p < 0.001), ΔTT/C ratio (r = 0.638; p = 0.047), and ΔFT/C ratio (r = 0.909; p < 0.001). Significant and negative correlations were found between protein intake with ΔTT (r = -0.670; p = 0.034), and FT (r = -0.743; p < 0.001), carbohydrate intake and ΔACTH (r = -0.658; p = 0.006). No relationships were observed regarding Δcortisol. On the other hand, there was no change (p > 0.05) in body mass or body mass index at any time point, and the sum of six skinfolds improved (p < 0.05) from T1 (86.5 ± 6.9 mm) to T4 (75.2 ± 5.6 mm) as did muscle mass (T1: 28.9 ± 0.7 kg vsT4: 30.1 ± 0.8 kg). Vertical jump, spike-jump and speed improved (p < 0.05) from T1 to T4. A high carbohydrate/protein ratio was associated with positive changes in anabolism, while high protein and low carbohydrates (CHO) were associated with an attenuated anabolic response.

The relationship between sex hormones, sex hormone binding globulin and peripheral artery disease in older persons.

PubMed

Maggio, M; Cattabiani, C; Lauretani, F; Artoni, A; Bandinelli, S; Schiavi, G; Vignali, A; Volpi, R; Ceresini, G; Lippi, G; Aloe, R; De Vita, F; Giallauria, F; McDermott, M M; Ferrucci, L; Ceda, G P

2012-12-01

The prevalence of peripheral artery disease (PAD) increases with aging and is higher in persons with metabolic syndrome and diabetes. PAD is associated with adverse outcomes, including frailty and disability. The protective effect of testosterone and sex hormone binding globulin (SHBG) for diabetes in men suggests that the biological activity of sex hormones may affect PAD, especially in older populations. Nine hundred and twenty-one elderly subjects with data on SHBG, testosterone (T), estradiol (E2) were selected from InCHIANTI study. PAD was defined as an Ankle-Brachial Index (ABI) < 0.90. Logistic regression models adjusted for age (Model 1), age, BMI, insulin, interleukin-6, physical activity, smoking, chronic diseases including metabolic syndrome (Model 2), and a final model including also sex hormones (Model 3) were performed to test the relationship between SHBG, sex hormones and PAD. The mean age (±SD) of the 419 men and 502 women was 75.0 ± 6.8 years. Sixty two participants (41 men, 21 women) had ABI < 0.90. Men with PAD had SHBG levels lower than men without PAD (p = 0.03). SHBG was negatively and independently associated with PAD in men (p = 0.028) but not in women. The relationship was however attenuated after adjusting for sex hormones (p = 0.07). The E2 was not significantly associated with PAD in both men and women. In women, but not in men, T was positively associated with PAD, even after adjusting for multiple confounders, including E2 (p = 0.01). Low SHBG and high T levels are significantly and independently associated with the presence of PAD in older men and women, respectively. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Circulating thyroid hormones and associated metabolites in white whales (Delphinapterus leucas) determined using isotope-dilution mass spectrometry.

PubMed

Hansen, Martin; Villanger, Gro D; Bechshoft, Thea; Levin, Milton; Routti, Heli; Kovacs, Kit M; Lydersen, Christian

2017-07-01

Blood was sampled from nine free-ranging white whales (beluga whale, Delphinapterus leucas) from Svalbard, Norway during the summers of 2013 and 2014. Total concentrations of eleven thyroid hormones and metabolites were measured in serum using a novel liquid chromatography tandem mass spectrometry analytical method. Measurements of these compounds in plasma gave the same results as in serum. The three hormones found in highest concentrations were 3,3',5-triiodothyronine (T 3 ), 3,3',5'-triiodothyronine (rT 3 ) and thyroxine (T 4 ). Traces of associated metabolites were also found. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of 17β-hydroxysteroid dehydrogenase type 3 as a target in hormone-dependent prostate cancer therapy.

PubMed

Ning, Xiaohui; Yang, Yan; Deng, Hong; Zhang, Qihao; Huang, Yadong; Su, Zhijian; Fu, Yongmei; Xiang, Qi; Zhang, Shu

2017-05-01

17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) is expressed almost exclusively in the testes and specifically converts the weak androgenic androstenedione to active testosterone (T) in the presence of NADPH. Additionally, studies have demonstrated that 17β-HSD3 is over-expressed in hormone-dependent prostate cancer. T, which interacts with the androgen receptor (AR), eventually stimulates the growth of prostate cancer cells. Defects in T synthesis or action impair the development of the male phenotype during embryogenesis and cause the autosomal recessive disorder male pseudohermaphroditism. Affected individuals are often born with female-appearing external genitalia and are reared as females. Since 17β-HSD3 plays a central role in T production, it has been recognized as a promising therapeutic target to reduce the circulating level of androgens and to suppress androgen-sensitive tumor proliferation. In recent decades, improvements have been made in the development of 17β-HSD3 inhibitors. Herein, we give an overview of the main structure and function of human 17β-HSD3 and summarize steroidal and non-steroidal inhibitors of 17β-HSD3, which can be a potential target for prostate cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women.

PubMed

Shifren, Jan L; Desindes, Sophie; McIlwain, Marilyn; Doros, Gheorghe; Mazer, Norman A

2007-01-01

To compare the changes induced by oral versus transdermal estrogen therapy on the total and free serum concentrations of testosterone (T), thyroxine (T4), and cortisol (C) and the concentrations of their serum binding globulins sex hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin in naturally menopausal women. Randomized, open-label, crossover. Interventions included a 6-week withdrawal from previous hormone therapy (baseline), followed in randomized order by 12 weeks of oral conjugated equine estrogens (CEE) (0.625 mg/d) and 12 weeks of transdermal estradiol (TD E2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both transdermal estrogen therapy regimens. Twenty-seven women were enrolled in the study, and 25 completed both treatment periods. The mean(SD) percentage changes from baseline of sex hormone-binding globulin, total T, and free T with oral CEE were +132.1% (74.5%), +16.4% (43.8%), and -32.7% (25.9%), respectively, versus +12.0% (25.1%), +1.2% (43.7%), and +1.0% (45.0%) with TD E2. The mean (SD) percentage changes of thyroxine-binding globulin, total T4, and free T4 with oral CEE were +39.9% (20.1%), +28.4% (29.2%), and -10.4% (22.3%), respectively, versus +0.4% (11.1%), -0.7% (16.5%), and +0.2% (26.6%) with TD E2. The mean (SD) percentage changes of cortisol-binding globulin, total C, and free C with oral CEE were +18.0% (19.5%), +29.2% (46.3%), and +50.4% (126.5%), respectively, versus -2.2% (11.3%), -6.7% (30.8%), and +1.8% (77.1%) with TD E2. Concentrations of all hormones and binding globulins were significantly different (P < or = 0.003) during administration of oral versus transdermal estrogen therapy, except for free T4 and free C. Compared with oral CEE, TD E2 exerts minimal effects on the total and free concentrations of T, T4, and C and their binding proteins.

Hormonal Regulation and Distinct Functions of Semaphorin-3B and Semaphorin-3F in Ovarian Cancer

PubMed Central

Joseph, Doina; Ho, Shuk-Mei; Syed, Viqar

2009-01-01

Semaphorins comprise a family of molecules that influence neuronal growth and guidance. Class-3 semaphorins, semaphorin-3B (SEMA3B) and semaphorin-3F (SEMA3F) illustrate their effects by forming a complex with neuropilins (NP-1 or NP-2) and plexins. We examined the status and regulation of semaphorins and their receptors in human ovarian cancer cells. A significantly reduced expression of SEMA3B (83 kD), SEMA3F (90 kD), and plexin-A3 was observed in ovarian cancer (OVCA) cell lines when compared to normal human ovarian surface epithelial (HOSE) cells. The expression of NP-1, NP-2 and plexin-A1 was not altered in HOSE and OVCA cells. The decreased expression of SEMA3B, SEMA3F, and plexin-A3 was confirmed in stage 3 ovarian tumors. Treatment of OVCA cells with luteinizing hormone, follicle-stimulating hormone, and estrogen induced a significant upregulation of SEMA3B, whereas SEMA3F was upregulated only by estrogen. Co-treatment of cell lines with a hormone and its specific antagonist blocked the effect of the hormone. Ectopic expression of SEMA3B or SEMA3F reduced soft-agar colony formation, adhesion, and cell invasion of OVCA cell cultures. Forced expression of SEMA3B, but not SEMA3F, inhibited viability of OVCA cells. Overexpression of SEMA3B and SEMA3F reduced focal adhesion kinase (FAK) phosphorylation and matrix metalloproteinase (MMP)-2 and -9 expression in OVCA cells. Forced expression of SEMA3F, but not SEMA3B in OVCA cells, significantly inhibited endothelial cell tube formation. Collectively, our results suggest loss of SEMA3 expression could be a hallmark of cancer progression. Furthermore, gonadotropin- and/or estrogen-mediated maintenance of SEMA3 expression could control ovarian cancer angiogenesis and metastasis. PMID:20124444

Thyroid hormone receptor inhibits hepatoma cell migration through transcriptional activation of Dickkopf 4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chi, Hsiang-Cheng; Liao, Chen-Hsin; Huang, Ya-Hui

Highlights: •T{sub 3} affects DKK4 mRNA and protein expression in HepG2-TR cells. •Regulation of DKK4 by T{sub 3} is at transcriptional level. •DKK4 overexpression suppresses hepatoma cell metastasis. -- Abstract: Triiodothyronine (T{sub 3}) is a potent form of thyroid hormone mediates several physiological processes including cellular growth, development, and differentiation via binding to the nuclear thyroid hormone receptor (TR). Recent studies have demonstrated critical roles of T{sub 3}/TR in tumor progression. Moreover, long-term hypothyroidism appears to be associated with the incidence of human hepatocellular carcinoma (HCC), independent of other major HCC risk factors. Dickkopf (DKK) 4, a secreted protein thatmore » antagonizes the canonical Wnt signaling pathway, is induced by T{sub 3} at both mRNA and protein levels in HCC cell lines. However, the mechanism underlying T{sub 3}-mediated regulation of DKK4 remains unknown. In the present study, the 5′ promoter region of DKK4 was serially deleted, and the reporter assay performed to localize the T{sub 3} response element (TRE). Consequently, we identified an atypical direct repeat TRE between nucleotides −1645 and −1629 conferring T{sub 3} responsiveness to the DKK4 gene. This region was further validated using chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA). Stable DKK4 overexpression in SK-Hep-1 cells suppressed cell invasion and metastatic potential, both in vivo andin vitro, via reduction of matrix metalloproteinase-2 (MMP-2) expression. Our findings collectively suggest that DKK4 upregulated by T{sub 3}/TR antagonizes the Wnt signal pathway to suppress tumor cell progression, thus providing new insights into the molecular mechanism underlying thyroid hormone activity in HCC.« less

Effects of recombinant human growth hormone in the treatment of dwarfism and relationship between IGF-1, IGFBP-3 and thyroid hormone

PubMed Central

Ren, Shanxiang; Nie, Yuxiang; Wang, Aihong

2016-01-01

The effects of recombinant human growth hormone (rhGH) in the treatment of dwarfism and the relationship between insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3 and thyroid hormone were examined in the present study. For this purpose, 66 patients diagnosed with dwarfism were selected retrospectively, with 36 cases of growth hormone deficiency (GHD) and 30 cases of idiopathic short stature (ISS). The therapeutic dose of GHD 0.10 IU/kg·day and ISS 0.15 IU/kg·day were injected subcutaneously every night before sleep until adulthood. The average follow-up was 5 years, and the results were evaluated and measured every 3 months, including height, BA, secondary test of growth hormone (GH peak), IGF-1, IGFBP-3 and thyroid hormone (FT3, FT4 and TSH). After treatment, the height, BA, GH peak, IGF-A and IGFBP-3 of the GHD group were all increased, and the differences were statistically significant (P<0.05), while FT3, FT4 and TSH had no significant change (P<0.05). The height and BA increased and the differences were statistically significant (P<0.05). The indexes of the ISS group were not statistically significant (P>0.05). The results of the Pearson-related analysis suggested that GH peak of the GHD group, IGF-1 and IGFBP-3 were positively associated with height (P<0.05), and had no relationship with BA (P<0.05). None of the above indexes of the ISS group had an obvious correlation with height and BA (P>0.05). rhGH was effective for GHD and ISS, with the GHD effect being positively associated with the GH peak, IGF-1 and IGFBP-3. ISS had no obvious relationship with GH peak, IGF-1 and IGFBP-3 although other influencing factors may be involved. PMID:28105090

Effects of recombinant human growth hormone in the treatment of dwarfism and relationship between IGF-1, IGFBP-3 and thyroid hormone.

PubMed

Ren, Shanxiang; Nie, Yuxiang; Wang, Aihong

2016-12-01

The effects of recombinant human growth hormone (rhGH) in the treatment of dwarfism and the relationship between insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3 and thyroid hormone were examined in the present study. For this purpose, 66 patients diagnosed with dwarfism were selected retrospectively, with 36 cases of growth hormone deficiency (GHD) and 30 cases of idiopathic short stature (ISS). The therapeutic dose of GHD 0.10 IU/kg·day and ISS 0.15 IU/kg·day were injected subcutaneously every night before sleep until adulthood. The average follow-up was 5 years, and the results were evaluated and measured every 3 months, including height, BA, secondary test of growth hormone (GH peak), IGF-1, IGFBP-3 and thyroid hormone (FT3, FT4 and TSH). After treatment, the height, BA, GH peak, IGF-A and IGFBP-3 of the GHD group were all increased, and the differences were statistically significant (P<0.05), while FT3, FT4 and TSH had no significant change (P<0.05). The height and BA increased and the differences were statistically significant (P<0.05). The indexes of the ISS group were not statistically significant (P>0.05). The results of the Pearson-related analysis suggested that GH peak of the GHD group, IGF-1 and IGFBP-3 were positively associated with height (P<0.05), and had no relationship with BA (P<0.05). None of the above indexes of the ISS group had an obvious correlation with height and BA (P>0.05). rhGH was effective for GHD and ISS, with the GHD effect being positively associated with the GH peak, IGF-1 and IGFBP-3. ISS had no obvious relationship with GH peak, IGF-1 and IGFBP-3 although other influencing factors may be involved.

Steroid hormonal bioactivities, culprit natural and synthetic hormones and other emerging contaminants in waste water measured using bioassays and UPLC-tQ-MS.

PubMed

Houtman, Corine J; Ten Broek, Rob; Brouwer, Abraham

2018-07-15

Emission of compounds with biological activities from waste water treatment plant (WWTP) effluents into surface waters is a topic of concern for ecology and drinking water quality. We investigated the occurrence of hormone-like activities in waste water sample extracts from four Dutch WWTPs and pursued to identify compounds responsible for them. To this aim, in vitro reporter gene bioassays for androgenic, anti-androgenic, estrogenic, glucocorticoid and progestogenic activity and a UPLC-tQ-MS target analysis method for 25 steroid hormones used in high volumes in pharmacy were applied. Principal component analysis of the data was performed to further characterize the detected activities and compounds. All five types of activities tested were observed in the WWTP samples. Androgenic and estrogenic activities were almost completely removed during WW treatment, anti-androgenic activity was only found in treated WW. Glucocorticoid and progestogenic activities persisted throughout the treatment. The androgenic activity in both influent could predominantly be attributed to the presence of androstenedione and testosterone. Anti-androgenic activity was explained by the presence of cyproterone acetate. The glucocorticoid activity in influent was fully explained by prednicarbate, triamcinolone acetonide, dexamethasone and amcinonide. In effluent however, detected hormones could only explain 10-32% of the activity, indicating the presence of unknown glucocorticoids or their metabolites in effluent. Progesterone and levonorgestrel could explain the observed progestogenic activity. The principle component analysis confirmed the way in which hormones fit in the spectrum of other emerging contaminants concerning occurrence and fate in WWTPs. Copyright © 2018 Elsevier B.V. All rights reserved.

Molecular mechanism of 9-cis-retinoic acid inhibition of adipogenesis in 3T3-L1 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sagara, Chiaki; Takahashi, Katsuhiko; Kagechika, Hiroyuki

2013-03-29

Highlights: ► We examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1. ► 9-cis-RA inhibited lipid accumulation in adipogenetically-induced 3T3-L1 cells. ► A RXR pan-antagonist suppressed the inhibitory effects of 9-cis-RA on adipogenesis. ► This antagonist had no effects on RXRα and PPARγ levels in 9-cis-RA-treated cells. ► 9-cis-RA-induced decrease in both RXRα and PPARγ was independent of RXR activation. -- Abstract: Retinoic acid (RA) signaling is mediated by specific nuclear hormone receptors. Here we examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1 cells. 9-cis-RA inhibits the lipid accumulation of adipogenetically induced 3T3-L1 cells. Themore » complex of retinoid X receptor α (RXRα) with peroxisome proliferator-activated receptor γ (PPARγ) is a major transcription factor in the process of adipogenesis, and the levels of these molecules were decreased by 9-cis-RA treatment. A RXR pan-antagonist suppressed 9-cis-RA’s inhibitory effects on adipogenesis, but not on the intracellular levels of both RXRα and PPARγ. These results suggest that 9-cis-RA could inhibit adipogenesis by activating RXR, and decrease both RXR and PPARγs levels in a RXR activation-independent manner.« less

Musculo-skeletal pain, psychological distress, and hormones during the menopausal transition.

PubMed

Finset, Arnstein; Øverlie, Inger; Holte, Arne

2004-01-01

To investigate the relationship between sex hormones (estradiol, testosterone, androstendione, DHEA-S) and prolactin on one hand and musculo-skeletal pain and psychological distress on the other during the menopausal transition. Fifty-seven regularly menstruating women, who were studied over five consecutive years, who reached menopause before the fifth assessment, and did not use hormone replacement therapy were included in the study. Hormones were sampled and a questionnaire including questions on psychological distress and musculo-skeletal pain were administered at the five points of assessment. Data on last year before menopause (T1), first (T2) and second (T3) year after menopause are reported. DHEA-S, but neither testosterone nor androstendione, was inversely related to distress and pain. Pain contributed to the variance of DHEA-S over the menopausal transition, whereas DHEA-S levels did not predict pain or distress when baseline levels were controlled for. Prolactin was at T1 and T2 positively associated with distress and at T2 positively associated with musculo-skeletal pain. Musculo-skeletal pain pre-menopause was significantly related to estradiol. DHEA-S was negatively associated, and prolactin positively associated with musculo-skeletal pain and psychological distress. Whereas post-menopause DHEA-S levels were influenced by pain scores, no significant effect of pre-menopause hormones on post-menopause pain and distress was found.

Offspring sex in a TSD gecko correlates with an interaction between incubation temperature and yolk steroid hormones

NASA Astrophysics Data System (ADS)

Ding, Guo-Hua; Yang, Jing; Wang, Jin; Ji, Xiang

2012-12-01

We incubated eggs of the Japanese gecko Gekko japonicus at three temperatures, and measured yolk testosterone (T) and 17β-estradiol (E2) levels at three time points in embryonic development (oviposition, 1/3 of incubation, and 2/3 of incubation), to examine whether maternal influence on offspring sex via yolk steroid hormone deposition is significant in the species. Eggs incubated at 24 °C and 32 °C produced mostly females, and eggs incubated at 28 °C almost a 50:50 sex ratio of hatchlings. Female-producing eggs were larger than male-producing eggs. Clutches in which eggs were incubated at the same temperature produced mostly same-sex siblings. Yolk T level at laying was negatively related to eggs mass, and yolk E2/T ratio was positively related to egg mass. Results of two-way ANOVA with incubation temperature and stage as the factors show that: yolk E2 level was higher at 32 °C than at 24 °C; yolk T level was higher, whereas yolk E2/T ratio was smaller, at 28 °C than at 24 °C; yolk E2 and T levels were higher at 2/3 than at 1/3 of incubation. Our data in G. japonucus show that: (1) maternal influence on offspring sex via yolk steroid hormone deposition is significant; (2) incubation temperature affects the dynamics of developmental changes in yolk steroid hormones; (3) influences of yolk steroid hormones on offspring sex are secondary relative to incubation temperature effects; and (4) offspring sex correlates with an interaction between incubation temperature and yolk steroid hormones.

Offspring sex in a TSD gecko correlates with an interaction between incubation temperature and yolk steroid hormones.

PubMed

Ding, Guo-Hua; Yang, Jing; Wang, Jin; Ji, Xiang

2012-12-01

We incubated eggs of the Japanese gecko Gekko japonicus at three temperatures, and measured yolk testosterone (T) and 17β-estradiol (E2) levels at three time points in embryonic development (oviposition, 1/3 of incubation, and 2/3 of incubation), to examine whether maternal influence on offspring sex via yolk steroid hormone deposition is significant in the species. Eggs incubated at 24 °C and 32 °C produced mostly females, and eggs incubated at 28 °C almost a 50:50 sex ratio of hatchlings. Female-producing eggs were larger than male-producing eggs. Clutches in which eggs were incubated at the same temperature produced mostly same-sex siblings. Yolk T level at laying was negatively related to eggs mass, and yolk E2/T ratio was positively related to egg mass. Results of two-way ANOVA with incubation temperature and stage as the factors show that: yolk E2 level was higher at 32 °C than at 24 °C; yolk T level was higher, whereas yolk E2/T ratio was smaller, at 28 °C than at 24 °C; yolk E2 and T levels were higher at 2/3 than at 1/3 of incubation. Our data in G. japonucus show that: (1) maternal influence on offspring sex via yolk steroid hormone deposition is significant; (2) incubation temperature affects the dynamics of developmental changes in yolk steroid hormones; (3) influences of yolk steroid hormones on offspring sex are secondary relative to incubation temperature effects; and (4) offspring sex correlates with an interaction between incubation temperature and yolk steroid hormones.

Estradiol and corticosterone stimulate the proliferation of a GH cell line, MtT/S: Proliferation of growth hormone cells.

