scholarly journals Thyroid Hormones Decrease Plasma 1α,25-Dihydroxyvitamin D Levels Through Transcriptional Repression of the Renal 25-Hydroxyvitamin D3 1α-Hydroxylase Gene (CYP27B1)

Endocrinology ◽  
2013 ◽  
Vol 154 (2) ◽  
pp. 609-622 ◽  
Author(s):  
Mina Kozai ◽  
Hironori Yamamoto ◽  
Mariko Ishiguro ◽  
Nagakatsu Harada ◽  
Masashi Masuda ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Gene Transcription ◽  
Transcriptional Repression ◽  
Transcriptional Activity ◽  
Plasma Concentrations ◽  
Mrna Levels ◽  
Dihydroxyvitamin D ◽  
Low Calcium Diet ◽  
Low Calcium

The primary determinant of circulating 1α,25-dihydroxyvitamin D (1,25[OH]2D) levels is the activity of 25-hydroxyvitamin D-1α-hydroxylase (cytochrome P450 27B1 [CYP27B1