PubMed

Nogami, Haruo; Hiraoka, Yoshiki; Aiso, Sadakazu

2016-08-01

Estrogens are known as a potent growth-stimulator of the anterior pituitary cells such as prolactin cells and somatomammotroph cell lines, while glucocorticoids often inhibit cellular proliferation in the pituitary gland as well as in the extra-pituitary tissues. In this study, the involvement of these steroid hormones in the regulation of proliferation was examined in the MtT/S cells, secreting growth hormone (GH). Effects of estrogens and glucocorticoids were examined in MtT/S cells grown in the medium containing dextran-coated charcoal treated serum. The relative cell density after culture was estimated by the Cell Titer-Glo Luminescent Cell Viability Assay System, and the proliferation rate was determined by the BrdU incorporation method. The mRNA levels were determined by real-time PCR. Estradiol and the specific agonist for both estrogen receptor (ER) α and ERβ stimulated MtT/S growth at a dose dependent manner. The membrane impermeable estrogen, 17β-estradiol-bovine serum albumin conjugate also stimulated the MtT/S proliferation. The effects of all estrogens were inhibited by an estrogen receptor antagonist, ICI182780. Corticosterone stimulated the proliferation of MtT/S cells at doses lower than 10nM without stimulating GH gene transcription, whereas it did not change the proliferation rate at 1μM. The effects of corticosterone were inhibited by glucocorticoid receptor inhibitor, RU486, but not by the mineralocorticoid receptor antagonist, spironolactone. Both estrogens and glucocorticoids were found to stimulate the proliferation of MtT/S, increasing the mRNA expression of cyclins D1, D3, and E. The results suggest that estrogens and glucocorticoids may be involved in the mechanisms responsible for the proliferation of GH cells in the course of pituitary development, to maintain the population of GH cells in the adult pituitary gland, and also in the promotion of GH cell tumors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Purification and characterization of rat liver nuclear thyroid hormone receptors.

PubMed Central

Ichikawa, K; DeGroot, L J

1987-01-01

Nuclear thyroid hormone receptor was purified to 904 pmol of L-3,5,3'-triiodothyronine (T3) binding capacity per mg of protein with 2.5-5.2% recovery by sequentially using hydroxylapatite column chromatography, ammonium sulfate precipitation, Sephadex G-150 gel filtration, DNA-cellulose column chromatography, DEAE-Sephadex column chromatography, and heparin-Sepharose column chromatography. Assuming that one T3 molecule binds to the 49,000-Da unit of the receptor, we reproducibly obtained 6.4-14.7 micrograms of receptor protein with 4.2-4.9% purity from 4-5 kg of rat liver. Elution of receptor from the heparin-Sepharose column was performed using 10 mM pyridoxal 5'-phosphate, which was observed to diminish binding of receptor to heparin-Sepharose or DNA-cellulose. This effect was specific for pyridoxal 5'-phosphate, since related compounds were not effective. Purified receptor bound T3 with high affinity (6.0 X 10(9) liter/mol), and the order of affinity of iodothyronine analogues to purified receptor was identical to that observed with crude receptor preparations [3,5,3'-triiodothyroacetic acid greater than L-T3 greater than D-3,5,3'-triiodothyronine (D-T3) greater than L-thyroxine greater than D-thyroxine]. Purified receptor had a sedimentation coefficient of 3.4 S, Stokes radius of 34 A, and calculated molecular mass of 49,000. Among several bands identified by silver staining after electrophoresis in NaDodSO4/polyacrylamide gels, one 49,000-Da protein showed photoaffinity labeling with [125I]thyroxine that was displaceable with excess unlabeled T3. The tryptic fragment and endogenous proteinase-digested fragment of the affinity-labeled receptor showed saturable binding in 27,000-Da and 36,000-Da peptides, respectively. These molecular masses are in agreement with estimates from gel filtration and gradient sedimentation, indicating that affinity labeling occurred at the hormone binding domain of nuclear thyroid hormone receptor. This procedure reproducibly

In vitro lipid metabolism, growth and metabolic hormone concentrations in hyperthyroid chickens.

PubMed

Rosebrough, R W; McMurtry, J P; Vasilatos-Younken, R

1992-11-01

Indian River male broiler chickens growing from 7 to 28 d of age were fed on diets containing energy:protein values varying from 43 to 106 MJ/kg protein and containing 0 or 1 mg triiodothyronine (T3)/kg diet to study effects on growth, metabolic hormone concentrations and in vitro lipogenesis. In vitro lipid synthesis was determined in liver explants in the presence and absence of ouabain (Na+, K(+)-transporting ATPase (EC 3.6.1.37) inhibitor) to estimate the role of enzyme activity in explants synthesizing lipid. Growth and feed consumption increased (P < 0.01) when the energy:protein value decreased from 106 to 71 MJ/kg protein; however, both variables decreased as the value was further decreased from 53 to 43 MJ/kg protein. Triiodothyronine depressed (P < 0.01) growth, but not food intake. Large energy:protein diets (> 53 MJ/kg protein) and dietary T3 lowered (P < 0.01) plasma growth hormone. Large energy:protein diets (> 53 MJ/kg protein) increased (P < 0.01) lipogenesis, plasma growth hormone (GH) and decreased plasma insulin-like growth factor 1 (IGF-1). Also, T3 decreased plasma GH, IGF-1 in vitro lipogenesis. Ouabain inhibited a greater proportion of in vitro lipogenesis in those explants synthesizing fat at a high rate. Both dietary T3 and in vitro ouabain decrease lipogenesis, but, when combined, the effects are not cumulative.

The impact of thyroid hormones on patients with hepatocellular carcinoma.

PubMed

Pinter, Matthias; Haupt, Lukas; Hucke, Florian; Bota, Simona; Bucsics, Theresa; Trauner, Michael; Peck-Radosavljevic, Markus; Sieghart, Wolfgang

2017-01-01

Hypothyroidism has recently been proposed as predisposing factor for HCC development. However, the role of thyroid hormones (TH) in established HCC is largely unclear. We investigated the impact of TH on clinical characteristics and prognosis of HCC patients. Of 838 patients diagnosed with nonsurgical HCC at the Division of Gastroenterology and Hepatology/Medical University of Vienna between 1992 and 2012, 667 patients fulfilled the inclusion criteria. The associations of thyroid function tests with patient, liver, and tumor characteristics as well as their impact on overall survival (OS) were investigated. Thyroid hormone substitution was more often observed in patients with low thyroid-stimulating hormone (TSH) concentration and in patients with elevated free tetraiodthyronine (fT4). Patients with high TSH (>3.77uU/ml) concentrations had larger tumors, while the opposite was true for patients with low TSH (<0.44uU/ml) concentrations. Subjects with elevated fT4 (>1.66ng/dl) were more likely to have elevated CRP. While TSH was only associated with OS in univariate analysis (≤1.7 vs. >1.7uU/ml, median OS (95%CI), 12.3 (8.9-15.7 months) vs. 7.3 months (5.4-9.2 months); p = 0.003), fT4 (≤1.66 vs. >1.66ng/dl, median OS (95%CI), 10.6 (7.5-13.6 months) vs. 3.3 months (2.2-4.3 months); p = 0.007) remained an independent prognostic factor for OS (HR (95%CI) for fT4>1.66ng/dl, 2.1 (1.3-3.3); p = 0.002) in multivariate analysis. TSH and fT4 were associated with prognostic factors of HCC (i.e., tumor size, CRP level). Elevated fT4 concentrations were independently associated with poor prognosis in HCC. Further studies are needed to characterize the role of TH in HCC in detail.

The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

PubMed

Glynn, Nigel; Kenny, Helena; Quisenberry, Leah; Halsall, David J; Cook, Paul; Kyaw Tun, Tommy; McDermott, John H; Smith, Diarmuid; Thompson, Christopher J; O'Gorman, Donal J; Boelen, Anita; Lado-Abeal, Joaquin; Agha, Amar

2017-05-01

Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement. A prospective, observational study of patients receiving GH replacement as part of routine clinical care. Twenty adult hypopituitary men. Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue. The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy. In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle. © 2016 John Wiley & Sons Ltd.

Decrease in calcitonin and parathyroid hormone mRNA levels and hormone secretion under long-term hypervitaminosis D3 in rats.

PubMed

Fernández-Santos, J M; Utrilla, J C; Conde, E; Hevia, A; Loda, M; Martín-Lacave, I

2001-04-01

In calcium homeostasis, vitamin D3 is a potent serum calcium-raising agent which in vivo regulates both calcitonin (CT) and parathyroid hormone (PTH) gene expression. Serum calcium is the major secretagogue for CT, a hormone product whose biosynthesis is the main biological activity of thyroid C-cells. Taking advantage of this regulatory mechanism, long-term vitamin D3-induced hypercalcemia has been extensively used as a model to produce hyperactivation, hyperplasia and even proliferative lesions of C-cells, supposedly to reduce the sustained high calcium serum concentrations. We have recently demonstrated that CT serum levels did not rise after long-term hypervitaminosis D3. Moreover, C-cells did not have a proliferative response, rather a decrease in CT-producing C-cell number was observed. In order to confirm the inhibitory effect of vitamin D3 on C-cells, Wistar rats were administered vitamin D3 chronically (25,000 IU/d) with or without calcium chloride (CaCl2). Under these long-term vitamin D3-hypercalcemic conditions, calcium, active metabolites of vitamin D3, CT and PTH serum concentrations were determined by RIA; CT and PTH mRNA levels were analysed by Northern blot and in situ hybridization; and, finally, the ultrastructure of calciotrophic hormone-producing cells was analysed by electron microscopy. Our results show, that, in rats, long term administration of vitamin D3 results in a decrease in hormone biosynthetic activities of both PTH and CT-producing cells, albeit at different magnitudes. Based upon these results, we conclude that hypervitaminosis D3-based methods do not stimulate C-cell activity and can not be used to induce proliferative lesions of calcitonin-producing cells.

Mathematical Modeling of the Pituitary–Thyroid Feedback Loop: Role of a TSH-T3-Shunt and Sensitivity Analysis

PubMed Central

Berberich, Julian; Dietrich, Johannes W.; Hoermann, Rudolf; Müller, Matthias A.

2018-01-01

Despite significant progress in assay technology, diagnosis of functional thyroid disorders may still be a challenge, as illustrated by the vague upper limit of the reference range for serum thyrotropin (TSH). Diagnostical problems also apply to subjects affected by syndrome T, i.e., those 10% of hypothyroid patients who continue to suffer from poor quality of life despite normal TSH concentrations under substitution therapy with levothyroxine (L-T4). In this paper, we extend a mathematical model of the pituitary–thyroid feedback loop in order to improve the understanding of thyroid hormone homeostasis. In particular, we incorporate a TSH-T3-shunt inside the thyroid, whose existence has recently been demonstrated in several clinical studies. The resulting extended model shows good accordance with various clinical observations, such as a circadian rhythm in free peripheral triiodothyronine (FT3). Furthermore, we perform a sensitivity analysis of the derived model, revealing the dependence of TSH and hormone concentrations on different system parameters. The results have implications for clinical interpretation of thyroid tests, e.g., in the differential diagnosis of subclinical hypothyroidism. PMID:29619006

Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Role of a TSH-T3-Shunt and Sensitivity Analysis.

PubMed

Berberich, Julian; Dietrich, Johannes W; Hoermann, Rudolf; Müller, Matthias A

2018-01-01

Despite significant progress in assay technology, diagnosis of functional thyroid disorders may still be a challenge, as illustrated by the vague upper limit of the reference range for serum thyrotropin ( TSH ). Diagnostical problems also apply to subjects affected by syndrome T, i.e., those 10% of hypothyroid patients who continue to suffer from poor quality of life despite normal TSH concentrations under substitution therapy with levothyroxine ( L - T 4 ). In this paper, we extend a mathematical model of the pituitary-thyroid feedback loop in order to improve the understanding of thyroid hormone homeostasis. In particular, we incorporate a TSH - T 3 -shunt inside the thyroid, whose existence has recently been demonstrated in several clinical studies. The resulting extended model shows good accordance with various clinical observations, such as a circadian rhythm in free peripheral triiodothyronine ( FT 3 ). Furthermore, we perform a sensitivity analysis of the derived model, revealing the dependence of TSH and hormone concentrations on different system parameters. The results have implications for clinical interpretation of thyroid tests, e.g., in the differential diagnosis of subclinical hypothyroidism.

Rosmarinic acid suppresses adipogenesis, lipolysis in 3T3-L1 adipocytes, lipopolysaccharide-stimulated tumor necrosis factor-α secretion in macrophages, and inflammatory mediators in 3T3-L1 adipocytes

PubMed Central

Rui, Yehua; Tong, Lingxia; Cheng, Jinbo; Wang, Guiping; Qin, Liqiang; Wan, Zhongxiao

2017-01-01

ABSTRACT Background: Rosmarinic acid (RA) is a natural phenol carboxylic acid with many promising biological effects. It may be a suitable candidate for improving obesity-related adipose tissue dysfunction. Objective: We aimed to investigate the therapeutic use of RA as an anti-obesity agent by measuring its effects on adipogenesis, lipolysis, and messenger RNA (mRNA) expression of major adipokines in 3T3-L1 adipocytes; and its effects on lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) secretion in macrophages and inflammatory mediators in 3T3-L1 adipocytes incubated with macrophage-conditioned medium (MCM). Methods: 3T3-L1 preadipocytes were used to explore how RA affects adipogenesis, as well as the involvement of phosphorylated extracellular signal-regulated kinase-1/2 (p-ERK1/2) and mothers against decapentaplegic homolog 3 (p-Smad3). 3T3-L1 preadipocytes were also differentiated into mature adipocytes to explore how RA affects basal and isoproterenol- and forskolin-stimulated lipolysis; and how RA affects key adipokines’ mRNA expression. RAW 264.7 macrophages were stimulated with LPS in the absence or presence of RA to explore RA’s effects on TNF-α secretion. MCM was collected and 3T3-L1 adipocytes were incubated with MCM to explore RA’s effects on interleukin-6 (IL-6), IL-1β, monocyte chemoattractant protein-1 (MCP-1), and RANTES mRNA expression. Results: During the preadipocyte differentiation process, RA suppressed peroxisome proliferator-activated receptor-γ and CCAAT/enhancer binding protein-α, and activated p-ERK1/2 and p-Smad3; inhibition of adipogenesis by RA was partially restored following treatment with p-ERK1/2 and p-Smad3 inhibitors. In mature adipocytes, RA inhibited basal lipolysis; phosphodiesterase-3 inhibitor reversed this. RA also inhibited isoproterenol- and forskolin-stimulated glycerol and free fatty acid release, and the phosphorylation of hormone-sensitive lipase and perilipin. RA had no effects on leptin

Thyroid hormone regulates vitellogenin by inducing estrogen receptor alpha in the goldfish liver.

PubMed

Nelson, Erik R; Habibi, Hamid R

2016-11-15

Vitellogenin (Vtg) is an egg-yolk precursor protein that is synthesized in the liver of oviparous species and taken up from the circulation by the ovary. It is well known that Vtg is induced by circulating estrogens. However, other endocrine factors that regulate the expression of Vtg are less well characterized; factors that might play significant roles, especially in seasonal spawners such as the goldfish which require increased quantities of Vtg for the development of hundreds of follicles. In this regard, thyroid hormones have been shown to cycle with the reproductive season. Therefore, we hypothesized that the thyroid hormones might influence the synthesis of Vtg. Treatment of female goldfish with triiodothyronine (T3) resulted in increased Vtg, an observation that was absent in males. Furthermore, T3 failed to induce Vtg in cultured hepatocytes of either sex. Interestingly however, T3 consistently up-regulated the expression of the estrogen receptor alpha (ERα). The T3 mediated upregulation of ERα requires the presence of both thyroid receptor (TR) α-1 and TRβ. When goldfish or cultured hepatocytes were treated with T3 followed by estradiol, there was a synergistic increase in Vtg, a response which is dependent on the presence of ERα. Therefore, by upregulating ERα, T3 serves to prime the liver to subsequent stimuli from estradiol. This cross-talk likely reveals an important physiologic mechanism by which thyroid hormones, whose circulating levels are high during early gonadal recrudescence, facilitate the production of large amounts of Vtg required for egg development. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Thyroid Hormone in the CNS: Contribution of Neuron-Glia Interaction.

PubMed

Noda, Mami

2018-01-01

The endocrine system and the central nervous system (CNS) are intimately linked. Among hormones closely related to the nervous system, thyroid hormones (THs) are critical for the regulation of development and differentiation of neurons and neuroglia and hence for development and function of the CNS. T3 (3,3',5-triiodothyronine), an active form of TH, is important not only for neuronal development but also for differentiation of astrocytes and oligodendrocytes, and for microglial development. In adult brain, T3 affects glial morphology with sex- and age-dependent manner and therefore may affect their function, leading to influence on neuron-glia interaction. T3 is an important signaling factor that affects microglial functions such as migration and phagocytosis via complex mechanisms. Therefore, dysfunction of THs may impair glial function as well as neuronal function and thus disturb the brain, which may cause mental disorders. Investigations on molecular and cellular basis of hyperthyroidism and hypothyroidism will help us to understand changes in neuron-glia interaction and therefore consequent psychiatric symptoms. © 2018 Elsevier Inc. All rights reserved.

Associations between brominated flame retardants in house dust and hormone levels in men

PubMed Central

Johnson, Paula I.; Stapleton, Heather M.; Mukherjee, Bhramar; Hauser, Russ; Meeker, John D.

2013-01-01

Brominated flame retardants (BFRs) are used in the manufacture of a variety of materials and consumer products in order to meet fire safety standards. BFRs may persist in the environment and have been detected in wildlife, humans and indoor dust and air. Some BFRs have demonstrated endocrine and reproductive effects in animals, but human studies are limited. In this exploratory study, we measured serum hormone levels and flame retardant concentrations [31 polybrominated diphenyl ether (PBDE) congeners and 6 alternate flame retardants] in house dust from men recruited through a US infertility clinic. PBDE congeners in dust were grouped by commercial mixtures (i.e. penta-, octaand deca-BDE). In multivariable linear regression models adjusted by age and body mass index (BMI), significant positive associations were found between house dust concentrations of pentaBDEs and serum levels of free T4, total T3, estradiol, and sex hormone binding globulin (SHBG), along with an inverse association with follicle stimulating hormone (FSH). There were also positive associations of octaBDE concentrations with serum free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH) and testosterone and an inverse association of decaBDE concentrations with testosterone. Hexabromocyclododecane (HBCD) was associated with decreased SHBG and increased free androgen index. Dust concentrations of bis-tribromophenoxyethane (BTBPE) and tetrabromo-diethylhexylphthalate (TBPH) were positively associated with total T3. These findings are consistent with our previous report of associations between PBDEs (BDE 47, 99 and 100) in house dust and hormone levels in men, and further suggest that exposure to contaminants in indoor dust may be leading to endocrine disruption in men. PMID:23333513

Resistance to thyroid hormone due to defective thyroid receptor alpha.

PubMed

Moran, Carla; Chatterjee, Krishna

2015-08-01

Thyroid hormones act via nuclear receptors (TRα1, TRβ1, TRβ2) with differing tissue distribution; the role of α2 protein, derived from the same gene locus as TRα1, is unclear. Resistance to thyroid hormone alpha (RTHα) is characterised by tissue-specific hypothyroidism associated with near-normal thyroid function tests. Clinical features include dysmorphic facies, skeletal dysplasia (macrocephaly, epiphyseal dysgenesis), growth retardation, constipation, dyspraxia and intellectual deficit. Biochemical abnormalities include low/low-normal T4 and high/high-normal T3 concentrations, a subnormal T4/T3 ratio, variably reduced reverse T3, raised muscle creatine kinase and mild anaemia. The disorder is mediated by heterozygous, loss-of-function, mutations involving either TRα1 alone or both TRα1 and α2, with no discernible phenotype attributable to defective α2. Whole exome sequencing and diagnostic biomarkers may enable greater ascertainment of RTHα, which is important as thyroxine therapy reverses some metabolic abnormalities and improves growth, constipation, dyspraxia and wellbeing. The genetic and phenotypic heterogeneity of RTHα and its optimal management remain to be elucidated. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Genomics and CSF analyses implicate thyroid hormone in hippocampal sclerosis of aging

PubMed Central

Nelson, Peter T.; Katsumata, Yuriko; Nho, Kwangsik; Artiushin, Sergey C.; Jicha, Gregory A.; Wang, Wang-Xia; Abner, Erin L.; Saykin, Andrew J.; Kukull, Walter A.; Fardo, David W.

2016-01-01

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer’s neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer’s Coordinating Center/Alzheimer’s Disease Genetic Consortium data; n=2,113, including 241 autopsy-confirmed HS cases). Further, both rs704180 and rs73069071 risk genotypes were associated with widespread brain atrophy visualized by MRI (Alzheimer’s Disease Neuroimaging Initiative data; n=1,239). In human brain samples from the Braineac database, both rs704180 and rs73069071 risk genotypes were associated with variation in expression of ABCC9, a gene which encodes a metabolic sensor protein in astrocytes. The rs73069071 risk genotype was also associated with altered expression of a nearby astrocyte-expressed gene, SLCO1C1. Analyses of human brain gene expression databases indicated that the chromosome 12p12 locus may regulate particular astrocyte-expressed genes induced by the active form of thyroid hormone, triiodothyronine (T3). This is informative biologically because the SLCO1C1 protein transports thyroid hormone into astrocytes from blood. Guided by the genomic data, we tested the hypothesis that altered thyroid hormone levels could be detected in cerebrospinal fluid (CSF) obtained from persons with HS pathology. Total T3 levels in CSF were elevated in HS cases (p<0.04 in two separately analyzed groups), but not in Alzheimer’s disease cases, relative to controls. No change was detected in the serum levels of thyroid hormone (T3 or T4) in a subsample of HS cases prior to death. We conclude that brain thyroid hormone

The immediate and late effects of thyroid hormone (triiodothyronine) on murine coagulation gene transcription.

PubMed

Salloum-Asfar, Salam; Boelen, Anita; Reitsma, Pieter H; van Vlijmen, Bart J M

2015-01-01

Thyroid dysfunction is associated with changes in coagulation. The aim of our study was to gain more insight into the role of thyroid hormone in coagulation control. C57Black/6J mice received a low-iodine diet and drinking water supplemented with perchlorate to suppress endogenous triiodothyronine (T3) and thyroxine (T4) production. Under these conditions, the impact of exogenous T3 on plasma coagulation, and hepatic and vessel-wall-associated coagulation gene transcription was studied in a short- (4 hours) and long-term (14 days) setting. Comparing euthyroid conditions (normal mice), with hypothyroidism (conditions of a shortage of thyroid hormone) and those with replacement by incremental doses of T3, dosages of 0 and 0.5 μg T3/mouse/day were selected to study the impact of T3 on coagulation gene transcription. Under these conditions, a single injection of T3 injection increased strongly hepatic transcript levels of the well-characterized T3-responsive genes deiodinase type 1 (Dio1) and Spot14 within 4 hours. This coincided with significantly reduced mRNA levels of Fgg, Serpinc1, Proc, Proz, and Serpin10, and the reduction of the latter three persisted upon daily treatment with T3 for 14 days. Prolonged T3 treatment induced a significant down-regulation in factor (F) 2, F9 and F10 transcript levels, while F11 and F12 levels increased. Activity levels in plasma largely paralleled these mRNA changes. Thbd transcript levels in the lung (vessel-wall-associated coagulation) were significantly up-regulated after a single T3 injection, and persisted upon prolonged T3 exposure. Two-week T3 administration also resulted in increased Vwf and Tfpi mRNA levels, whereas Tf levels decreased. These data showed that T3 has specific effects on coagulation, with Fgg, Serpinc1, Proc, Proz, Serpin10 and Thbd responding rapidly, making these likely direct thyroid hormone receptor targets. F2, F9, F10, F11, F12, Vwf, Tf and Tfpi are late responding genes and probably indirectly

Associations of serum sex steroid hormones and 5α-androstane-3α,17β-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride

PubMed Central

Kristal, Alan R.; Till, Cathee; Tangen, Catherine M.; Goodman, Phyllis J.; Neuhouser, Marian L.; Stanczyk, Frank Z.; Chu, Lisa W.; Patel, Sherfaraz K.; Thompson, Ian; Reichardt, Juergen K.; Hoque, Ashraful; Platz, Elizabeth A.; Figg, William D.; Van Bokhoven, Adrie; Lippman, Scott M.; Hsing, Ann W

2012-01-01

BACKGROUND Finasteride, an inhibitor of 5 α-reductase (Type II), lowers intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced 5α-androstane-3α,17β-diol glucuronide (3α-dG). It also modestly increases serum testosterone (T), estrone (E1) and estradiol (E2). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk. METHODS In this nested case-control study of men in the finasteride arm of the Prostate Cancer Prevention Trial, sex steroid hormones and sex hormone binding globulin (SHBG) were measured at baseline and approximately 3-years post-treatment in 553 prostate cancer cases and 694 controls. RESULTS Median post-treatment changes in concentrations of 3α-dG, T, E1, and E2 were −73.8%, +10.1%, +11.2%, and +7.5% (all p<0.001), respectively. Neither the pre- nor post-treatment concentrations of 3α-dG, nor its change, were associated with risk. Pre-treatment, high concentrations of E1 and low concentrations of T were associated with increased cancer risk (Odds Ratio[95% CI] quartile 4 vs 1: 1.38[0.99–1.93] ptrend=0.03; 0.64 [0.43–0.93] ptrend=0.07, respectively). Post-treatment, high concentrations of both E1 and E2 and were associated with increased cancer risk (OR[95% CI] quartile 4 vs 1: 1.54[1.09–2.17] ptrend=0.03; 1.49[1.07–2.07] ptrend=0.02, respectively). CONCLUSIONS Among finasteride-treated men, concentrations of 3α-dG were not associated with total or Gleason grades 2–6, 7–10 or 8–10 cancer. High serum estrogens may increase cancer risk when intraprostatic DHT is pharmacologically lowered. IMPACT Low post-treatment serum estrogens may identify men more likely to benefit from use of finasteride to prevent prostate cancer. PMID:22879203

Thyroid hormone levels in the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.

PubMed Central

Tang, W W; Kaptein, E M

1989-01-01

Hypothalamic-pituitary dysfunction and thyroid gland cytomegalovirus inclusions have been described in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). We evaluated 80 patients with AIDS or ARC for the frequency of hypothalamic-pituitary or thyroid gland failure and altered serum thyroid hormone levels due to nonthyroidal disorders. One patient had subclinical hypothyroidism. Of these patients, 60% had low free triiodothyronine (T3) index values and 4% had low free thyroxine (T4) indexes; none of the latter had hypothalamic-pituitary or thyroid gland failure, since all serum cortisol values were greater than or equal to 552 nmol per liter (greater than or equal to 20 micrograms per dl) and all thyrotropin levels were less than or equal to 3 mU per liter (less than or equal to 3 microU per ml), respectively. Those who died had lower total T4 and T3, free T3 index, and albumin levels than those discharged from hospital. Serum total T4 and T3 levels correlated with albumin levels and total T3 with serum sodium levels. Serum total T3 levels best predicted the outcome of the hospital stay (accuracy = 82%). Thus, abnormal serum thyroid hormone levels in AIDS or ARC patients are most frequently due to nonthyroidal disorders, but hypothalamic-pituitary or thyroid gland failure may occur. PMID:2618039

Effects on development, growth responses and thyroid-hormone systems in eyed-eggs and yolk-sac larvae of Atlantic salmon (Salmo salar) continuously exposed to 3,3',4,4'-tetrachlorobiphenyl (PCB-77).

PubMed

Arukwe, Augustine; Olufsen, Marianne; Cicero, Nicola; Hansen, Marianne D

2014-01-01

Thyroid hormones (triiodothyronine, T3; and thyroxine, T4) play significant roles in development, metamorphosis, metabolism, homeostasis, cellular proliferation, and differentiation, for which the effects are mediated through thyroid hormone receptors (TRα and TRβ). Similarly, the insulin-like growth factor (IGF) is involved in growth and development through regulation of somatic growth. This study was designed to examine the effects of the dioxin-like 3,3',4,4'-tetrachlorobiphenyl (PCB-77) on responses related to growth and thyroid hormone system in eyed eggs and yolk-sac larvae of Atlantic salmon. Salmon eggs were continuously exposed to two waterborne concentrations of PCB-77 (1 or 10 ng/L) over a period of 50 d covering hatching and through yolk-sac absorption stages. Sampling was performed regularly throughout the exposure period and at different time intervals. Gene expression patterns were performed on whole-body homogenate at age 500, 548, 632, 674, and 716 dd (dd: day degrees) using quantitative polymerase chain reaction (PCR). Total T3 (TT3) and total T4 (TT4) were measured using radioimmunoassay (RIA). Data showed that 10 ng PCB-77 increased dioiodinase 2 (Dio2) at 500 dd and both PCB-77 concentrations decreased dio2 expression at 548 dd. PCB-77 elevated cellular TT3 at 500 dd and was lowered at 548 dd only at 10 ng. Otherwise, time-related reduction was not affected by PCB-77 exposure as observed for the rest of the exposure period. For TT4, 1 ng PCB-77 produced a rise at 500 dd, and an apparent concentration decrease at 548 dd, before a total inhibition at 632 dd. The IGF-1 and IGF-1R were variably affected by PCB-77. For IGF-2, PCB-77 produced a concentration-dependent increase at 548 dd, and thereafter an elevation (1 ng) and fall (10 ng) at 632 dd. TRβ mRNA demonstrated PCB-77 related increases during the exposure period, and this effect returned to control levels at 716 dd. For TRα, a rise was noted only after exposure to 10 ng PCB-77 at 500 dd

Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin

PubMed Central

Danilovic, Debora Lucia Seguro; Mendes-Correa, Maria Cassia; Chammas, Maria Cristina; Zambrini, Heverton; Marui, Suemi

2011-01-01

OBJECTIVE: To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. INTRODUCTION: Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. METHODS: We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. RESULTS: Of the patients in our study, 54% had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH) levels remained stable. A total of 19% of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16% had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11% remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. DISCUSSION: Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. CONCLUSION: Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels), which occur despite stable free T4 and TSH levels. A thyroid hormonal evaluation

Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin.

PubMed

Danilovic, Debora Lucia Seguro; Mendes-Correa, Maria Cassia; Chammas, Maria Cristina; Zambrini, Heverton; Marui, Suemi

2011-01-01

To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. Of the patients in our study, 54% had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH) levels remained stable. A total of 19% of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16% had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11% remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels), which occur despite stable free T4 and TSH levels. A thyroid hormonal evaluation, including the analysis of the free T4, TSH, and antithyroid

Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure

PubMed Central

Sowa, Jan-Peter; Manka, Paul; Katsounas, Antonios; Syn, Wing-Kin; Führer, Dagmar; Gieseler, Robert K.; Bechmann, Lars P.; Gerken, Guido; Moeller, Lars C.; Canbay, Ali

2015-01-01

Introduction Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF. Methods 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined. Results More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression. Conclusions In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity. PMID:26147961

Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure.

PubMed

Anastasiou, Olympia; Sydor, Svenja; Sowa, Jan-Peter; Manka, Paul; Katsounas, Antonios; Syn, Wing-Kin; Führer, Dagmar; Gieseler, Robert K; Bechmann, Lars P; Gerken, Guido; Moeller, Lars C; Canbay, Ali

2015-01-01

Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF. 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined. More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression. In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity.

Non-invasive measurement of thyroid hormone in feces of a diverse array of avian and mammalian species.

PubMed

Wasser, Samuel K; Azkarate, Jurgi Cristòbal; Booth, Rebecca K; Hayward, Lisa; Hunt, Kathleen; Ayres, Katherine; Vynne, Carly; Gobush, Kathleen; Canales-Espinosa, Domingo; Rodríguez-Luna, Ernesto

2010-08-01

We developed and validated a non-invasive thyroid hormone measure in feces of a diverse array of birds and mammals. An I(131) radiolabel ingestion study in domestic dogs coupled with High Pressure Liquid Chromatography (HPLC) analysis, showed that peak excretion in feces occurred at 24-48h post-ingestion, with I(131)-labelled thyroid hormone metabolites excreted primarily as triiodothyronine (T3) and relatively little thyroxine (T4), at all excretion times examined. The immunoreactive T3 profile across these same HPLC fractions closely corresponded with the I(131) radioactive profile. By contrast, the T4 immunoreactive profile was disproportionately high, suggesting that T4 excretion included a high percentage of T4 stores. We optimized and validated T3 and T4 extraction and assay methods in feces of wild northern spotted owls, African elephants, howler monkeys, caribou, moose, wolf, maned wolf, killer whales and Steller sea lions. We explained 99% of the variance in high and low T3 concentrations derived from species-specific sample pools, after controlling for species and the various extraction methods tested. Fecal T3 reflected nutritional deficits in two male and three female howler monkeys held in captivity for translocation from a highly degraded habitat. Results suggest that thyroid hormone can be accurately and reliably measured in feces, providing important indices for environmental physiology across a diverse array of birds and mammals. Copyright 2010 Elsevier Inc. All rights reserved.

Age-related differences in hormonal and nutritional impact on lean anorexia nervosa bone turnover uncoupling.

PubMed

Galusca, B; Bossu, C; Germain, N; Kadem, M; Frere, D; Lafage-Proust, M H; Lang, F; Estour, B

2006-01-01

In anorexia nervosa (AN) patients osteoporosis occurs within a framework of multiple hormonal abnormalities as a result of bone turnover uncoupling, with decreased bone formation and increased bone resorption. The aim of study was to evaluate the hormonal and nutritional relationships with both of these bone remodeling compartments and their eventual modifications with age. In a cohort of 115 AN patients (mean BMI:14.6 kg/m2) that included 60 mature adolescents (age: 15.5-20 years) and 55 adult women (age: 20-37 years) and in 28 age-matched controls (12 mature adolescents and 16 adults) we assessed: bone markers [serum osteocalcin, skeletal alkaline phosphatase (sALP), C-telopeptide of type I collagen (sCTX) and tartrate-resistant acid phosphatase type 5b (TRAP 5b)], nutritional markers [ body mass index (BMI, fat and lean mass), hormones (free tri-iodothyronine (T3), free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), 17 beta estradiol, free testosterone index (FTI), dehydroepiandrosterone (DHEAS), insulin-like growth factor 1 (IGF-1), growth hormone (GH) and cortisol], plasma methoxyamines (metanephrine and normetanephrine) and calcium metabolism parameters [parathyroid hormone (PTH), Ca, vitamin D3]. Osteocalcin reached similar low levels in both AN age subgroups. sCTX levels were found to be elevated in all AN subjects and higher in mature adolescents than in adult AN (11,567+/-895 vs. 8976+/-805 pmol/l, p<0.05). sALP was significantly lower only in mature adolescent AN patients, while there were no significant differences in the levels of TRAP 5b between AN patients and age-matched control groups. Osteocalcin correlated with sCTX in the control subjects (r=0.65) but not in the AN patients, suggesting the independent regulation of these markers in AN patients. Osteocalcin levels strongly correlated with freeT3, IGF-I, 17 beta estradiol and cortisol, while sCTX correlated with IGF-I, GH and cortisol in both

Parathyroid Hormone Levels and Cognition

NASA Technical Reports Server (NTRS)

Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

2009-01-01

Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

Thyroid Hormone Regulation of Metabolism

PubMed Central

Mullur, Rashmi; Liu, Yan-Yun

2014-01-01

Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5′-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets. PMID:24692351

Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action.

PubMed

Ansar Ahmed, S; Penhale, W J; Talal, N

1985-12-01

Immune reactivity is greater in females than in males. In both experimental animals and in man there is a greater preponderance of autoimmune diseases in females, compared with males. Studies in many experimental models have established that the underlying basis for this sex-related susceptibility is the marked effects of sex hormones. Sex hormones influence the onset and severity of immune-mediated pathologic conditions by modulating lymphocytes at all stages of life, prenatal, prepubertal, and postpubertal. However, despite extensive studies, the mechanisms of sex hormone action are not precisely understood. Earlier evidence suggested that the sex hormones acted via the thymus gland. In recent years it has become apparent that sex hormones can also influence the immune system by acting on several nonclassic target sites such as the immune system itself (nonthymic lymphoid organs), the central nervous system, the macrophage-macrocyte system, and the skeletal system. Immunoregulatory T cells appear to be most sensitive to sex hormone action among lymphoid cells. Several mechanisms of action of sex hormones are discussed in this review. The possibility of using sex hormone modulation of immune responses for the treatment of autoimmune disorders is a promising area for future investigation.

The T3-induced gene KLF9 regulates oligodendrocyte differentiation and myelin regeneration

PubMed Central

Dugas, Jason C.; Ibrahim, Adiljan; Barres, Ben A.

2015-01-01

Hypothyroidism is a well-described cause of hypomyelination. In addition, thyroid hormone (T3) has recently been shown to enhance remyelination in various animal models of CNS demyelination. What are the ways in which T3 promotes the development and regeneration of healthy myelin? To begin to understand the mechanisms by which T3 drives myelination, we have identified genes regulated specifically by T3 in purified oligodendrocyte precursor cells (OPCs). Among the genes identified by genomic expression analyses were four transcription factors, Kruppel-like factor 9 (KLF9), basic helix-loop-helix family member e22 (BHLHe22), Hairless (Hr), and Albumin D box-binding protein (DBP), all of which were induced in OPCs by both brief and long term exposure to T3. To begin to investigate the role of these genes in myelination, we focused on the most rapidly and robustly induced of these, KLF9, and found it is both necessary and sufficient to promote oligodendrocyte differentiation in vitro. Surprisingly, we found that loss of KLF9 in vivo negligibly affects the formation of CNS myelin during development, but does significantly delay remyelination in cuprizone-induced demyelinated lesions. These experiments indicate that KLF9 is likely a novel integral component of the T3-driven signaling cascade that promotes the regeneration of lost myelin. Future analyses of the roles of KLF9 and other identified T3-induced genes in myelination may lead to novel insights into how to enhance the regeneration of myelin in demyelinating diseases such as multiple sclerosis. PMID:22472204

Increased cell membrane permeability to Na+ and K+ induced by thyroid hormone in rat skeletal muscle.

PubMed

Asano, Y

1978-01-01

Thyroid hormone (T3) increased Na+ dependent respiration accompanied by an increase in NaK-ATPase activity. Administration of T3 increased intracellular K+ concentration and Na/K ratio in thyroidectomized rats, and the Na+ efflux rate constant incubated in oxygenized Na+, K+-Ringers in euthyroid rats. However, the magnitude of the changes in intracellular K+ concentration was modest or invisible in comparison to the changes in QO2(t) and NaK-ATPase activity. The Na+ and K+ efflux rate constants in K+-free +ouabain Ringers were increased by T3 in both thyroidectomized and euthyroid rats. Thus, thyroid hormone stimulates not only Na pump but also the permeability of cell membrane to Na+ and K+. The both effects might contribute to the thyroid thermogenesis.

Hormone Replacement Therapy and Physical Function in Healthy Older Men. Time to Talk Hormones?

PubMed Central

Giannoulis, Manthos G.; Martin, Finbarr C.; Nair, K. Sreekumaran; Umpleby, A. Margot

2012-01-01

Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established

Increased insulin sensitivity in intrauterine growth retarded newborns--do thyroid hormones play a role?

PubMed

Setia, Sajita; Sridhar, M G; Koner, B C; Bobby, Zachariah; Bhat, Vishnu; Chaturvedula, Lata

2007-02-01

Thyroid hormones are necessary for normal brain development. We studied thyroid hormone profile and insulin sensitivity in intrauterine growth retarded (IUGR) newborns to find correlation between insulin sensitivity and thyroid status in IUGR newborns. Fifty IUGR and fifty healthy control infants were studied at birth. Cord blood was collected for determination of T(3), T(4), TSH, glucose and insulin levels. IUGR newborns had significantly lower insulin, mean+/-S.D., 5.25+/-2.81 vs. 11.02+/-1.85microU/ml, but significantly higher insulin sensitivity measured as glucose to insulin ratio (G/I), 9.80+/-2.91 vs. 6.93+/-1.08 compared to healthy newborns. TSH was also significantly higher 6.0+/-2.70 vs. 2.99+/-1.05microU/ml with significantly lower T(4), 8.65+/-1.95 vs. 9.77+/-2.18microg/dl, but similar T(3) levels, 100.8+/-24.36 vs. 101.45+/-23.45ng/dl. On stepwise linear regression analysis in IUGR infants, insulin sensitivity was found to have a significant negative association with T(4) and significant positive association with TSH. Thyroid hormones may play a role in increased insulin sensitivity at birth in IUGR.

Isoflavone Malonyltransferases GmIMaT1 and GmIMaT3 Differently Modify Isoflavone Glucosides in Soybean (Glycine max) under Various Stresses

PubMed Central

Ahmad, Muhammad Z.; Li, Penghui; Wang, Junjie; Rehman, Naveed Ur; Zhao, Jian

2017-01-01

Malonylated isoflavones are the major forms of isoflavonoids in soybean plants, the genes responsible for their biosyntheses are not well understood, nor their physiological functions. Here we report a new benzylalcohol O-acetyltransferase, anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase, deacetylvindoline 4-O-acetyltransferase (BAHD) family isoflavone glucoside malonyltransferase GmIMaT1, and GmIMaT3, which is allelic to the previously characterized GmMT7 and GmIF7MaT. Biochemical studies showed that recombinant GmIMaT1 and GmIMaT3 enzymes used malonyl-CoA and several isoflavone 7-O-glucosides as substrates. The Km values of GmIMaT1 for glycitin, genistin, and daidzin were 13.11, 23.04, and 36.28 μM, respectively, while these of GmIMaT3 were 12.94, 26.67, and 30.12 μM, respectively. Transgenic hairy roots overexpressing both GmIMaTs had increased levels of malonyldaidzin and malonylgenistin, and contents of daidzin and glycitin increased only in GmIMaT1-overexpression lines. The increased daidzein and genistein contents were detected only in GmIMaT3-overexpression lines. Knockdown of GmIMaT1 and GmIMaT3 reduced malonyldaidzin and malonylgenistin contents, and affected other isoflavonoids differently. GmIMaT1 is primarily localized to the endoplasmic reticulum while GmIMaT3 is primarily in the cytosol. By examining their transcript changes corresponding to the altered isoflavone metabolic profiles under various environmental and hormonal stresses, we probed the possible functions of GmIMaTs. Two GmIMaTs displayed distinct tissue expression patterns and respond differently to various factors in modifying isoflavone 7-O-glucosides under various stresses. PMID:28559900

Analysis and functional characterization of sequence variations in ligand binding domain of thyroid hormone receptors in autism spectrum disorder (ASD) patients.

PubMed

Kalikiri, Mahesh Kumar; Mamidala, Madhu Poornima; Rao, Ananth N; Rajesh, Vidya

2017-12-01

Autism spectrum disorder (ASD) is a neuro developmental disorder, reported to be on a rise in the past two decades. Thyroid hormone-T3 plays an important role in early embryonic and central nervous system development. T3 mediates its function by binding to thyroid hormone receptors, TRα and TRβ. Alterations in T3 levels and thyroid receptor mutations have been earlier implicated in neuropsychiatric disorders and have been linked to environmental toxins. Limited reports from earlier studies have shown the effectiveness of T3 treatment with promising results in children with ASD and that the thyroid hormone levels in these children was also normal. This necessitates the need to explore the genetic variations in the components of the thyroid hormone pathway in ASD children. To achieve this objective, we performed genetic analysis of ligand binding domain of THRA and THRB receptor genes in 30 ASD subjects and in age matched controls from India. Our study for the first time reports novel single nucleotide polymorphisms in the THRA and THRB receptor genes of ASD individuals. Autism Res 2017, 10: 1919-1928. ©2017 International Society for Autism Research, Wiley Periodicals, Inc. Thyroid hormone (T3) and thyroid receptors (TRα and TRβ) are the major components of the thyroid hormone pathway. The link between thyroid pathway and neuronal development is proven in clinical medicine. Since the thyroid hormone levels in Autistic children are normal, variations in their receptors needs to be explored. To achieve this objective, changes in THRA and THRB receptor genes was studied in 30 ASD and normal children from India. The impact of some of these mutations on receptor function was also studied. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

The evolutionary and integrative roles of transthyretin in thyroid hormone homeostasis.

PubMed

Schreiber, G

2002-10-01

In larger mammals, thyroid hormone-binding plasma proteins are albumin, transthyretin (TTR) and thyroxine (T4)-binding globulin. They differ characteristically in affinities and release rates for T4 and triiodothyronine (T3). Together, they form a 'buffering' system counteracting thyroid hormone permeation from aqueous to lipid phases. Evolution led to important differences in the expression pattern of these three proteins in tissues. In adult liver, TTR is only made in eutherians and herbivorous marsupials. During development, it is also made in tadpole and fish liver. More intense TTR synthesis than in liver is found in the choroid plexus of reptilians, birds and mammals, but none in the choroid plexus of amphibians and fish, i.e. species without a neocortex. All brain-made TTR is secreted into the cerebrospinal fluid, where it becomes the major thyroid hormone-binding protein. During ontogeny, the maximum TTR synthesis in the choroid plexus precedes that of the growth rate of the brain and occurs during the period of maximum neuroblast replication. TTR is only one component in a network of factors determining thyroid hormone distribution. This explains why, under laboratory conditions, TTR-knockout mice show no major abnormalities. The ratio of TTR affinity for T4 over affinity for T3 is higher in eutherians than in reptiles and birds. This favors T4 transport from blood to brain providing more substrate for conversion of the biologically less active T4 into the biologically more active T3 by the tissue-specific brain deiodinases. The change in affinity of TTR during evolution involves a shortening and an increase in the hydrophilicity of the N-terminal regions of the TTR subunits. The molecular mechanism for this change is a stepwise shift of the splice site at the intron 1/exon 2 border of the TTR gene. The shift probably results from a sequence of single base mutations. Thus, TTR evolution provides an example for a molecular mechanism of positive Darwinian

Persistence of a circadian rhythmicity for thyroid hormones in plasma and thyroid of hibernating male Rana ridibunda.

PubMed

Kühn, E R; Delmotte, N M; Darras, V M

1983-06-01

The presence and circadian rhythmicity of thyroid hormones was studied in plasma and the thyroid gland of male Rana ridibunda before and during hibernation. Hibernating January frogs do have a lower T3 and T4 content of their thyroid gland whereas plasma levels of T3 are maintained and of T4 increased compared to fed September or October frogs. It seems likely that the increased photoperiod in January will be responsible for this increased T4 secretion, since controlled laboratory experiments performed in December did not reveal any influence of low temperature on circulating T3 or T4 levels. Also feeding does not influence circulating levels and thyroid content of thyroid hormones in frogs kept at room temperature during the month of January. A circadian rhythmicity of T3 and T4 in the thyroid gland is present in fed October frogs and in non fed December frogs acclimated at 5 degrees C for 12 days with an acrophase for T3 at approximately 1500 h and for T4 at around 1900 h, whereas in plasma only T3 does have circadian variations (acrophase about midnight) but not T4. When December frogs are acclimated to room temperature for 12 days, frogs are active again, but do not eat and have a lower body weight than frogs hibernating at 5 degrees C. Their T3 content of the thyroid gland has disappeared, but T4 thyroid content and plasma levels of T3 and T4 are maintained. As in hibernating frogs, no circadian variations in T4 plasma concentrations are present whereas the circadian thyroid T4 rhythm disappears. At the same time a dampening in rhythmicity for plasma T3 as judged by the significantly lower amplitude occurs. It is concluded that the persistence of circulating levels of thyroid hormones and of a circadian cyclicity for T3 in plasma in non feeding hibernating frogs may reflect the special metabolic state e.g. availability of food reserves in these animals.

Immunologic Intervention in HIV Infection: Anti-Polymerase Responses and Hormonal Regulation

DTIC Science & Technology

1993-09-01

chronic human immunodeficiency virus infection is blocked in vitro by a methylphosphonate oligodeoxynucleoside targeted to a U3/enhancer element. J...Grimison B, Gonenne A. 1992. Effect of recombinant human growth hormone on acute and chronic human immunodeficiency virus infection in vitro. Blood 79...Kong X-B, Chou T-C. Interactions of recombinant human growth hormone with dideoxynucleoside inhibitors of human immunodeficiency virus. Blood, in

Estriol administration modulates luteinizing hormone secretion in women with functional hypothalamic amenorrhea.

PubMed

Genazzani, Alessandro D; Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Santagni, Susanna; Rattighieri, Erica; Ricchieri, Federica; Chierchia, Elisa; Simoncini, Tommaso

2012-02-01

To evaluate the influence of estriol administration on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study. Patients with FHA in a clinical research environment. Twelve hypogonadotropic patients affected by FHA. Pulsatility study of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and a gonadotropin-releasing hormone (GnRH) test (10 μg in bolus) at baseline condition and after 8 weeks of therapy with 2 mg/day of estriol. Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione (A), 17α-hydroxyprogesterone (17-OHP), cortisol, androstenedione (A), testosterone (T), thyroid-stimulating hormone (TSH), free triiodothyronine (fT(3)), free thyroxine (fT(4)), and insulin, and pulse detection. After treatment, the FHA patients showed a statistically significant increase of LH plasma levels (from 0.7 ± 0.1 mIU/mL to 3.5 ± 0.3 mIU/mL) and a statistically significant increase of LH pulse amplitude with no changes in LH pulse frequency. In addition, the LH response to the GnRH bolus was a statistically significant increase. Estriol administration induced the increase of LH plasma levels in FHA and improved GnRH-induced LH secretion. These findings suggest that estriol administration modulates the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of LH synthesis and secretion in hypogonadotropic patients with FHA. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Role of thyroidal and testicular hormones in regulation of tissue respiration in male air-breathing fish, Clarias batrachus (Linn.).

PubMed

Lynshiang, D S; Gupta, B B

2000-07-01

In vivo and in vitro effects of thyroidal hormones (MIT, DIT, T3, T4), propyl thiouracil (PTU), testosterone and cyproterone acetate were studied on the rate of tissue (liver, muscle, kidney and brain) respiration of adult male C. batrachus during winter and summer/rainy seasons. Monoiodotyrosine (MIT) and diiodothyrosine (DIT) increased the respiratory rate in a dose-dependent and temperature-independent manner. Triiodothyronine (T3) and thyroxine (T4) stimulated tissue respiration during summer/rainy months but not during winter. PTU decreased tissue respiration during summer/rainy season and also at simulated low temperature. Testosterone invariably stimulated the rate of respiration of the tissues, while in vivo treatment with cyproterone acetate significantly decreased the metabolic rate of all the tissues. The findings suggest that in C. batrachus MIT and DIT may be more important than T3 and T4 at low temperature, endogenous thyroid hormones are involved indirectly in energy metabolism even during winter/at low temperature and testicular hormones are actively involved in the respiration.

Comparison of cortisol and thyroid hormones between tuberculosis-suspect and healthy elephants of Nepal.

PubMed

Paudel, Sarad; Brown, Janine L; Thapaliya, Sharada; Dhakal, Ishwari P; Mikota, Susan K; Gairhe, Kamal P; Shimozuru, Michito; Tsubota, Toshio

2016-12-01

We compared cortisol and thyroid hormone (T3 and T4) concentrations between tuberculosis (TB)-suspected (n=10) and healthy (n=10) elephants of Nepal. Whole blood was collected from captive elephants throughout Nepal, and TB testing was performed using the ElephantTB STAT-PAK ® and DPP VetTB ® serological assays that detect antibodies against Mycobacterium tuberculosis and M. bovis in elephant serum. Cortisol, T3 and T4 were quantified by competitive enzyme immunoassays, and the results showed no significant differences in hormone concentrations between TB-suspect and healthy elephants. These preliminary data suggest neither adrenal nor thyroid function is altered by TB disease status. However, more elephants, including those positively diagnosed for TB by trunk wash cultures, need to be evaluated over time to confirm results.

Alteration of thyroid hormone concentrations in juvenile Chinook salmon (Oncorhynchus tshawytscha) exposed to polybrominated diphenyl ethers, BDE-47 and BDE-99.

PubMed

Arkoosh, Mary R; Van Gaest, Ahna L; Strickland, Stacy A; Hutchinson, Greg P; Krupkin, Alex B; Dietrich, Joseph P

2017-03-01

Polybrominated diphenyl ethers (PBDEs) have been used as flame-retardants in consumer products and are currently detected in salmon globally. The two most predominant PBDE congeners found in salmon are BDE-47 (2,2',4,4'-tetrabromodiphenyl ether) and BDE-99 (2,2',4,4',5-pentabromodiphenyl ether). In the present study, groups of juvenile Pacific Chinook salmon were fed five environmentally relevant concentrations of either BDE-47 (0.3-552 ng total PBDEs/g food), BDE-99 (0.3-580 ng total PBDEs/g food), or nearly equal mixtures of both congeners (0.7-690 ng total PBDEs/g food) for 39-40 days. The concentrations of circulating total thyroid hormones, thyroxine (T 4 ) and 3,5,3'-triiodothyronine (T 3 ), were measured using a hormone-specific time-resolved fluoroimmunoassay to determine if PBDE exposure disrupts the hypothalamic-pituitary-thyroid endocrine axis. The concentrations of both circulating T 4 and T 3 were altered in juvenile salmon by dietary uptake of BDE-99. Exposure to BDE-47 did not alter either T 3 or T 4 circulating hormone concentrations. However, exposure to a mixture of BDE-47 and BDE-99 reduced T 3 in fish with lower concentrations of total whole body PBDEs than with either congener alone at equivalent PBDE whole body concentrations. Accordingly, the disruption of PBDEs on circulating thyroid hormone concentrations has the potential to impact a number of critical functions in juvenile salmon including growth, parr-smolt transformation, and immunological processes. Published by Elsevier Ltd.

Successful every-other-day liothyronine therapy for severe resistance to thyroid hormone beta with a novel THRB mutation; case report.

PubMed

Maruo, Yoshihiro; Mori, Asami; Morioka, Yoriko; Sawai, Chihiro; Mimura, Yu; Matui, Katsuyuki; Takeuchi, Yoshihiro

2016-01-12

Resistance to thyroid hormone beta (RTHβ) is a rare and usually dominantly inherited syndrome caused by mutations of the thyroid hormone receptor β gene (THRB). In severe cases, it is rarely challenging to control manifestations using daily therapeutic replacement of thyroid hormone. The present case study concerns an 8-year-old Japanese girl with a severe phenotype of RTH (TSH, fT3, and fT4 were 34.0 mU/L, >25.0 pg/mL and, >8.0 ng/dL, respectively), caused by a novel heterozygous frameshift mutation in exon 10 of the thyroid hormone receptor beta gene (THRB), c.1347-1357 del actcttccccc : p.E449DfsX11. RTH was detected at the neonatal screening program. At 4 years of age, the patient continued to suffer from mental retardation, hyperactivity, insomnia, and reduced resting energy expenditure (REE), despite daily thyroxine (L-T4) therapy. Every-other-day high-dose liothyronine (L-T3) therapy improved her symptoms and increased her REE, without thyrotoxicosis. In a case of severe RTH, every-other-day L-T3 administration enhanced REE and psychomotor development, without promoting symptoms of thyrotoxicosis. Every-other-day L-T3 administration may be an effective strategy for the treatment of severe RTH.

Sex steroid hormones and sex hormone binding globulin levels, CYP17 MSP AI (-34T:C) and CYP19 codon 39 (Trp:Arg) variants in children with developmental stuttering.

PubMed

Mohammadi, Hiwa; Joghataei, Mohammad Taghi; Rahimi, Zohreh; Faghihi, Faezeh; Khazaie, Habibolah; Farhangdoost, Hashem; Mehrpour, Masoud

2017-12-01

Developmental stuttering is known to be a sexually dimorphic and male-biased speech motor control disorder. In the present case-control study, we investigated the relationship between developmental stuttering and steroid hormones. Serum levels of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), oestradiol, progesterone, cortisol, and sex hormone binding globulin (SHBG), as well as the 2nd/4th digit ratio (2D:4D), an indicator of prenatal testosterone level, were compared between children who stutter (CWS) and children who do not stutter (CWNS). Moreover, two SNPs (CYP17 -34 T:C (MSP AI) and CYP19 T:C (Trp:Arg)) of cytochrome P450, which is involved in steroid metabolism pathways, were analysed between the groups. Our results showed significantly higher levels of testosterone, DHT, and oestradiol in CWS in comparison with CWNS. The severity of stuttering was positively correlated with the serum levels of testosterone, DHEA, and cortisol, whereas no association was seen between the stuttering and digit ratio, progesterone, or SHBG. The CYP17CC genotype was significantly associated with the disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of thyroid hormones in stress response of fish.

PubMed

Peter, M C Subhash

2011-06-01

Thyroxine (T(4)) and triiodothyronine (T(3)), the principal thyroid hormones (THs) secreted from the hypothalamic-pituitary-thyroid (HPT) axis, produce a plethora of physiologic actions in fish. The diverse actions of THs in fishes are primarily due to the sensitivity of thyroid axis to many physical, chemical and biological factors of both intrinsic and extrinsic origins. The regulation of THs homeostasis becomes more complex due to extrathyroidal deiodination pathways by which the delivery of biologically active T(3) to target cells has been controlled. As primary stress hormones and the end products of hypothalamic-pituitary-interrenal (HPI) and brain-sympathetic-chromaffin (BSC) axes, cortisol and adrenaline exert its actions on its target tissues where it promote and integrate osmotic and metabolic competence. Despite possessing specific osmoregulatory and metabolic actions at cellular and whole-body levels, THs may fine-tune these processes in accordance with the actions of hormones like cortisol and adrenaline. Evidences are presented that THs can modify the pattern and magnitude of stress response in fishes as it modifies either its own actions or the actions of stress hormones. In addition, multiple lines of evidence indicate that hypothalamic and pituitary hormones of thyroid and interrenal axes can interact with each other which in turn may regulate THs/cortisol-mediated actions. Even though it is hard to define these interactions, the magnitude of stress response in fish has been shown to be modified by the changes in the status of THs, pointing to its functional relationship with endocrine stress axes particularly with the interrenal axis. The fine-tuned mechanism that operates in fish during stressor-challenge drives the THs to play both fundamental and modulator roles in stress response by controlling osmoregulation and metabolic regulation. A major role of THs in stress response is thus evident in fish. Copyright © 2011 Elsevier Inc. All rights

Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action.

PubMed Central

Ansar Ahmed, S.; Penhale, W. J.; Talal, N.

1985-01-01

Immune reactivity is greater in females than in males. In both experimental animals and in man there is a greater preponderance of autoimmune diseases in females, compared with males. Studies in many experimental models have established that the underlying basis for this sex-related susceptibility is the marked effects of sex hormones. Sex hormones influence the onset and severity of immune-mediated pathologic conditions by modulating lymphocytes at all stages of life, prenatal, prepubertal, and postpubertal. However, despite extensive studies, the mechanisms of sex hormone action are not precisely understood. Earlier evidence suggested that the sex hormones acted via the thymus gland. In recent years it has become apparent that sex hormones can also influence the immune system by acting on several nonclassic target sites such as the immune system itself (nonthymic lymphoid organs), the central nervous system, the macrophage-macrocyte system, and the skeletal system. Immunoregulatory T cells appear to be most sensitive to sex hormone action among lymphoid cells. Several mechanisms of action of sex hormones are discussed in this review. The possibility of using sex hormone modulation of immune responses for the treatment of autoimmune disorders is a promising area for future investigation. Images Figure 1 PMID:3907369

Assembly of insect hormone enthusiasts at Nasu Highland, Japan: Report of the 3rd International Insect Hormone (21st Ecdysone) Workshop.

PubMed

Niwa, Ryusuke; Nishimura, Takashi

2018-01-01

The 3rd International Insect Hormone (21st Ecdysone) Workshop (IIHW2017) was held in July 2017 at Nasu Highland, Japan. In the 40 years of the workshop's history, this was the first to be held in an Asian country. A total of 109 insect hormone researchers from 18 countries (62 overseas and 47 domestic participants) attended IIHW2017. During the workshop, all participants stayed on-site at the venue's hotel; this was ideal for fostering communication between participants, in particular, interactions between principal investigators and young scientists. The workshop featured one keynote, 64 oral, and 35 poster presentations spanning molecular biology, cell biology, developmental biology, neurobiology, chemical biology, physiology, and ecology of insect hormones, including ecdysteroids, juvenile hormones, and a variety of neuropeptides. The workshop provided an ideal platform for discussing insect hormone biology using not only the typical genetic model insect, the fruit fly Drosophila, but also a diversity of interesting insects, such as the silkworm, the red flour beetle, the cricket, the dragonfly, the social ant, the bloodsucking tick, and so on. The participants succeeded in sharing the latest knowledge in a wide range of insect hormone research fields and in joining active and constructive scientific discussions. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice

PubMed Central

Peroni, Cibele N.; Hayashida, Cesar Y.; Nascimento, Nancy; Longuini, Viviane C.; Toledo, Rodrigo A.; Bartolini, Paolo; Bowers, Cyril Y.; Toledo, Sergio P.A.

2012-01-01

OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormone-releasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/lit mice, which represent a model of GH deficiency arising from mutated growth hormone-releasing hormone-receptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a. PMID:22473409

The effect of thyroid hormone and a long-acting somatostatin analogue on TtT-97 murine thyrotropic tumors.

PubMed

Woodmansee, W W; Gordon, D F; Dowding, J M; Stolz, B; Lloyd, R V; James, R A; Wood, W M; Ridgway, E C

2000-07-01

Thyroid hormone inhibits thyrotropin (TSH) production and thyrotrope growth. Somatostatin has been implicated as a synergistic factor in the inhibition of thyrotrope function. We have previously shown that pharmacological doses of thyroid hormone (levothyroxine [LT4]) inhibit growth of murine TtT-97 thyrotropic tumors in association with upregulation of somatostatin receptor type 5 (sst5) mRNA and somatostatin receptor binding. In the current study, we examined the effect of physiological thyroid hormone replacement alone or in combination with the long-acting somatostatin analogue, Sandostatin LAR, on thyrotropic tumor growth, thyrotropin growth factor-beta (TSH-beta), and sst5 mRNA expression, as well as somatostatin receptor binding sites. Physiological LT4 replacement therapy resulted in tumor shrinkage in association with increased sst5 mRNA levels, reduced TSH-beta mRNA levels and enhanced somatostatin receptor binding. Sandostatin LAR alone had no effect on any parameter measured. However, Sandostatin LAR combined with LT4 synergistically inhibited TSH-beta mRNA production and reduced final tumor weights to a greater degree. In this paradigm, Sandostatin LAR required a euthyroid status to alter thyrotrope parameters. These data suggest an important interaction between the somatostatinergic system and thyroid hormone in the regulation of thyrotrope cell structure and function.

The mechanism of the calorigenic action of thyroid hormone. Stimulation of Na plus + K plus-activated adenosinetriphosphatase activity.

PubMed

Ismail-Beigi, F; Edelman, I S

1971-06-01

In an earlier study, we proposed that thyroid hormone stimulation of energy utilization by the Na(+) pump mediates the calorigenic response. In this study, the effects of triiodothyronine (T(3)) on total oxygen consumption (Q(OO2)), the ouabain-sensitive oxygen consumption [Q(OO2)(t)], and NaK-ATPase in liver, kidney, and cerebrum were measured. In liver, approximately 90% of the increase in Q(OO2) produced by T(3) in either thyroidectomized or euthyroid rats was attributable to the increase in Q(OO2)(t). In kidney, the increase in Q(OO2)(t) accounted for 29% of the increase in Q(OO2) in thyroidectomized and 46% of the increase in Q(OO2) in euthyroid rats. There was no demonstrable effect of T(3) in euthyroid rats on Q(OO2) or Q(OO2)(t) of cerebral slices. The effects of T(3) on NaK-ATPase activity in homogenates were as follows: In liver +81% from euthyroid rats and +54% from hypothyroid rats. In kidney, +21% from euthyroid rats and +69% from hypothyroid rats. T(3) in euthyroid rats produced no significant changes in NaK-ATPase or Mg-ATPase activity of cerebral homogenates. Liver plasma membrane fractions showed a 69% increase in NaK-ATPase and no significant changes in either Mg-ATPase or 5'-nucleotidase activities after T(3) injection. These results indicate that thyroid hormones stimulate NaK-ATPase activity differentially. This effect may account, at least in part, for the calorigenic effects of these hormones.

The Thyroid Hormone Receptors Inhibit Hepatic Interleukin-6 Signaling During Endotoxemia.

PubMed

Contreras-Jurado, Constanza; Alonso-Merino, Elvira; Saiz-Ladera, Cristina; Valiño, Arturo José; Regadera, Javier; Alemany, Susana; Aranda, Ana

2016-08-03

Decreased thyroidal hormone production is found during lipopolysaccharide (LPS)-induced endotoxic shock in animals as well as in critically ill patients. Here we studied the role of the thyroid hormone receptors (TRs) in activation of STAT3, NF-κB and ERK, which play a key role in the response to inflammatory cytokines during sepsis. TR knockout mice showed down-regulation of hepatic inflammatory mediators, including interleukin 6 (IL-6) in response to LPS. Paradoxically, STAT3 and ERK activity were higher, suggesting that TRs could act as endogenous repressors of these pathways. Furthermore, hyperthyroidism increased cytokine production and mortality in response to LPS, despite decreasing hepatic STAT3 and ERK activity. This suggested that TRs could directly repress the response of the cells to inflammatory mediators. Indeed, we found that the thyroid hormone T3 suppresses IL-6 signalling in macrophages and hepatocarcinoma cells, inhibiting STAT3 activation. Consequently, the hormone strongly antagonizes IL-6-stimulated gene transcription, reducing STAT3 recruitment and histone acetylation at IL-6 target promoters. In conclusion, TRs are potent regulators of inflammatory responses and immune homeostasis during sepsis. Reduced responses to IL-6 should serve as a negative feedback mechanism for preventing deleterious effects of excessive hormone signaling during infections.

The Thyroid Hormone Receptors Inhibit Hepatic Interleukin-6 Signaling During Endotoxemia

PubMed Central

Contreras-Jurado, Constanza; Alonso-Merino, Elvira; Saiz-Ladera, Cristina; Valiño, Arturo José; Regadera, Javier; Alemany, Susana; Aranda, Ana

2016-01-01

Decreased thyroidal hormone production is found during lipopolysaccharide (LPS)-induced endotoxic shock in animals as well as in critically ill patients. Here we studied the role of the thyroid hormone receptors (TRs) in activation of STAT3, NF-κB and ERK, which play a key role in the response to inflammatory cytokines during sepsis. TR knockout mice showed down-regulation of hepatic inflammatory mediators, including interleukin 6 (IL-6) in response to LPS. Paradoxically, STAT3 and ERK activity were higher, suggesting that TRs could act as endogenous repressors of these pathways. Furthermore, hyperthyroidism increased cytokine production and mortality in response to LPS, despite decreasing hepatic STAT3 and ERK activity. This suggested that TRs could directly repress the response of the cells to inflammatory mediators. Indeed, we found that the thyroid hormone T3 suppresses IL-6 signalling in macrophages and hepatocarcinoma cells, inhibiting STAT3 activation. Consequently, the hormone strongly antagonizes IL-6-stimulated gene transcription, reducing STAT3 recruitment and histone acetylation at IL-6 target promoters. In conclusion, TRs are potent regulators of inflammatory responses and immune homeostasis during sepsis. Reduced responses to IL-6 should serve as a negative feedback mechanism for preventing deleterious effects of excessive hormone signaling during infections. PMID:27484112

Hormone levels of world class cyclists during the Tour of Spain stage race

PubMed Central

Lucia, A; Diaz, B; Hoyos, J; Fernandez, C; Villa, G; Bandres, F; Chicharro, J

2001-01-01

Objectives—To evaluate the hormonal response to strenuous endurance exercise performed by elite athletes. Methods—Nine professional cyclists (mean (SD) age 28 (1) years; mean (SD) VO2MAX 75.3 (2.3) ml/kg/min) who participated in a three week tour race (Vuelta a España 1999) were selected as subjects. Morning urinary levels of 6-sulphatoxymelatonin (aMT6s) and morning serum levels of testosterone, follicle stimulating (FSH), luteinising hormone (LH), and cortisol were measured in each subject at t0 (before the competition), t1 (end of first week), t2 (end of second week), and t3 (end of third week). Urine samples of aMT6s were also evaluated in the evening at t0, t1, t2, and t3. Results—Mean urinary aMT6s levels had increased significantly (p<0.01) during the day after each stage (1091 (33) v 683 (68) ng/ml at t1; 955 (19) v 473 (53) ng/ml at t2; 647 (61) v 337 (47) ng/ml at t3). Both morning and evening aMT6s levels decreased significantly during the study. A similar pattern was observed for morning serum levels of cortisol and testosterone. Conclusions—The results suggest that the basal activity of the pineal gland, adrenal glands, and testis may be decreased after consecutive days of intense, long term exercise. Key Words: melatonin; gonadotrophins; testosterone; cortisol; endurance exercise PMID:11726480

Deiodinases, Organic Anion Transporter Polypeptide Polymorphisms, and Thyroid Hormones in Patients with Myocardial Infarction.

PubMed

Brozaitiene, Julija; Skiriute, Daina; Burkauskas, Julius; Podlipskyte, Aurelija; Jankauskiene, Edita; Serretti, Alessandro; Mickuviene, Narseta

2018-04-01

To investigate the association among deiodinases (DIO), organic anion-transporting polypeptide 1C1 (OATP1C1) gene polymorphisms, and thyroid hormones (THs) in patients with acute myocardial infarction (AMI). In summary, 290 patients with AMI were evaluated for sociodemographic and clinical characteristics, coronary artery disease (CAD) risk factors, and comorbidities, as well as circulating thyroid-stimulating hormone and TH (triiodothyronine [T3], thyroxine [T4], free T3, free T4, and reverse T3) levels. Ten single nucleotide polymorphisms for thyroid axis related genes: DIO1 (rs11206244-C/T, rs12095080-A/G, rs2235544-A/C), DIO2 (rs225014-T/C, rs225015-G/A), DIO3 (rs945006-T/G), and OATP1C1 (rs10444412-T/C, rs10770704-C/T, rs1515777-A/G, rs974453-G/A) were genotyped. Marginal associations were observed between the DIO1, DIO2, and OATP1C1 gene polymorphisms and almost all analyzed THs (p's < 0.05). After controlling for potential confounders, the OATP1C1 rs1515777-A/G minor allele homozygous genotype (G/G) was associated with a decrease in circulating free T3 and free T3/free T4. In the AMI cohort, associations between: DIO1 rs12095080 and hypertension; DIO2 rs225015 and diabetes mellitus; and the OATP1C1 rs974453 genotype, and AMI type were established. DIO1 and DIO2 gene polymorphisms are mainly associated with T3, free T4, free T3/free T4, and [natural-log transformed (ln)] reverse T3 levels, while the OATP1C1 minor allele homozygous genotype is associated with free T3 and free T3/free T4 in CAD patients after AMI.

Sex-steroid and thyroid hormone concentrations in juvenile alligators (Alligator mississippiensis) from contaminated and reference lakes in Florida, USA

USGS Publications Warehouse

Grain, D.A.; Guillette, L.J.; Pickford, D.B.; Percival, H.F.; Woodward, A.R.

1998-01-01

Sex-steroid and thyroid hormones are critical regulators of growth and reproduction in all vertebrates, and several recent studies suggest that environmental chemicals can alter circulating concentrations of these hormones. This study examines plasma concentrations of estradiol-171?? (E2), testosterone (T), triiodothyronine (T3), and thyroxine (T4) in juvenile alligators (60-140 cm total length) from two contaminated lakes and one reference lake in Florida. First, the data were analyzed by comparing hormone concentrations among males and females from the different lakes. Whereas there were no differences in plasma E2 concentrations among animals of the three lakes, male alligators from the contaminated lakes (Lake Apopka and Lake Okeechobee) had significantly lower plasma T concentrations compared 10 males from the reference take (Lake Woodruff). Concentrations of thyroid hormones also differed in animals of the three lakes, with T4 concentrations being elevated in Lake Okeechobee males compared to Lake Woodruff males. Second, the relationship between body size and hormone concentration was examined using regression analysis. Most notably for steroid hormones, no clear relationship was detected between E2 and total length in Apopka females (r2 0.09, p = 0.54) or between T and total length in Apopka males (r2 = 0.007, p = 0.75). Females from Apopka (r2 = 0.318, p = 0.09) and Okeechobee (r2 = 0.222, p = 0.09) exhibited weak correlations between T3 and total length. Males from Apopka (r2 = 0.015, p = 0.66) and Okeechobee (r2 = 0.128, p = 0.19) showed no correlation between T4 and total length. These results indicate: some of the previously reported abnormalities in steroid hormones of hatchling alligators persist, at least, through the juvenile years; steroid and thyroid hormones are related to body size in juvenile alligators from the reference lake, whereas alligators living in lakes Apopka and Okeechobee experience alterations in circulating thyroid and steroid

Phloretin and phlorizin promote lipolysis and inhibit inflammation in mouse 3T3-L1 cells and in macrophage-adipocyte co-cultures.

PubMed

Huang, Wen-Chung; Chang, Wei-Tien; Wu, Shu-Ju; Xu, Pei-Yin; Ting, Nai-Chun; Liou, Chian-Jiun

2013-10-01

Previous studies found that phloretin (PT) and phlorizin (PZ) could inhibit glucose transport, with PT being a better inhibitor of lipid peroxidation. This study aimed to evaluate the antiobesity effects of PT and PZ in 3T3-L1 cells and if they can modulate the relationship between adipocytes and macrophages. Differentiated 3T3-L1 cells were treated with PT or PZ. Subsequently, transcription factors of adipogenesis and lipolysis proteins were measured. In addition, RAW 264.7 macrophages treated with PT or PZ were cultured in differentiated media from 3T3-L1 cells to analyze inflammatory mediators and signaling pathways. PT significantly enhanced glycerol release and inhibited the adipogenesis-related transcription factors. PT also promoted phosphorylation of AMP-activated protein kinase and increased activity of adipose triglyceride lipase and hormone-sensitive lipase. PT suppressed the nuclear transcription factor kappa-B and mitogen-activated protein kinase pathways when RAW 264.7 cells were cultured in differentiated media from 3T3-L1 cells. PZ improved lipolysis and inhibited the macrophage inflammatory response less effectively than PT. This study suggests that PT is more effective than PZ at increasing lipolysis in adipocytes. In addition, PT also suppresses inflammatory response in macrophage that is stimulated by differentiated media from 3T3-L1 cells. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of experimentally induced mild hyperthyroidism on growth hormone and insulin secretion and sex steroid levels in healthy young men.

PubMed

Lovejoy, J C; Smith, S R; Bray, G A; Veldhuis, J D; Rood, J C; Tulley, R

1997-12-01

Although triiodothyronine (T3) exerts major regulatory actions in both animals and humans, most clinical studies of T3 administration have been relatively short-term. The present study examined the effects of more than 2 months (63 days) of low-dose T3 treatment on overnight pulsatile growth hormone (GH) secretion, short-term insulin secretion, and of sex steroid levels in seven healthy, lean men studied at an inpatient metabolic unit. At baseline, there were strong correlations between sex hormone-binding globulin (SHBG) and several measures of GH production, including total GH production (r = .99), GH interburst interval (r = -.75), and GH mass (r = .82). SHBG was also inversely correlated with basal insulin secretion (r = -.74). There was a 42% increase in serum levels of total testosterone (18.5 +/- 1.3 to 26.3 +/- 1.8 nmol/L, P = .005) and a 150% increase in SHBG (18.0 +/- 2.2 to 44.9 +/- 7.0 nmol/L, P = .008) following T3 treatment. Estradiol and free testosterone levels were unchanged by treatment, although free testosterone decreased from 142.8 +/- 18.4 to 137.3 +/- 19.5 pmol/L. T3 treatment significantly reduced the GH interburst interval (P < .05) and produced slight increases in the measures of GH secretion. There were no statistically significant effects of T3 treatment on insulin secretion, although insulin peak amplitude, mass secreted per burst, and total production all decreased. We conclude that experimentally induced T3 excess in healthy men produces significant and sustained changes in sex hormone levels and GH secretion. Furthermore, there are strong associations between SHBG and both GH and insulin secretion independent of thyroid hormone excess that require additional study.

Hormones and immunity in cancer: are thyroid hormones endocrine players in the microglia/glioma cross-talk?

PubMed Central

Perrotta, Cristiana; De Palma, Clara; Clementi, Emilio; Cervia, Davide

2015-01-01

Accumulating evidence indicates that the endocrine and immune systems engage in complex cross-talks in which a prominent role is played by thyroid hormones (THs). The increase of resident vs. monocyte recruited macrophages was shown to be an important effector of the TH 3,3′,5′-Triiodo-L-thyronine (T3)-induced protection against inflammation and a key role of T3 in inhibiting the differentiation of peripheral monocytes into macrophages was observed. Herein, we report on the role of T3 as a modulator of microglia, the specialized macrophages of the central nervous system (CNS). Mounting evidence supports a role of microglia and macrophages in the growth and invasion of malignant glioma. In this respect, we unveil the putative involvement of T3 in the microglia/glioma cell communication. Since THs are known to cross the blood-brain barrier, we suggest that T3 not only exerts a direct modulation of brain cancer cell itself but also indirectly promotes glioma growth through a modulation of microglia. Our observations expand available information on the role of TH system in glioma and its microenvironment and highlight the endocrine modulation of microglia as an important target for future therapeutic development of glioma treatments. PMID:26157361

Regulation of microglial development: a novel role for thyroid hormone.

PubMed

Lima, F R; Gervais, A; Colin, C; Izembart, M; Neto, V M; Mallat, M

2001-03-15

The postnatal development of rat microglia is marked by an important increase in the number of microglial cells and the growth of their ramified processes. We studied the role of thyroid hormone in microglial development. The distribution and morphology of microglial cells stained with isolectin B4 or monoclonal antibody ED1 were analyzed in cortical and subcortical forebrain regions of developing rats rendered hypothyroid by prenatal and postnatal treatment with methyl-thiouracil. Microglial processes were markedly less abundant in hypothyroid pups than in age-matched normal animals, from postnatal day 4 up to the end of the third postnatal week of life. A delay in process extension and a decrease in the density of microglial cell bodies, as shown by cell counts in the developing cingulate cortex of normal and hypothyroid animals, were responsible for these differences. Conversely, neonatal rat hyperthyroidism, induced by daily injections of 3,5,3'-triiodothyronine (T3), accelerated the extension of microglial processes and increased the density of cortical microglial cell bodies above physiological levels during the first postnatal week of life. Reverse transcription-PCR and immunological analyses indicated that cultured cortical ameboid microglial cells expressed the alpha1 and beta1 isoforms of nuclear thyroid hormone receptors. Consistent with the trophic and morphogenetic effects of thyroid hormone observed in situ, T3 favored the survival of cultured purified microglial cells and the growth of their processes. These results demonstrate that thyroid hormone promotes the growth and morphological differentiation of microglia during development.

Antitumor Responses Stimulated by Dendritic Cells Are Improved by Triiodothyronine Binding to the Thyroid Hormone Receptor β.

PubMed

Alamino, Vanina A; Mascanfroni, Iván D; Montesinos, María M; Gigena, Nicolás; Donadio, Ana C; Blidner, Ada G; Milotich, Sonia I; Cheng, Sheue-Yann; Masini-Repiso, Ana M; Rabinovich, Gabriel A; Pellizas, Claudia G

2015-04-01

Bidirectional cross-talk between the neuroendocrine and immune systems orchestrates immune responses in both physiologic and pathologic settings. In this study, we provide in vivo evidence of a critical role for the thyroid hormone triiodothyronine (T3) in controlling the maturation and antitumor functions of dendritic cells (DC). We used a thyroid hormone receptor (TR) β mutant mouse (TRβPV) to establish the relevance of the T3-TRβ system in vivo. In this model, TRβ signaling endowed DCs with the ability to stimulate antigen-specific cytotoxic T-cell responses during tumor development. T3 binding to TRβ increased DC viability and augmented DC migration to lymph nodes. Moreover, T3 stimulated the ability of DCs to cross-present antigens and to stimulate cytotoxic T-cell responses. In a B16-OVA mouse model of melanoma, vaccination with T3-stimulated DCs inhibited tumor growth and prolonged host survival, in part by promoting the generation of IFNγ-producing CD8(+) T cells. Overall, our results establish an adjuvant effect of T3-TRβ signaling in DCs, suggesting an immediately translatable method to empower DC vaccination approaches for cancer immunotherapy. ©2015 American Association for Cancer Research.

Prevalence of serum thyroid hormone autoantibodies in dogs with clinical signs of hypothyroidism.

PubMed

Nachreiner, Raymond F; Refsal, Kent R; Graham, Peter A; Bowman, Mark M

2002-02-15

To determine prevalence of thyroid hormone autoantibodies (THAA) in serum of dogs with clinical signs of hypothyroidism. Cohort study. 287,948 serum samples from dogs with clinical signs consistent with hypothyroidism. Serum THAA were detected by use of a radiometric assay. Correlation and chi2 analyses were used to determine whether prevalence varied with breed, age, sex, or body weight. Only breeds for which > or = 50 samples had been submitted were used for analysis of breed prevalence. Thyroid hormone autoantibodies were detected in 18,135 (6.3%) samples. The 10 breeds with the highest prevalence of THAA were the Pointer, English Setter, English Pointer, Skye Terrier, German Wirehaired Pointer, Old English Sheepdog, Boxer, Maltese, Kuvasz, and Petit Basset Griffon Vendeen. Prevalence was significantly correlated with body weight and was highest in dogs between 2 and 4 years old. Females were significantly more likely to have THAA than were males. Thyroid hormone autoantibodies may falsely increase measured triiodothyronine (T3) and thyroxine (T4) concentrations in dogs; results suggest that T3 concentration may be falsely increased in approximately 57 of 1,000 dogs with hypothyroidism and that T4 concentration may be falsely increased in approximately 17 of 1,000 dogs with hypothyroidism. Results also suggested that dogs of certain breeds were significantly more or less likely to have THAA than were dogs in general.

Gonadal hormone modulation of Δ9-tetrahydrocannabinol-induced antinociception and metabolism in female versus male rats

PubMed Central

Craft, R.M.; Haas, A.E.; Wiley, J.L.; Yu, Z.; Clowers, B.H.

2016-01-01

The gonadal hormones testosterone (T) in adult males and estradiol (E2) in adult females have been reported to modulate behavioral effects of Δ9-tetrahydrocannabinol (THC). This study determined whether activational effects of T and E2 are sex-specific, and whether hormones modulate production of the active metabolite 11-hydroxy-THC (11-OH-THC) and the inactive metabolite 11-nor-9-carboxy-THC (THC-COOH). Adult male and female rats were gonadectomized (GDX) and treated with nothing (0), T (10-mm Silastic capsule/100 g body weight), or E2 (1-mm Silastic capsule/rat). Three weeks later, saline or the cytochrome P450 inhibitor proadifen (25 mg/kg; to block THC metabolism and boost THC's effects) was injected i.p.; one h later, vehicle or THC (3 mg/kg females, 5 mg/kg males) was injected i.p., and rats were tested for antinociceptive and motoric effects 15-240 min post-injection. T did not consistently alter THC-induced antinociception in males, but decreased it in females (tail withdrawal test). Conversely, T decreased THC-induced catalepsy in males, but had no effect in females. E2 did not alter THC-induced antinociception in females, but enhanced it in males. The discrepant effects of T and E2 on males’ and females’ behavioral responses to THC suggests that sexual differentiation of THC sensitivity is not simply due to activational effects of hormones, but also occurs via organizational hormone or sex chromosome effects. Analysis of serum showed that proadifen increased THC levels, E2 increased 11-OH-THC in GDX males, and T decreased 11-OH-THC (and to a lesser extent, THC) in GDX females. Thus, hormone modulation of THC's behavioral effects is caused in part by hormone modulation of THC oxidation to its active metabolite. However, the fact that hormone modulation of metabolism did not alter THC sensitivity similarly on all behavioral measures within each sex suggests that other mechanisms also play a role in gonadal hormone modulation of THC sensitivity in adult

Thyroid Hormone Regulates the Expression of the Sonic Hedgehog Signaling Pathway in the Embryonic and Adult Mammalian Brain

PubMed Central

Desouza, Lynette A.; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E.; Kottmann, Andreas H.; Tole, Shubha

2011-01-01

Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and hyperthyroidism bidirectionally influenced Shh mRNA in embryonic forebrain signaling centers at stages before fetal thyroid hormone synthesis. Further, Smo and Ptc expression were significantly decreased in the forebrain of embryos derived from hypothyroid dams. Adult-onset thyroid hormone perturbations also regulated expression of the Shh pathway bidirectionally, with a significant induction of Shh, Ptc, and Smo after hyperthyroidism and a decline in Smo expression in the hypothyroid brain. Short-term T3 administration resulted in a significant induction of cortical Shh mRNA expression and also enhanced reporter gene expression in Shh+/LacZ mice. Further, acute T3 treatment of cortical neuronal cultures resulted in a rapid and significant increase in Shh mRNA, suggesting direct effects. Chromatin immunoprecipitation assays performed on adult neocortex indicated enhanced histone acetylation at the Shh promoter after acute T3 administration, providing further support that Shh is a thyroid hormone-responsive gene. Our results indicate that maternal and adult-onset perturbations of euthyroid status cause robust and region-specific changes in the Shh pathway in the embryonic and adult forebrain, implicating Shh as a possible mechanistic link for specific neurodevelopmental effects of thyroid hormone. PMID:21363934

Specific visible radiation facilitates lipolysis in mature 3T3-L1 adipocytes via rhodopsin-dependent β3-adrenergic signaling.

PubMed

Park, Phil June; Cho, Jae Youl; Cho, Eun-Gyung

2017-06-01

The regulation of fat metabolism is important for maintaining functional and structural tissue homeostasis in biological systems. Reducing excessive lipids has been an important concern due to the concomitant health risks caused by metabolic disorders such as obesity, adiposity and dyslipidemia. A recent study revealed that unlike conventional care regimens (e.g., diet or medicine), low-energy visible radiation (VR) regulates lipid levels via autophagy-dependent hormone-sensitive lipase (HSL) phosphorylation in differentiated human adipose-derived stem cells. To clarify the underlying cellular and molecular mechanisms, we first verified the photoreceptor and photoreceptor-dependent signal cascade in nonvisual 3T3-L1 adipocytes. For a better understanding of the concomitant phenomena that result from VR exposure, mature 3T3-L1 adipocytes were exposed to four different wavelengths of VR (410, 505, 590 and 660nm) in this study. The results confirmed that specific VR wavelengths, especially 505nm than 590nm, increase intracellular cyclic adenosine monophosphate (cAMP) levels and decrease lipid droplets. Interestingly, the mRNA and protein levels of the Opn2 (rhodopsin) photoreceptor increased after VR exposure in mature 3T3-L1 adipocytes. Subsequent treatment of mature 3T3-L1 adipocytes at a specific VR wavelength induced rhodopsin- and β3-adrenergic receptor (AR)-dependent lipolytic responses that consequently led to increases in intracellular cAMP and phosphorylated HSL protein levels. Our study indicates that photoreceptors are expressed and exert individual functions in nonvisual cells, such as adipocytes. We suggest that the VR-induced photoreceptor system could be a potential therapeutic target for the regulation of lipid homeostasis in a non-invasive manner. Copyright © 2017 Elsevier GmbH. All rights reserved.

3 Tesla magnetic resonance imaging with and without corticotropin releasing hormone stimulation for the detection of microadenomas in Cushing's syndrome.

PubMed

Erickson, Dana; Erickson, Bradley; Watson, Robert; Patton, Alice; Atkinson, John; Meyer, Fredric; Nippoldt, Todd; Carpenter, Paul; Natt, Neena; Vella, Adrian; Thapa, Prabin

2010-06-01

We sought to determine if higher resolution 3 Tesla (T) magnetic resonance imaging (MRI) with or without ovine corticotropin releasing hormone (o-CRH) stimulation would increase the sensitivity for detection of pituitary microadenomas in ACTH-dependent Cushing's syndrome (CS). We prospectively identified 23 patients over a 2-year period with clinical and biochemical evidence of ACTH-dependent CS with no lesion (n = 11) or equivocal lesion (n = 10) on 1.5T MRI. Subsequently, two additional MRIs were performed in random order: 3T nonstimulated MRI or 3T MRI with o-CRH in all patients. Three neuroradiologists reviewed all examinations in a randomized blinded fashion. Patients were divided into four groups, depending on the outcome of their evaluation and treatment for CS. Two patients had to be excluded, and so we report on 21 subjects. Both 3T MRI without (P < 0.016) and with o-CRH stimulation (P < 0.013) was significantly more sensitive for detection of pituitary microadenomas than 1.5T MRI for Group 1 (definitive proof of Cushing's disease, n = 10). Group 2 (those in group 1, plus three patients where dynamic/invasive testing suggested pituitary source) also showed a significant (P < 0.012) advantage for 3T. There was no difference between the 3T and the 3T o-CRH examinations for any of the pulse sequences. We did not observe a statistically significant difference in other patient groups [patients with recurrent CD (n = 6) and patients with ectopic CS (n = 2)]. The results of our prospective blinded studies suggest that 3T MRI of pituitary gland should be considered in evaluation of patients with ACTH-dependent CD when 1.5T imaging is negative or equivocal.

T3 (Triiodothyronine) Test

MedlinePlus

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A thyrotropin-secreting macroadenoma with positive growth hormone and prolactin immunostaining: A case report and literature review.

PubMed

Kuzu, F; Bayraktaroğlu, T; Zor, F; G N, B D; Salihoğlu, Y S; Kalaycı, M

2015-01-01

Thyrotropin (thyroid stimulating hormone [TSH]) secreting pituitary adenomas (TSHoma) are rare adenomas presenting with hyperthyroidism due to impaired negative feedback of thyroid hormone on the pituitary and inappropriate TSH secretion. This article presents a case of TSH-secreting macroadenoma without any clinical hyperthyroidism symptoms accompanying immunoreaction with growth hormone (GH) and prolactin. A 36-year-old female patient was admitted with complaints of irregular menses and blurred vision. On physical exam, she had bitemporal hemianopsia defect. Magnetic resonance imaging (MRI) evaluation showed suprasellar macroadenoma measuring 33 mm × 26 mm × 28 mm was detected on pituitary MRI. She had no hyperthyroidism symptoms clinically. Although free T4 and free T3 levels were elevated, TSH level was inappropriately within the upper limit of normal. Response to T3 suppression and thyrotropin releasing hormone-stimulation test was inadequate. Other pituitary hormones were normal. Transsphenoidal adenomectomy was performed due to parasellar compression findings. Immunohistochemically widespread reaction was observed with TSH, GH and prolactin in the adenoma. The patient underwent a second surgical procedure 2 months later due to macroscopic residual tumor, bitemporal hemianopsia and a suprasellar homogenous uptake with regular borders on indium-111 octreotide scintigraphy. After second surgery; due to ongoing symptoms and residual tumor, she was managed with octreotide and cabergoline treatment. On her follow-up with medical treatment, TSH and free T4 values were within normal limits. Although silent TSHomas are rare, they may arise with compression symptoms as in our case. The differential diagnosis of secondary hyperthyroidism should include TSHomas and thyroid hormone receptor resistance syndrome.

Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

PubMed

Warren, W B; Gurewitsch, E D; Goland, R S

1995-02-01

We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

Contrasting Phenotypes in Resistance to Thyroid Hormone Alpha Correlate with Divergent Properties of Thyroid Hormone Receptor α1 Mutant Proteins.

PubMed

Moran, Carla; Agostini, Maura; McGowan, Anne; Schoenmakers, Erik; Fairall, Louise; Lyons, Greta; Rajanayagam, Odelia; Watson, Laura; Offiah, Amaka; Barton, John; Price, Susan; Schwabe, John; Chatterjee, Krishna

2017-07-01

Resistance to thyroid hormone alpha (RTHα), a disorder characterized by tissue-selective hypothyroidism and near-normal thyroid function tests due to thyroid receptor alpha gene mutations, is rare but probably under-recognized. This study sought to correlate the clinical characteristics and response to thyroxine (T4) therapy in two adolescent RTHα patients with the properties of the THRA mutation, affecting both TRα1 and TRα2 proteins, they harbored. Clinical, auxological, biochemical, and physiological parameters were assessed in each patient at baseline and after T4 therapy. Heterozygous THRA mutations occurring de novo were identified in a 17-year-old male (patient P1; c.788C>T, p.A263V mutation) investigated for mild pubertal delay and in a 15-year-old male (patient P2; c.821T>C, p.L274P mutation) with short stature (0.4th centile), skeletal dysplasia, dysmorphic facies, and global developmental delay. Both individuals exhibited macrocephaly, delayed dentition, and constipation, together with a subnormal T4/triiodothyronine (T3) ratio, low reverse T3 levels, and mild anemia. When studied in vitro, A263V mutant TRα1 was transcriptionally impaired and inhibited the function of its wild-type counterpart at low (0.01-10 nM) T3 levels, with higher T3 concentrations (100 nM-1 μM) reversing dysfunction and such dominant negative inhibition. In contrast, L274P mutant TRα1 was transcriptionally inert, exerting significant dominant negative activity, only overcome with 10 μM of T3. Mirroring this, normal expression of KLF9, a TH-responsive target gene, was achieved in A263V mutation-containing peripheral blood mononuclear cells following 1 μM of T3 exposure, but with markedly reduced expression levels in L274P mutation-containing peripheral blood mononuclear cells, even with 10 μM of T3. Following T4 therapy, growth, body composition, dyspraxia, and constipation improved in P1, whereas growth retardation and constipation in P2 were unchanged

Low concentrations of bisphenol a suppress thyroid hormone receptor transcription through a nongenomic mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheng, Zhi-Guo; Tang, Yuan; Liu, Yu-Xiang

Bisphenol (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Various rodent and in vitro studies have shown that thyroid hormone (TH) function can be impaired by BPA. However, it is still unknown if low concentrations of BPA can suppress the thyroid hormone receptor (TR) transcription. The present study aims to investigate the possible suppressing effects of low concentrations of BPA on TR transcription and the involved mechanism(s) in CV-1 cells derived from cercopithecus aethiops monkey kidneys. Using gene reporter assays, BPA at concentrations as low as 10{sup −9} Mmore » suppresses TR or steroid receptor coactivator-1(SRC-1)-enhanced TR transcription, but not reducing TR/SRC-1 interaction in mammalian two-hybrid and glutathione S-transferase pull-down studies. It has been further shown that both nuclear receptor co-repressor (N-CoR) and silencing mediator for retinoid and thyroid hormone receptors (SMRT) are recruited to the TR-β1 by BPA in the presence of physiologic concentrations of T3 or T4. However, the overexpression of β3 integrin or c-Src significantly reduces BPA-induced recruitment of N-CoR/SMRT to TR or suppression of TR transcription. Furthermore, BPA inhibits the T3/T4-mediated interassociation of the β3 integrin/c-Src/MAPK/TR-β1 pathways by the co-immunoprecipitation. These results indicate that low concentrations of BPA suppress the TR transcription by disrupting physiologic concentrations of T3/T4-mediated β3 integrin/c-Src/MAPK/TR-β1 pathways, followed by recruiting N-CoR/SMRT to TR-β1, providing a novel insight regarding the TH disruption effects of low concentration BPA. -- Highlights: ► Environmentally relevant concentrations of BPA suppress TR transcription. ► BPA recruits the N-CoR/SMRT to TR under the physiologic concentrations of T3/T4. ► BPA disrupts T3/T4-mediated β3 integrin/c-Src/MAPK/TR-β1 pathways.« less

Clinical Consequences of Mutations in Thyroid Hormone Receptor-α1

PubMed Central

van Mullem, Alies A.; Visser, Theo J.; Peeters, Robin P.

2014-01-01

Thyroid hormone (TH) exerts its biological activity via the TH receptors TRα1 and TRβ1/2, which are encoded by the THRA and THRB genes. The first patients with mutations in THRB were identified decades ago. These patients had a clinical syndrome of resistance to TH associated with high serum TH and nonsuppressed thyroid-stimulating hormone levels. Until recently, no patients with mutations in THRA had been identified. In an attempt to predict the clinical phenotype of such patients, different TRα1 mutant mouse models have been generated. These mice have a variable phenotype depending on the location and severity of the mutation. Recently, the first humans with mutations in THRA were identified. Their phenotype consists of relatively low serum T4 and high serum T3 levels (and thus an elevated T3/T4 ratio), growth retardation, delayed mental and bone development, and constipation. While, in retrospect, certain features present in humans can also be found in mouse models, the first humans carrying a defect in TRα1 were not suspected of having a THRA gene mutation initially. The current review focuses on the clinical consequences of TRα1 mutations. PMID:24847461

Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance

PubMed Central

Alvarez-Crespo, Mayte; Csikasz, Robert I.; Martínez-Sánchez, Noelia; Diéguez, Carlos; Cannon, Barbara; Nedergaard, Jan; López, Miguel

2016-01-01

Objective Classically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3) could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice. Methods Wildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry. Results We found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK) and elevated body temperature (0.7 °C). UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY) and agouti-related peptide (AgRP) and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging (“browning”) of inguinal white adipose tissue (iWAT). Conclusions We conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents. PMID:27069867

Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasselgren, P.O.; Chen, I.W.; James, J.H.

Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of /sup 14/C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Txmore » rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis.« less

Biomolecular Doping of Single-Walled Carbon Nanotubes by Thyroid Hormone

NASA Astrophysics Data System (ADS)

Rojas, Enrique; Paulson, Scott; Stern, Mike; Staii, Cristian; Dratman, Mary; Johnson, Alan

2004-03-01

Electron doping of semiconducting single-walled carbon nanotubes (SWNTs) by the thyroid hormone triiodothyronine (T3) is observed. T3 is applied locally, in solution, to SWNT field effect transistors (FETs) and binds along the length of the nanotube. T3 acts as an electron donor, shifting the I-V gate characteristics towards negative values of gate voltage. Shifts in the characteristics are measured as a function of the concentration of the solution. The effect is nearly reversible by rinsing the FETs with the solvent. Several days after application of T3, with no solvent rinsing, the gate characteristics are also nearly reversed. Experiments with a similar molecule for which the phenol ring is brominated as well as experiments with the de-iodinated molecule (T0) are performed to inform the effect of the iodine. The interaction of T3 with SWNTs may suggest a electronic interaction of T3 with other one-dimensional systems such as DNA.

Regulation of Id2 expression in EL4 T lymphoma cells overexpressing growth hormone.

PubMed

Weigent, Douglas A

2009-01-01

In previous studies, we have shown that overexpression of growth hormone (GH) in cells of the immune system upregulates proteins involved in cell growth and protects from apoptosis. Here, we report that overexpression of GH in EL4 T lymphoma cells (GHo) also significantly increased levels of the inhibitor of differentiation-2 (Id2). The increase in Id2 was suggested in both Id2 promoter luciferase assays and by Western analysis for Id2 protein. To identify the regulatory elements that mediate transcriptional activation by GH in the Id2 promoter, promoter deletion analysis was performed. Deletion analysis revealed that transactivation involved a 301-132bp region upstream to the Id2 transcriptional start site. The pattern in the human GHo Jurkat T lymphoma cell line paralleled that found in the mouse GHo EL4 T lymphoma cell line. Significantly less Id2 was detected in the nucleus of GHo EL4 T lymphoma cells compared to vector alone controls. Although serum increased the levels of Id2 in control vector alone cells, no difference was found in the total levels of Id2 in GHo EL4 T lymphoma cells treated with or without serum. The increase in Id2 expression in GHo EL4 T lymphoma cells measured by Id2 promoter luciferase expression and Western blot analysis was blocked by the overexpression of a dominant-negative mutant of STAT5. The results suggest that in EL4 T lymphoma cells overexpressing GH, there is an upregulation of Id2 protein that appears to involve STAT protein activity.

Magnetic storms and variations in hormone levels among residents of North Polar area - Svalbard

NASA Astrophysics Data System (ADS)

Breus, T. K.; Boiko, E. R.; Zenchenko, T. A.

2015-01-01

In the present work four examinations (January, March, June, October 1991-1992) of the blood concentration of adrenal hormones (cortisol) and thyroid hormones (triiodothyronine (T3) and thyroxine T4) and their dependence on space and terrestrial weather parameters have been done for large groups of healthy inhabitants of high latitudes (Svalbard, the most northerly in the world year-round inhabited settlements). The aim of this study was to find the possible sensitivity of these biochemical parameters to variations of external natural factors at high latitudes in three independent groups of people living in this region (miners and people working underground (364 samples), the men working on the ground (274 samples) and women working on the ground (280 samples)). The obtained data indicate that the most expressed dependence of concentration of the three studied hormones is on the level of geomagnetic activity (GMA) - Kp, Ap, Kpmax - 3h. For two of the four seasons (June and October) with increasing levels of GMA a significant (p < 0.05) increase in cortisol concentration in all three independent groups of people was observed. Range of increases in cortisol concentration in different groups were about 30% of the observed variation in the average intragroup concentration in June and from 16% to 38% in October. For T3 dependence was found only in June: drop in hormone secretion with increasing levels of GMA from 18 to 30% of the average range of intragroup variations. Thus it was shown for the first time that at high geographical latitudes with increased level of GMA a significant change in the level of secretion of several hormones leads to the type of adaptive stress reaction.

Analysis of plant hormone profiles in response to moderate dehydration stress.

PubMed

Urano, Kaoru; Maruyama, Kyonoshin; Jikumaru, Yusuke; Kamiya, Yuji; Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2017-04-01

Plant responses to dehydration stress are mediated by highly complex molecular systems involving hormone signaling and metabolism, particularly the major stress hormone abscisic acid (ABA) and ABA-dependent gene expression. To understand the roles of plant hormones and their interactions during dehydration, we analyzed the plant hormone profiles with respect to dehydration responses in Arabidopsis thaliana wild-type (WT) plants and ABA biosynthesis mutants (nced3-2). We developed a procedure for moderate dehydration stress, and then investigated temporal changes in the profiles of ABA, jasmonic acid isoleucine (JA-Ile), salicylic acid (SA), cytokinin (trans-zeatin, tZ), auxin (indole-acetic acid, IAA), and gibberellin (GA 4 ), along with temporal changes in the expression of key genes involved in hormone biosynthesis. ABA levels increased in a bi-phasic pattern (at the early and late phases) in response to moderate dehydration stress. JA-Ile levels increased slightly in WT plants and strongly increased in nced3-2 mutant plants at 72 h after the onset of dehydration. The expression profiles of dehydration-inducible genes displayed temporal responses in an ABA-dependent manner. The early phase of ABA accumulation correlated with the expression of touch-inducible genes and was independent of factors involved in the major ABA regulatory pathway, including the ABA-responsive element-binding (AREB/ABF) transcription factor. JA-Ile, SA, and tZ were negatively regulated during the late dehydration response phase. Transcriptome analysis revealed important roles for hormone-related genes in metabolism and signaling during dehydration-induced plant responses. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Effects of thyroid hormones on the antioxidative status in the uterus of young adult rats

PubMed Central

KONG, Lingfa; WEI, Quanwei; FEDAIL, Jaafar Sulieman; SHI, Fangxiong; NAGAOKA, Kentaro; WATANABE, Gen

2015-01-01

Thyroid hormones and oxidative stress play significant roles in the normal functioning of the female reproductive system. Nitric oxide (NO), a free radical synthesized by nitric oxide synthases (NOS), participates in the regulation of thyroid function and is also a good biomarker for assessment of the oxidative stress status. Therefore, the purpose of this study was to investigate effects of thyroid hormones on uterine antioxidative status in young adult rats. Thirty immature female Sprague-Dawley rats were randomly divided into three groups: control, hypothyroid (hypo-T) and hyperthyroid (hyper-T). The results showed the body weights decreased significantly in both the hypo-T and hyper-T groups and that uterine weights were decreased significantly in the hypo-T group. The serum concentrations of total triiodothyronine (T3) and thyroxine (T4), as well as estradiol (E2), were significantly decreased in the hypo-T group, but increased in the hyper-T group. The progesterone (P4) concentrations in the hypo- and hyperthyroid rats markedly decreased. Immunohistochemistry results provided evidence that thyroid hormone nuclear receptor α/β (TRα/β) and three NOS isoforms were located in different cell types of rat uteri. The NO content and total NOS and inducible NOS (iNOS) activities were markedly diminished in the hypo-T group but increased in the hyper-T group. Moreover, the activities of both glutathione peroxidase (GSH-Px) and catalase (CAT) exhibited significant decreases and increases in the hypo-T and hyper-T groups, respectively. The malondialdehyde (MDA) contents in both the hypo-T and hyper-T groups showed a significant increase. Total superoxide dismutase (T-SOD) activity in the hypo- and hyper-T rats markedly decreased. In conclusion, these results indicated that thyroid hormones have an important influence on the modulation of uterine antioxidative status. PMID:25797533

Comparison of post-contrast 3D-T1-MPRAGE, 3D-T1-SPACE and 3D-T2-FLAIR MR images in evaluation of meningeal abnormalities at 3-T MRI.

PubMed

Jeevanandham, Balaji; Kalyanpur, Tejas; Gupta, Prashant; Cherian, Mathew

2017-06-01

This study was to assess the usefulness of newer three-dimensional (3D)-T 1 sampling perfection with application optimized contrast using different flip-angle evolutions (SPACE) and 3D-T 2 fluid-attenuated inversion recovery (FLAIR) sequences in evaluation of meningeal abnormalities. 78 patients who presented with high suspicion of meningeal abnormalities were evaluated using post-contrast 3D-T 2 -FLAIR, 3D-T 1 magnetization-prepared rapid gradient-echo (MPRAGE) and 3D-T 1 -SPACE sequences. The images were evaluated independently by two radiologists for cortical gyral, sulcal space, basal cisterns and dural enhancement. The diagnoses were confirmed by further investigations including histopathology. Post-contrast 3D-T 1 -SPACE and 3D-T 2 -FLAIR images yielded significantly more information than MPRAGE images (p < 0.05 for both SPACE and FLAIR images) in detection of meningeal abnormalities. SPACE images best demonstrated abnormalities in dural and sulcal spaces, whereas FLAIR was useful for basal cisterns enhancement. Both SPACE and FLAIR performed equally well in detection of gyral enhancement. In all 10 patients, where both SPACE and T 2 -FLAIR images failed to demonstrate any abnormality, further analysis was also negative. The 3D-T 1 -SPACE sequence best demonstrated abnormalities in dural and sulcal spaces, whereas FLAIR was useful for abnormalities in basal cisterns. Both SPACE and FLAIR performed holds good for detection of gyral enhancement. Post-contrast SPACE and FLAIR sequences are superior to the MPRAGE sequence for evaluation of meningeal abnormalities and when used in combination have the maximum sensitivity for leptomeningeal abnormalities. The negative-predictive value is nearly 100%, where no leptomeningeal abnormality was detected on these sequences. Advances in knowledge: Post-contrast 3D-T 1 -SPACE and 3D-T 2 -FLAIR images are more useful than 3D-T 1 -MPRAGE images in evaluation of meningeal abnormalities.

Structural Basis for Prereceptor Modulation of Plant Hormones by GH3 Proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westfall, Corey S.; Zubieta, Chloe; Herrmann, Jonathan

Acyl acid amido synthetases of the GH3 family act as critical prereceptor modulators of plant hormone action; however, the molecular basis for their hormone selectivity is unclear. Here, we report the crystal structures of benzoate-specific Arabidopsis thaliana AtGH3.12/PBS3 and jasmonic acid-specific AtGH3.11/JAR1. These structures, combined with biochemical analysis, define features for the conjugation of amino acids to diverse acyl acid substrates and highlight the importance of conformational changes in the carboxyl-terminal domain for catalysis. We also identify residues forming the acyl acid binding site across the GH3 family and residues critical for amino acid recognition. Our results demonstrate how amore » highly adaptable three-dimensional scaffold is used for the evolution of promiscuous activity across an enzyme family for modulation of plant signaling molecules.« less

Selenium and the control of thyroid hormone metabolism.

PubMed

Köhrle, Josef

2005-08-01

Thyroid hormone synthesis, metabolism and action require adequate availability of the essential trace elements iodine and selenium, which affect homeostasis of thyroid hormone-dependent metabolic pathways. The three selenocysteine-containing iodothyronine deiodinases constitute a novel gene family. Selenium is retained and deiodinase expression is maintained at almost normal levels in the thyroid gland, the brain and several other endocrine tissues during selenium deficiency, thus guaranteeing adequate local and systemic levels of the active thyroid hormone T(3). Due to their low tissue concentrations and their mRNA SECIS elements deiodinases rank high in the cellular and tissue-specific hierarchy of selenium distribution among various selenoproteins. While systemic selenium status and expression of abundant selenoproteins (glutathione peroxidase or selenoprotein P) is already impaired in patients with cancer, disturbed gastrointestinal resorption, unbalanced nutrition or patients requiring intensive care treatment, selenium-dependent deiodinase function might still be adequate. However, disease-associated alterations in proinflammatory cytokines, growth factors, hormones and pharmaceuticals modulate deiodinase isoenzyme expression independent from altered selenium status and might thus pretend causal relationships between systemic selenium status and altered thyroid hormone metabolism. Limited or inadequate supply of both trace elements, iodine and selenium, leads to complex rearrangements of thyroid hormone metabolism enabling adaptation to unfavorable conditions.

Impact of light exposure on thyroid-stimulating hormone results using the Siemens Advia Centaur TSH-3Ultra assay.

PubMed

Armer, Jane; Giles, Diane; Lancaster, Ian; Brownbill, Kathryn

2017-09-01

Background Thyroid-stimulating hormone (TSH) is used as the first-line test of thyroid function. Siemens Healthcare Diagnostics recommend that Siemens Centaur reagents must be protected from light in the assay information and on reagent packaging. We have compared the effect of light exposure on results using Siemens TSH-3Ultra and follicle-stimulating hormone reagents. The thyroid-stimulating hormone reagent includes fluoroscein thiocyanate whereas the follicle-stimulating hormone reagent does not. Methods Three levels of quality controls were analysed using SiemensTSH-3Ultra and follicle-stimulating hormone reagent packs that had been kept protected from light or exposed to light at 6-h intervals for 48 h and then at 96 h. Results Thyroid-stimulating hormone results were significantly lower after exposure of TSH-3Ultra reagent packs to light. Results were >15% lower at all three levels of quality control following 18 h of light exposure and continued to decrease until 96 h. There was no significant difference in follicle-stimulating hormone results whether reagents had been exposed to or protected from light. Conclusions Thyroid-stimulating hormone results but not follicle-stimulating hormone results are lowered after exposure of reagent packs to light. Laboratories must ensure that TSH-3Ultra reagents are not exposed to light and analyse quality control samples on every reagent pack to check that there has not been light exposure prior to delivery. The labelling on TSH-3Ultra reagent packs should reflect the significant effect of light exposure compared with the follicle-stimulating hormone reagent. We propose that the effect of light exposure on binding of fluoroscein thiocyanate to the solid phase antibody causes the falsely low results.

Thyroid hormone fluctuations indicate a thermoregulatory function in both a tropical (Alouatta palliata) and seasonally cold-habitat (Macaca fuscata) primate.

PubMed

Thompson, Cynthia L; Powell, Brianna L; Williams, Susan H; Hanya, Goro; Glander, Kenneth E; Vinyard, Christopher J

2017-11-01

Thyroid hormones boost animals' basal metabolic rate and represent an important thermoregulatory pathway for mammals that face cold temperatures. Whereas the cold thermal pressures experienced by primates in seasonal habitats at high latitudes and elevations are often apparent, tropical habitats also display distinct wet and dry seasons with modest changes in thermal environment. We assessed seasonal and temperature-related changes in thyroid hormone levels for two primate species in disparate thermal environments, tropical mantled howlers (Alouatta palliata), and seasonally cold-habitat Japanese macaques (Macaca fuscata). We collected urine and feces from animals and used ELISA to quantify levels of the thyroid hormone triiodothyronine (fT 3 ). For both species, fT 3 levels were significantly higher during the cooler season (wet/winter), consistent with a thermoregulatory role. Likewise, both species displayed greater temperature deficits (i.e., the degree to which animals warm their body temperature relative to ambient) during the cooler season, indicating greater thermoregulatory pressures during this time. Independently of season, Japanese macaques displayed increasing fT 3 levels with decreasing recently experienced maximum temperatures, but no relationship between fT 3 and recently experienced minimum temperatures. Howlers increased fT 3 levels as recently experienced minimum temperatures decreased, although demonstrated the opposite relationship with maximum temperatures. This may reflect natural thermal variation in howlers' habitat: wet seasons had cooler minimum and mean temperatures than the dry season, but similar maximum temperatures. Overall, our findings support the hypothesis that both tropical howlers and seasonally cold-habitat Japanese macaques utilize thyroid hormones as a mechanism to boost metabolism in response to thermoregulatory pressures. This implies that cool thermal pressures faced by tropical primates are sufficient to invoke an

Impact of Triclosan on Female Reproduction through Reducing Thyroid Hormones to Suppress Hypothalamic Kisspeptin Neurons in Mice.

PubMed

Cao, Xin-Yuan; Hua, Xu; Xiong, Jian-Wei; Zhu, Wen-Ting; Zhang, Jun; Chen, Ling

2018-01-01

Triclosan (TCS), a broad-spectrum antimicrobial agent, is widely used in clinical settings and various personal care products. The aim of this study was to evaluate the influence of TCS on reproductive endocrine and function. Here, we show that the exposure of adult female mice to 10 or 100 mg/kg/day TCS caused prolongation of diestrus, and decreases in antral follicles and corpora lutea within 2 weeks. TCS mice showed decreases in the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone, and gonadotrophin-releasing hormone ( GnRH ) mRNA with the lack of LH surge and elevation of prolactin (PRL). TCS mice had lower kisspeptin immunoreactivity and kiss1 mRNA in anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Moreover, the estrogen (E2)-enhanced AVPV-kisspeptin expression was reduced in TCS mice. In addition, the serum thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) in TCS mice were reduced with increases in levels of thyroid stimulating hormone (TSH) and thyroid releasing hormone (TRH). In TCS mice, the treatment with Levothyroxine (L-T4) corrected the increases in PRL, TSH and TRH; the administration of L-T4 or type-2 dopamine receptors agonist quinpirole inhibiting PRL release could rescue the decline of kisspeptin expression in AVPV and ARC; the treatment with L-T4, quinpirole or the GPR45 agonist kisspeptin-10 recovered the levels of serum LH and FSH and progesterone, and GnRH mRNA. Furthermore, TCS mice treated with L-T4 or quinpirole resumed regular estrous cycling, follicular development and ovulation. Together, these results indicate that exposing adult female mice to TCS (≥10 mg/kg) reduces thyroid hormones causing hyperprolactinemia that then suppresses hypothalamic kisspeptin expression, leading to deficits in reproductive endocrine and function.

Impact of Triclosan on Female Reproduction through Reducing Thyroid Hormones to Suppress Hypothalamic Kisspeptin Neurons in Mice

PubMed Central

Cao, Xin-Yuan; Hua, Xu; Xiong, Jian-Wei; Zhu, Wen-Ting; Zhang, Jun; Chen, Ling

2018-01-01

Triclosan (TCS), a broad-spectrum antimicrobial agent, is widely used in clinical settings and various personal care products. The aim of this study was to evaluate the influence of TCS on reproductive endocrine and function. Here, we show that the exposure of adult female mice to 10 or 100 mg/kg/day TCS caused prolongation of diestrus, and decreases in antral follicles and corpora lutea within 2 weeks. TCS mice showed decreases in the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone, and gonadotrophin-releasing hormone (GnRH) mRNA with the lack of LH surge and elevation of prolactin (PRL). TCS mice had lower kisspeptin immunoreactivity and kiss1 mRNA in anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Moreover, the estrogen (E2)-enhanced AVPV-kisspeptin expression was reduced in TCS mice. In addition, the serum thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) in TCS mice were reduced with increases in levels of thyroid stimulating hormone (TSH) and thyroid releasing hormone (TRH). In TCS mice, the treatment with Levothyroxine (L-T4) corrected the increases in PRL, TSH and TRH; the administration of L-T4 or type-2 dopamine receptors agonist quinpirole inhibiting PRL release could rescue the decline of kisspeptin expression in AVPV and ARC; the treatment with L-T4, quinpirole or the GPR45 agonist kisspeptin-10 recovered the levels of serum LH and FSH and progesterone, and GnRH mRNA. Furthermore, TCS mice treated with L-T4 or quinpirole resumed regular estrous cycling, follicular development and ovulation. Together, these results indicate that exposing adult female mice to TCS (≥10 mg/kg) reduces thyroid hormones causing hyperprolactinemia that then suppresses hypothalamic kisspeptin expression, leading to deficits in reproductive endocrine and function. PMID:29403355

Variability of Hormonal Stress Markers Collected from a Managed Dolphin Population

DTIC Science & Technology

2011-09-30

physiological indicators of stress in wild marine mammals and the interrelationships between different stress markers can be used to estimate the impact of...samples will be processed for adrenocorticosteroids (ACTH, cortisol, aldosterone ), catecholamines (epinephrine, norepinephrine), and thyroid hormones...T3 and T4) via radioimmunoassay (RIA). Radioimmunoassay methods have previously been validated for cortisol and aldosterone in this species (Houser

Lipid profile and thyroid hormone status in the last trimester of pregnancy in single-humped camels (Camelus dromedarius).

PubMed

Omidi, Arash; Sajedi, Zhila; Montazer Torbati, Mohammad Bagher; Ansari Nik, Hossein

2014-04-01

Changes in lipid metabolism have been shown to occur during pregnancy. The thyroid hormones affect lipid metabolism. The present study was carried out to find out whether the last trimester of pregnancy affects thyroid hormones, thyroid-stimulating hormone (TSH), lipid, and lipoprotein profile in healthy dromedary camels. Twenty clinical healthy dromedary camels aged between 4-5 years were divided into two equal groups: (1) pregnant camels in their last trimester of pregnancy and (2) non-pregnant age-matched controls. Thyroid function tests were carried out by measuring serum levels of TSH, free thyroxin (fT4), total thyroxin (T4), free triiodothyronine (fT3), and total triiodothyronine (T3) by commercially available radio immunoassay kits. Total cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL) cholesterol were analyzed using enzymatic/spectrophotometric methods while low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL), and total lipid (TL) were calculated using Friedewald's and Raylander's formula, respectively. Serum levels of TSH and thyroid hormones except fT4 did not show any significant difference between pregnant and non-pregnant camels. fT4 level was lower in the pregnant camels (P < 0.05). Serum levels of total cholesterol, triglyceride, total lipid, LDL cholesterol, HDL cholesterol, and VLDL did not show significant difference between pregnant and non-pregnant camels. All of these variables in pregnant camels were higher than non-pregnant. Based on the results of this study, the fetus load may not alter the thyroid status of the camel and the concentrations of thyroid hormones were not correlated with TSH and lipid profile levels in the healthy pregnant camels.

COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem-Cell Model of Cortical Pyramidal Neuronal Differentiation.

PubMed

Teng, Xiaochun; Liu, Yan-Yun; Teng, Weiping; Brent, Gregory A

2018-05-01

Thyroid hormone is critical for normal brain development and acts in a spatial and temporal specific pattern. Thyroid hormone excess, or deficiency, can lead to irreversible impairment of brain and sensory development. Chicken ovalbumin upstream-transcription factor 1 (COUP-TF1), expressed early in neuronal development, is essential to achieve normal brain structure. Thyroid hormone stimulation of gene expression is inversely correlated with the level of COUP-TF1 expression. An in vitro method of differentiating mouse embryonic stem (mES) cells into cortical neurons was utilized to study the influence of COUP-TF1 on thyroid hormone signaling in brain development. mES cells were cultured and differentiated in specific conditioned media, and a high percentage of nestin-positive progenitor neurons in the first stage, and cortical neurons in the second stage, was obtained with characteristic neuronal firing. The number of nestin-positive progenitors, as determined by fluorescence-activated cell sorting analysis, was significantly greater with triiodothyronine (T3) treatment compared to control (p < 0.05). T3 enhanced the expression of cortical neuron marker (Tbr1 and Rc3) mRNAs. After COUP-TF1 knockdown, the number of nestin-positive progenitors was reduced compared to control (p < 0.05), but the number increased with T3 treatment. The mRNA of cortical neuronal gene markers was measured after COUP-TF1 knockdown. In the presence of T3, the peak expression of neuron markers Emx1, Tbr1, Camkiv, and Rc3 mRNA was earlier, at day 18 of differentiation, compared to control cells, at day 22. Furthermore, after COUP-TF1 knockdown, T3 induction of Rc3 and Tbr1 mRNA was significantly enhanced compared to cells expressing COUP-TF1. These results indicate that COUP-TF1 plays an important role in modulating the timing and magnitude of T3-stimulated gene expression required for normal corticogenesis.

Ectopic bone formation and chondrodysplasia in transgenic mice carrying the rat C3(1)/T{sub AG} fusion gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, J.E.; Maroulakou, I.G.; Anver, M.

Transgenic mice expressing the SV40 large T-antigen (T{sup AG}) under the regultory control of the hormone-responsive rat C3(1) prostatein promoter develop unusual bone and cartilage lesions, as well as ectopic bone and cartilage formation. Two lines of transgenic animals have been propagated in which the expression of the transgene in chondrocytes results in a mild to moderate generalized disorganization of cartilage growth which appears to affect multiple tissues, including the trachea, ear pinna and articular cartilage. The epiphyseal plates are also affected with normal architecture of the zones of proliferation and maturation, but marked elongation of the zone of hypertrophy.more » Immunocytochemistry demonstrates that expression of T{sup AG} is limited to the zone of hypertropny in the epiphyseal plates, suggesting that the chondrocytes become hormone-responsive at this particular stage of differentiation. Normal mineralization and trabecular formation in long bone appears to occur. Ectopic bone and cartilage formation occurs in the foot pads of the fore- and hind- feet over the course of several months. This is preceded by proliferation of sweat gland epithelial cells followed by the appearance of nodules of cartilage and bone. The nodules are closely associated with proliferating epithelium but are not contiguous with bony structures normally found in the feet. The roles of BMP`s, growth factors, oncogenes and hormones in the development of these lesions will be presented. These transgenic animals may provide new insights into hormone-responsiveness of chondrocytes, as well as factors involved in the processes of bone and cartilage differentiation and growth. These transgenic animals may serve as a useful model for human heterotopic bone formation.« less

Anti-Müllerian Hormone and Inhibin-A, but not Inhibin-B or Insulin-Like Peptide-3, may be Used as Surrogates in the Diagnosis of Polycystic Ovary Syndrome in Adolescents: Preliminary Results.

PubMed

Yetim, Aylin; Yetim, Çağcıl; Baş, Firdevs; Erol, Oğuz Bülent; Çığ, Gülnaz; Uçar, Ahmet; Darendeliler, Feyza

2016-09-01

Polycystic ovary syndrome (PCOS) is a common endocrine problem in adolescents with an increasing prevalence of 30%. Pursuing new biomarkers with high specificity and sensitivity in the diagnosis of PCOS in adolescents is currently an active area of research. We aimed to investigate the diagnostic value of anti-Müllerian hormone (AMH), insulin-like peptide-3 (INSL3), inhibin-A (INH-A), and inhibin-B (INH-B) in adolescents with PCOS and also to determine the association, if any, between these hormones and clinical/laboratory findings related with hyperandrogenism. The study group comprised 53 adolescent girls aged between 14.5 and 20 years who were admitted to our outpatient clinic with symptoms of hirsutism and/or irregular menses and diagnosed as having PCOS in accordance with the Rotterdam criteria. Twenty-six healthy peers, eumenorrheic for at least two years and body mass index-matched, constituted the controls. Fasting blood samples for hormones [luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone-sulfate (DHEAS), androstenedione (D4-A), total/free testosterone (T/fT), sex hormone binding globulin (SHBG), AMH, INSL3, INH-A, INH-B] were drawn after an overnight fast. In the PCOS group, 83% of the subjects were oligomenorrheic/amenorrheic and 87% had hirsutism. The LH, LH/FSH ratio, total T, fT, free androgen-index (FAI), DHEAS levels were significantly higher (p=0.005, p=0.042, p=0.047, p<0.001, p=0.007, p=0.014, respectively) and SHBG was significantly lower (p=0.004) in PCOS patients as compared to the controls. Although the INSL-3 and INH-B levels showed no difference between the groups (p>0.05), AMH and INH-A levels were found to be significantly higher in the PCOS group compared to the controls (p<0.001, p<0.001, respectively). In multiple linear regression analysis, WC SDS (p=0.028), logD4-A (p=0.033), logSHBG (p=0.031), and total ovarian volume (p=0.045) had significant effects on AMH levels, and LH (p=0.003) on INH

A nonpeptidyl growth hormone secretagogue.

PubMed

Smith, R G; Cheng, K; Schoen, W R; Pong, S S; Hickey, G; Jacks, T; Butler, B; Chan, W W; Chaung, L Y; Judith, F

1993-06-11

A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.

Relation of thyroid hormone abnormalities with subclinical inflammatory activity in patients with type 1 and type 2 diabetes mellitus.

PubMed

Moura Neto, Arnaldo; Parisi, Maria Candida Ribeiro; Alegre, Sarah Monte; Pavin, Elizabeth Joao; Tambascia, Marcos Antonio; Zantut-Wittmann, Denise Engelbrecht

2016-01-01

Thyroid hormone (TH) abnormalities are common in patients with diabetes mellitus (DM). These thyroid hormone abnormalities have been associated with inflammatory activity in several conditions but this link remains unclear in DM. We assessed the influence of subclinical inflammation in TH metabolism in euthyroid diabetic patients. Cross-sectional study involving 258 subjects divided in 4 groups: 70 patients with T2DM and 55 patients with T1DM and two control groups of 70 and 63 non-diabetic individuals, respectively. Groups were paired by age, sex, and body mass index (BMI). We evaluated the association between clinical and hormonal variables [thyrotropin, reverse T3 (rT3), total and free thyroxine (T4), and triiodothyronine (T3)] with the inflammation markers C-reactive protein (hs-CRP), serum amyloid A (SAA), and interleukin-6 (IL-6). Serum T3 and free T3 were lower in patients with diabetes (all P < 0.001) compared to the control groups. Interleukin-6 showed positive correlations with rT3 in both groups (P < 0.05). IL-6 was independently associated to FT3/rT3 (B = -0.193; 95% CI -0.31; -0.076; P = 0.002) and FT4/rT3 (B = -0.107; 95% CI -0.207; -0.006; P = 0.039) in the T1DM group. In the T2DM group, SAA (B = 0.18; 95% CI 0.089; 0.271; P < 0.001) and hs-CRP (B = -0.069; 95% CI -0.132; -0.007; P = 0.03) predicted FT3 levels. SAA (B = -0.16; 95% CI -0.26; -0.061; P = 0.002) and IL6 (B = 0.123; 95% CI 0.005; 0.241; P = 0.041) were related to FT4/FT3. In DM, differences in TH levels compared to non-diabetic individuals were related to increased subclinical inflammatory activity and BMI. Altered deiodinase activity was probably involved. These findings were independent of sex, age, BMI, and HbA1c levels.

Evaluation of two over-the-counter natural thyroid hormone preparations in human volunteers.

PubMed

Csako, G; Corso, D M; Kestner, J; Bokser, A D; Kennedy, P E; Pucino, F

1992-04-01

To determine the pharmacologic activity of over-the-counter (OTC) thyroid preparations. In vitro analysis and a prospective, crossover study in vivo. Tertiary care center. Two healthy adult volunteers. Three OTC preparations (Thyrotrophin PMG [bovine thyroid PMG extract], Thyro Forte [thyroid lymphogland concentrate with synergistic complex], and Thyro Complex [thyroid lyophilized gland concentrate with synergistic complex]) were analyzed in vitro. Volunteers were administered two times the manufacturer's maximum recommended daily dose of either Thyrotrophin PMG or Thyro Forte for one week, washed out for four to five weeks, and crossed over to receive the opposite tablet preparation for an additional week. The triiodothyronine (T3) and thyroxine (T4) contents of OTC preparations were measured by HPLC. Vital signs, serum total and free T4, total T3, thyroid stimulating hormone, thyroxine binding globulin, thyroglobulin, and general chemistry tests (including glucose and cholesterol) were monitored before, during, and between administration of the products. HPLC analysis of the three OTC preparations showed no T4 but did show possible T3 in two of these products. We found no definite clinical or laboratory evidence of thyroid hormone excess with either product. Healthcare professionals should advise against the use of these scientifically unsound and relatively expensive OTC thyroid preparations, of which the therapeutic efficacy is unknown.

The use of konjac glucomannan to lower serum thyroid hormones in hyperthyroidism.

PubMed

Azezli, Adil Dogan; Bayraktaroglu, Taner; Orhan, Yusuf

2007-12-01

Patients with hyperthyroidism occasionally need rapid restoration to the euthyroid state. In view of the increased enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) in thyrotoxicosis, and metabolic effects of konjac glucomannan in gastrointestinal system, we aimed to determine the activity of glucomannan in treatment of hyperthyroidism. A prospective, randomized, placebo-controlled, one-blind study design was used with newly diagnosed 48 hyperthyroid patients (30 patients with Graves' disease and 12 with multinodulary goitre). They were assigned to one of the following treatment groups: I) methimazole 2 x 10 mg, propranolol 2 x 20 mg, and glucomannan (Propol) 2 x 1.3 gr daily for two months; II) methimazole 2 x 10 mg, propranolol 2 x 20 mg, and placebo powder daily for two months. No differences were detected from the point of view of the baseline thyroid hormone levels between groups (p > 0.05). Further analyses revealed that the patients receiving glucomannan at the end of the second, fourth and sixth weeks of the study had significantly lower serum T3, T4, FT3 and FT4 levels than the patients who received placebo (p < 0.05). TSH was not different between the two groups at any specific time (p > 0.05). At week 8, thyroid hormone levels were not shown any differences. The glucomannan-treated group had a more rapid decline in all four serum thyroid hormone levels than the placebo-treated group. We believe our preliminary results indicate that glucomannan may be a safe and easily tolerated adjunctive therapeutic agent in the treatment of thyrotoxicosis. This combination therapy seems most effect during first weeks of treatment of a hyperthyroid patient.

Usefulness of Serum Triiodothyronine (T3) to Predict Outcomes in Patients Hospitalized With Acute Heart Failure.

PubMed

Rothberger, Gary D; Gadhvi, Sonya; Michelakis, Nickolaos; Kumar, Amit; Calixte, Rose; Shapiro, Lawrence E

2017-02-15

Thyroid hormone plays an important role in cardiac function. Low levels of serum triiodothyronine (T 3 ) due to nonthyroidal illness syndrome may have adverse effects in heart failure (HF). This study was designed to assess the ability of T 3 to predict in-hospital outcomes in patients with acute HF. In total, 137 patients without thyroid disease or treatment with drugs which affect TH levels, who were hospitalized with acute HF were prospectively enrolled and studied. TH levels were tested upon hospital admission, and outcomes were compared between patients with low (<2.3 pg/ml) and normal (≥2.3 pg/ml) free T 3 levels as well as between those with low (<0.6 ng/ml) and normal (≥0.6 ng/ml) total T 3 levels. Low free T 3 correlated with an increased length of stay in the hospital (median 11 vs 7 days, p <0.001) and higher rates of intensive care unit admission (31.8% vs 16.9%, p = 0.047), with a trend toward increased need for invasive mechanical ventilation (9.0% vs 1.4%, p = 0.056). Low total T3 correlated with an increased length of stay in the hospital (median 11 vs 7 days, p <0.001) and increased need for invasive mechanical ventilation (9.8% vs 1.3%, p = 0.045). In conclusion, low T 3 predicts worse hospital outcomes in patients with acute HF and can be useful in the risk stratification of these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

[The influence of hypothyroidism on the conversion and binding of thyroid hormones in patients with end-stage renal disease].

PubMed

Dubczak, Iwanna; Niemczyk, Longin; Bartoszewicz, Zbigniew; Szamotulska, Katarzyna; Saracyn, Marek; Niemczyk, Stanisław

2017-03-21

Hypothyroidism in patients with renal failure (RF) causes many metabolic and clinical problems, and both these diseases can mutually exacerbate their disturbances. The aim of this study was to evaluate the effect of hypothyroidism, and end-stage renal disease (ESRD) on conversion of thyroid hormones (TH) in patients with ESRD treated with chronic hemodialysis (HD). The study was performed in 74 patients, including 41 women (K) and 33 men (M) aged 28-83 y.o. in 4 groups: G1 - 12 people with ESRD treated with HD and with newly diagnosed hypothyroidism without substitution (6 K and M 6) aged 66,83±12,90 y.o., G2 - 26 patients with ESRD treated with HD without hypothyroidism (10 F, 16 M) aged 58,85±15,52 y.o., G3 - 11 hypothyroid patients without RF (9 K, 2 M) aged 54,73±21,26 y.o., G4 - 25-persons from control group of healthy subjects (16 M, 9 M) aged 51,24±12,58 y.o. In all subjects the concentration of TSH and TH (T4, T3, fT4, TSH, FT3, rT3) were measured and values of conversion factors (T3/T4, FT3/ fT4, rT3/fT4 and rT3/fT3) and binding TH to protein factors (fT4/T4 and fT3/T3) were calculated. Lower concentration of T3 (p=0.012), fT3 (p<0.001) i fT4 (p=0.014) was found in patients without hypothyroidism than in healthy subjects. Renal failure with concomitant hypothyroidism intensify the disturbances of T4 to T3 conversion (p=0.034) and hypothyroidism with concomitant renal failure disrupts binding of T3 to proteins (p=0.001). FT3 to fT4 ratio in renal failure with concomitant hypothyroidism group was significantly lower than in each other group. rT3 concentrations were the highest in healthy subjects. Concomitance of hypothyroidism and end-stage renal disease reduces the conversion of thyroxine to triiodothyronine, but does not increase the production of rT3. Hypothyroidism significantly increases the disorders of thyroid hormones in end-stage renal disease. There is decreased tendency to bind of thyroid hormone to protein in hypothyroidism in patients with

Hormonal changes after localized prostate cancer treatment. Comparison between external beam radiation therapy and radical prostatectomy.

PubMed

Planas, J; Celma, A; Placer, J; Maldonado, X; Trilla, E; Salvador, C; Lorente, D; Regis, L; Cuadras, M; Carles, J; Morote, J

2016-11-01

To determine the influence of radical prostatectomy (RP) and external beam radiation therapy (EBRT) on the hypothalamic pituitary axis of 120 men with clinically localized prostate cancer treated with RP or EBRT exclusively. 120 patients with localized prostate cancer were enrolled. Ninety two patients underwent RP and 28 patients EBRT exclusively. We measured serum levels of luteinizing hormone, follicle stimulating hormone (FSH), total testosterone (T), free testosterone, and estradiol at baseline and at 3 and 12 months after treatment completion. Patients undergoing RP were younger and presented a higher prostate volume (64.3 vs. 71.1 years, p<0.0001 and 55.1 vs. 36.5 g, p<0.0001; respectively). No differences regarding serum hormonal levels were found at baseline. Luteinizing hormone and FSH levels were significantly higher in those patients treated with EBRT at three months (luteinizing hormone 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p<0,0001) while T and free testosterone levels were significantly lower (T 360,3 vs. 414,83ng/dl, p 0,039; free testosterone 5,94 vs. 7,5pg/ml, p 0,018). At 12 months FSH levels remained significantly higher in patients treated with EBRT compared to patients treated with RP (21,01 vs. 8,51 U/l, p<0,001) while T levels remained significantly lower (339,89 vs. 402,39ng/dl, p 0,03). Prostate cancer treatment influences the hypothalamic pituitary axis. This influence seems to be more important when patients with prostate cancer are treated with EBRT rather than RP. More studies are needed to elucidate the role that prostate may play as an endocrine organ. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Asprosin, a fasting-induced glucogenic protein hormone

USDA-ARS?s Scientific Manuscript database

Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is t...

KM3NeT

NASA Astrophysics Data System (ADS)

de Jong, M.

2015-07-01

KM3NeT is a large research infrastructure, that will consist of a network of deep-sea neutrino telescopes in the Mediterranean Sea. The main objective of KM3NeT is the discovery and subsequent observation of high-energy neutrino sources in the Universe. A further physics perspective is the measurement of the mass hierarchy of neutrinos. A corresponding study, ORCA, is ongoing within KM3NeT. A cost effective technology for (very) large water Cherenkov detectors has been developed based on a new generation of low price 3-inch photo-multiplier tubes. Following the successful deployment and operation of two prototypes, the construction of the KM3NeT research infrastructure has started. The prospects of the different phases of the implementation of KM3NeT are summarised.

Effects of sinensetin on lipid metabolism in mature 3T3-L1 adipocytes.

PubMed

Kang, Seong-Il; Shin, Hye-Sun; Ko, Hee-Chul; Kim, Se-Jae

2013-01-01

Sinensetin is a rare polymethoxylated flavone found in certain citrus fruits. In this study, we investigated the effects of sinensetin on lipid metabolism in mature 3T3-L1 adipocytes. Sinensetin decreased the expression of sterol regulatory element-binding protein 1c (SREBP1c), suggesting its antiadipogeneic property via downreguation of SREBP1c. Also, sinensetin increased the phosphorylation of protein kinase A and hormone-sensitive lipase, indicating its lipolytic property via a cAMP-mediated signaling pathway. Moreover, sinensetin inhibited insulin-stimulated glucose uptake by decreasing the phosphorylation of insulin receptor substrate and Akt. Furthermore, sinensetin increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. It also upregulated mRNA expression of carnitine palmitoyltransferase-1a, suggesting that sinensetin enhances fatty acid β-oxidation through the AMPK pathway. Taken together, these results suggest that sinensetin may have potential as a natural agent for prevention/improvement of obesity. Copyright © 2012 John Wiley & Sons, Ltd.

Differences in primary cellular factors influencing the metabolism and distribution of 3,5,3′-L-triiodothyronine and L-thyroxine

PubMed Central

Oppenheimer, Jack H.; Schwartz, Harold L.; Shapiro, Harvey C.; Bernstein, Gerald; Surks, Martin I.

1970-01-01

Administration of phenobarbital, which acts exclusively on cellular sites, results in an augmentation of the liver/plasma concentration ratio of L-thyroxine (T4) in rats but no change in the liver/plasma concentration ratio of L-triiodothyronine (T3). Whereas phenobarbital stimulates the fecal clearance rate both of T3 and T4, it increases the deiodinative clearance rate of T4 only. These findings suggest basic differences in the cellular metabolism of T3 and T4. Further evidence pointing to cellular differences was obtained from a comparison of the distribution and metabolism of these hormones with appropriate corrections for the effect of differential plasma binding. The percentage of total exchangeable cellular T4 within the liver (28.5) is significantly greater than the corresponding percentage of exchangeable cellular T3 within this organ (12.3). Extrahepatic tissues bind T3 twice as firmly as T4. The cellular metabolic clearance rate (= free hormone clearance rate) of T3 exceeds that of T4 by a factor 1.8 in the rat. The corresponding ratio in man, 2.4, was determined by noncompartmental analysis of turnover studies in four individuals after the simultaneous injection of T4-125I and T3-131I. The greater cellular metabolic clearance rate of T3 both in rat and man may be related to the higher specific hormonal potency of this iodothyronine. PMID:5441537

Magnetic storms and variations in hormone levels among residents of North Polar area--Svalbard.

PubMed

Breus, T K; Boiko, E R; Zenchenko, T A

2015-01-01

In the present work four examinations (January, March, June, October 1991-1992) of the blood concentration of adrenal hormones (cortisol) and thyroid hormones (triiodothyronine (T3) and thyroxine T4) and their dependence on space and terrestrial weather parameters have been done for large groups of healthy inhabitants of high latitudes (Svalbard, the most northerly in the world year-round inhabited settlements). The aim of this study was to find the possible sensitivity of these biochemical parameters to variations of external natural factors at high latitudes in three independent groups of people living in this region (miners and people working underground (364 samples), the men working on the ground (274 samples) and women working on the ground (280 samples)). The obtained data indicate that the most expressed dependence of concentration of the three studied hormones is on the level of geomagnetic activity (GMA) - Kp, Ap, Kpmax - 3h. For two of the four seasons (June and October) with increasing levels of GMA a significant (p<0.05) increase in cortisol concentration in all three independent groups of people was observed. Range of increases in cortisol concentration in different groups were about 30% of the observed variation in the average intragroup concentration in June and from 16% to 38% in October. For T3 dependence was found only in June: drop in hormone secretion with increasing levels of GMA from 18 to 30% of the average range of intragroup variations. Thus it was shown for the first time that at high geographical latitudes with increased level of GMA a significant change in the level of secretion of several hormones leads to the type of adaptive stress reaction. Copyright © 2014 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

KM3NeT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jong, M. de; Leiden Institute of Physics, Leiden University, Leiden; Collaboration: KM3NeT Collaboration

2015-07-15

KM3NeT is a large research infrastructure, that will consist of a network of deep-sea neutrino telescopes in the Mediterranean Sea. The main objective of KM3NeT is the discovery and subsequent observation of high-energy neutrino sources in the Universe. A further physics perspective is the measurement of the mass hierarchy of neutrinos. A corresponding study, ORCA, is ongoing within KM3NeT. A cost effective technology for (very) large water Cherenkov detectors has been developed based on a new generation of low price 3-inch photo-multiplier tubes. Following the successful deployment and operation of two prototypes, the construction of the KM3NeT research infrastructure hasmore » started. The prospects of the different phases of the implementation of KM3NeT are summarised.« less

Hormonal correlates of male life history stages in wild white-faced capuchin monkeys (Cebus capucinus)

PubMed Central

Jack, Katharine M.; Schoof, Valérie A.M.; Sheller, Claire R.; Rich, Catherine I.; Klingelhofer, Peter P.; Ziegler, Toni E.; Fedigan, Linda

2014-01-01

Much attention has been paid to hormonal variation in relation to male dominance status and reproductive seasonality, but we know relatively little about how hormones vary across life history stages. Here we examine fecal testosterone (fT), dihydrotestosterone (fDHT), and glucocorticoid (fGC) profiles across male life history stages in wild white-faced capuchins (Cebus capucinus). Study subjects included 37 males residing in three habituated social groups in the Área de Conservacíon Guanacaste, Costa Rica. Male life history stages included infant (0 to <12 months; N = 3), early juvenile (1 to <3 years; N = 10), late juvenile (3 to <6 years; N = 9), subadult (6 to <10 years; N = 8), subordinate adult (≥10 years; N = 3), and alpha adult (≥ 10 years; N = 4, including one recently deposed alpha). Life history stage was a significant predictor of fT; levels were low throughout the infant and juvenile phases, doubled in subadult and subordinate adults, and were highest for alpha males. Life history stage was not a significant predictor of fDHT, fDHT:fT, or fGC levels. Puberty in white-faced capuchins appears to begin in earnest during the subadult male phase, indicated by the first significant rise in fT. Given their high fT levels and exaggerated secondary sexual characteristics, we argue that alpha adult males represent a distinctive life history stage not experienced by all male capuchins. This study is the first to physiologically validate observable male life history stages using patterns of hormone excretion in wild Neotropical primates, with evidence for a strong association between fT levels and life history stage. PMID:24184868

Interconnection between thyroid hormone signalling pathways and parvovirus cytotoxic functions.

PubMed Central

Vanacker, J M; Laudet, V; Adelmant, G; Stéhelin, D; Rommelaere, J

1993-01-01

Nonstructural (NS) proteins of autonomous parvoviruses can repress expression driven by heterologous promoters, an activity which thus far has not been separated from their cytotoxic effects. It is shown here that, in transient transfection assays, the NS-1 protein of the parvovirus minute virus of mice (MVMp) activates the promoter of the human c-erbA1 gene, encoding the thyroid hormone (T3) receptor alpha. The endogenous c-erbA1 promoter is also a target for induction upon MVMp infection. Moreover, T3 was found to up-modulate the level of cell sensitivity to parvovirus attack. These data suggest an interconnection between T3 signalling and NS cytotoxic pathways. Images PMID:8230488

Reproductive Hormones and Their Receptors May Affect Lung Cancer.

PubMed

Dou, Mengmeng; Zhu, Keyan; Fan, Zhirui; Zhang, Yuxuan; Chen, Xiufang; Zhou, Xueliang; Ding, Xianfei; Li, Lifeng; Gu, Zhaosen; Guo, Maofeng; Yan, Ming; Deng, Xiaoming; Shen, Peihong; Wang, Shuling

2017-01-01

In contrast to men, women have experienced a rapid increase in lung cancer mortality. Numerous studies have found that the sex differences in lung cancer are due to reproductive hormones. Experiments in female mice with and without ovariectomy were performed to explore the possible mechanism by which sex hormones (and their receptors) influence lung cancer. Twenty-four female C57BL/6 mice aged 56-62 days were randomly divided into the ovariectomized group and the control group. In the ovariectomized group, the bilateral ovaries were removed via the dorsal approach, while the control group underwent a sham operation with bilateral ovarian fat resection at the same sites. After 3 weeks of recovery, Lewis lung cancer cells were transplanted into these mice by subcutaneous inoculation of a tumour cell suspension to establish the ovariectomized lung cancer model. Beginning on the 6th day after subcutaneous inoculation, mouse weight and transplanted tumour volume were measured every 3 days. After 3 weeks, all the mice were killed by cervical dislocation, and we measured the tumour weight. Mouse serum and tumour tissues were removed. Then, the serum levels of E2 (oestradiol) and T (testosterone) were detected by ELISA; the protein expression levels of AR (androgen receptor), ERα (oestrogen receptor α) and ERβ (oestrogen receptor β) were detected by Western Blot and IHC (immunohistochemistry); and the mRNA expression levels of AR, ERα and ERβ were detected by qRT-PCR (quantitative real-time polymerase chain reaction) in the ovariectomized and control groups. Compared with the control group, both mouse weight and transplanted tumour volume increased rapidly in the ovariectomized group, and the transplanted tumour weight was significantly heavier in the ovariectomized group (1.83±0.40 and 3.13±0.43, P<0.05). E2 and T serum levels decreased exponentially in the ovariectomized group, while the E2/T ratio increased compared with the control group (E2: 55.88±11.45 and

GLIS3 is indispensable for TSH/TSHR-dependent thyroid hormone biosynthesis and follicular cell proliferation

PubMed Central

Kang, Hong Soon; Kumar, Dhirendra; Liao, Grace; Lichti-Kaiser, Kristin; Gerrish, Kevin; Liao, Xiao-Hui; Refetoff, Samuel; Jothi, Raja; Jetten, Anton M.

2017-01-01

Deficiency in Krüppel-like zinc finger transcription factor GLI-similar 3 (GLIS3) in humans is associated with the development of congenital hypothyroidism. However, the functions of GLIS3 in the thyroid gland and the mechanism by which GLIS3 dysfunction causes hypothyroidism are unknown. In the current study, we demonstrate that GLIS3 acts downstream of thyroid-stimulating hormone (TSH) and TSH receptor (TSHR) and is indispensable for TSH/TSHR-mediated proliferation of thyroid follicular cells and biosynthesis of thyroid hormone. Using ChIP-Seq and promoter analysis, we demonstrate that GLIS3 is critical for the transcriptional activation of several genes required for thyroid hormone biosynthesis, including the iodide transporters Nis and Pds, both of which showed enhanced GLIS3 binding at their promoters. The repression of cell proliferation of GLIS3-deficient thyroid follicular cells was due to the inhibition of TSH-mediated activation of the mTOR complex 1/ribosomal protein S6 (mTORC1/RPS6) pathway as well as the reduced expression of several cell division–related genes regulated directly by GLIS3. Consequently, GLIS3 deficiency in a murine model prevented the development of goiter as well as the induction of inflammatory and fibrotic genes during chronic elevation of circulating TSH. Our study identifies GLIS3 as a key regulator of TSH/TSHR-mediated thyroid hormone biosynthesis and proliferation of thyroid follicular cells and uncovers a mechanism by which GLIS3 deficiency causes neonatal hypothyroidism and prevents goiter development. PMID:29083325

Plant hormone signaling lightens up: integrators of light and hormones.

PubMed

Lau, On Sun; Deng, Xing Wang

2010-10-01

Light is an important environmental signal that regulates diverse growth and developmental processes in plants. In these light-regulated processes, multiple hormonal pathways are often modulated by light to mediate the developmental changes. Conversely, hormone levels in plants also serve as endogenous cues in influencing light responsiveness. Although interactions between light and hormone signaling pathways have long been observed, recent studies have advanced our understanding by identifying signaling integrators that connect the pathways. These integrators, namely PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), PIF4, PIF3-LIKE 5 (PIL5)/PIF1 and LONG HYPOCOTYL 5 (HY5), are key light signaling components and they link light signals to the signaling of phytohormones, such as gibberellin (GA), abscisic acid (ABA), auxin and cytokinin, in regulating seedling photomorphogenesis and seed germination. This review focuses on these integrators in illustrating how light and hormone interact. Copyright © 2010 Elsevier Ltd. All rights reserved.

Early changes in plasma glucagon and growth hormone response to oral glucose in experimental hyperthyroidism.

PubMed

Tosi, F; Moghetti, P; Castello, R; Negri, C; Bonora, E; Muggeo, M

1996-08-01

The mechanisms underlying deterioration of glucose tolerance associated with hyperthyroidism are not completely understood. Increases in glucagon and growth hormone (GH) secretion have been previously found in hyperthyroid subjects, and could play a crucial role in this phenomenon. However, studies have not yet established the time sequence of changes in plasma glucose on the one hand and glucagon and GH on the other. To assess the early effects of thyroid hormone excess on glucose tolerance and plasma concentrations of the main glucoregulatory hormones, 12 nondiabetic euthyroid subjects underwent an oral glucose tolerance test (OGTT) before and after triiodothyronine ([T3] 120 micrograms/d) was administered for 10 days. Plasma levels of glucose, insulin, glucagon, and GH were determined at fasting and after the glucose load. T3 administration caused a marked increase in serum T3 (8.8 +/- 0.6 v 2.0 +/- 0.1 nmol/L), with clinical and biochemical signs of thyrotoxicosis. During the treatment, plasma glucose significantly increased both at fasting and after the glucose load (basal, 5.3 +/- 0.1 v 4.9 +/- 0.2 mmol/L, P < .05; area under the curve [AUC] for OGTT, 7.7 +/- 0.3 v 6.7 +/- 0.4 mmol/L min, P < .01) without any change in plasma insulin levels. After T3 administration, plasma glucagon levels were lower than at baseline (basal, 92 +/- 7 v 148 +/- 35 ng/L; AUC, 74 +/- 6 v 98 +/- 16 ng/L.min, P < .05), showing an appropriate reduction by the increased glucose levels. Conversely, plasma GH showed impaired suppression by hyperglycemia (AUC, 1.2 +/- 0.3 v 0.7 +/- 0.2 microgram/L.min, P < .05). In conclusion, thyroid hormone excess rapidly impairs glucose tolerance. Altered secretion of GH is an early event in thyrotoxicosis accompanying the onset of hyperglycemia, whereas plasma glucagon is appropriately suppressed by the increased plasma glucose levels. Thus, GH but not glucagon may contribute to the early hyperglycemic effect of thyrotoxicosis.

Effects of thyroid hormone on fast- and slow-twitch skeletal muscles in young and old rats.

PubMed Central

Larsson, L; Li, X; Teresi, A; Salviati, G

1994-01-01

1. The effects of 4 weeks of thyroid hormone treatment on contractile, enzyme-histochemical and morphometric properties and on the myosin isoform composition were compared in the slow-twitch soleus and the fast-twitch extensor digitorum longus (EDL) muscle in young (3-6 months) and old (20-24 months) male rats. 2. In the soleus of untreated controls, contraction and half-relaxation times of the isometric twitch increased by 19-32% with age. The change in contractile properties was paralleled by an age-related increase in the proportions of type I fibres and type I myosin heavy chain (MHC) and slow myosin light chain (MLC) isoforms. 3. In the EDL of controls, contraction and half-relaxation times were significantly prolonged (21-38%) in the post-tetanus twitch in the old animals. No significant age-related changes were observed in enzyme-histochemical fibre-type proportions, although the number of fibres expressing both type IIA and IIB MHCs and of fibres expressing slow MLC isoforms was increased in the old animals. 4. Serum 3,5,3',5'-tetraiodothyronine (T4) levels were lower (34%) in the old animals, but the primary byproduct of T4, 3,5,3'-triiodothyronine (T3), did not differ between young and old animals. 5. The effects of 4 weeks of thyroid hormone treatment were highly muscle specific, and were more pronounced in soleus than in EDL, irrespective of animal age. In the soleus, this treatment shortened the contraction and half-relaxation times by 35-57% and decreased the number of type I fibres by 66-77% in both young and old animals. In EDL, thyroid hormone treatment significantly shortened the contraction time by 24%, but the change was restricted to the old animals. 6. In conclusion, the ability of skeletal muscle to respond to thyroid hormone treatment was not impaired in old age and the age-related changes in speed of contraction and enzyme-histochemical properties and myosin isoform compositions were diminished after thyroid hormone treatment in both the

Graves' disease: an analysis of thyroid hormone levels and hyperthyroid signs and symptoms.

PubMed

Trzepacz, P T; Klein, I; Roberts, M; Greenhouse, J; Levey, G S

1989-11-01

Assessment of disease severity for patients with hyperthyroidism involves clinical evaluation and laboratory testing. To determine if there is a correlation between symptoms and thyroid function test results, we prospectively studied hyperthyroid patients using a standardized symptom rating scale and serum thyroid function parameters. We examined 25 patients with untreated, newly diagnosed Graves' disease using the Hyperthyroid Symptom Scale (HSS) and serum levels of thyroxine (T4), triiodothyronine (T3) relative insulin area (RIA), and estimates of free thyroxine index (FTI). In addition, we compared thyroid hormone levels with standard measures of depression and anxiety in these patients. When regression analyses controlling for age were performed, none of these symptom ratings were associated with FTI or T3 RIA. The HSS was correlated with goiter size and anxiety ratings and was inversely correlated with age. The present study suggests that there is no relationship between the clinical assessment of disease severity and serum levels of thyroid hormone in untreated Graves' disease.

A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone.

PubMed

Dos Santos, Christine; Essioux, Laurent; Teinturier, Cécile; Tauber, Maïté; Goffin, Vincent; Bougnères, Pierre

2004-07-01

Growth hormone is used to increase height in short children who are not deficient in growth hormone, but its efficacy varies largely across individuals. The genetic factors responsible for this variation are entirely unknown. In two cohorts of short children treated with growth hormone, we found that an isoform of the growth hormone receptor gene that lacks exon 3 (d3-GHR) was associated with 1.7 to 2 times more growth acceleration induced by growth hormone than the full-length isoform (P < 0.0001). In transfection experiments, the transduction of growth hormone signaling through d3-GHR homo- or heterodimers was approximately 30% higher than through full-length GHR homodimers (P < 0.0001). One-half of Europeans are hetero- or homozygous with respect to the allele encoding the d3-GHR isoform, which is dominant over the full-length isoform. These observations suggest that the polymorphism in exon 3 of GHR is important in growth hormone pharmacogenetics.

Increased Oxidative Metabolism and Neurotransmitter Cycling in the Brain of Mice Lacking the Thyroid Hormone Transporter Slc16a2 (Mct8)

PubMed Central

Rodrigues, Tiago B.; Ceballos, Ainhoa; Grijota-Martínez, Carmen; Nuñez, Barbara; Refetoff, Samuel; Cerdán, Sebastian; Morte, Beatriz; Bernal, Juan

2013-01-01

Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3) transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-13C) glucose and brain extracts prepared and analyzed by 13C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood. PMID:24098341

Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter SLC16A2 (MCT8).

PubMed

Rodrigues, Tiago B; Ceballos, Ainhoa; Grijota-Martínez, Carmen; Nuñez, Barbara; Refetoff, Samuel; Cerdán, Sebastian; Morte, Beatriz; Bernal, Juan

2013-01-01

Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3) transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-(13)C) glucose and brain extracts prepared and analyzed by (13)C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.

Reconstruction of 7T-Like Images From 3T MRI

PubMed Central

Bahrami, Khosro; Shi, Feng; Zong, Xiaopeng; Shin, Hae Won; An, Hongyu

2016-01-01

In the recent MRI scanning, ultra-high-field (7T) MR imaging provides higher resolution and better tissue contrast compared to routine 3T MRI, which may help in more accurate and early brain diseases diagnosis. However, currently, 7T MRI scanners are more expensive and less available at clinical and research centers. These motivate us to propose a method for the reconstruction of images close to the quality of 7T MRI, called 7T-like images, from 3T MRI, to improve the quality in terms of resolution and contrast. By doing so, the post-processing tasks, such as tissue segmentation, can be done more accurately and brain tissues details can be seen with higher resolution and contrast. To do this, we have acquired a unique dataset which includes paired 3T and 7T images scanned from same subjects, and then propose a hierarchical reconstruction based on group sparsity in a novel multi-level Canonical Correlation Analysis (CCA) space, to improve the quality of 3T MR image to be 7T-like MRI. First, overlapping patches are extracted from the input 3T MR image. Then, by extracting the most similar patches from all the aligned 3T and 7T images in the training set, the paired 3T and 7T dictionaries are constructed for each patch. It is worth noting that, for the training, we use pairs of 3T and 7T MR images from each training subject. Then, we propose multi-level CCA to map the paired 3T and 7T patch sets to a common space to increase their correlations. In such space, each input 3T MRI patch is sparsely represented by the 3T dictionary and then the obtained sparse coefficients are used together with the corresponding 7T dictionary to reconstruct the 7T-like patch. Also, to have the structural consistency between adjacent patches, the group sparsity is employed. This reconstruction is performed with changing patch sizes in a hierarchical framework. Experiments have been done using 13 subjects with both 3T and 7T MR images. The results show that our method outperforms previous

Physiologically-Based Pharmacokinetic (PBPK) Model for the Thyroid Hormones in the Pregnant Rat and Fetus.

EPA Science Inventory

A developmental PBPK model is constructed to quantitatively describe the tissue economy of the thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), in the rat. The model is also used to link maternal (THs) to rat fetal tissues via placental transfer. THs are importan...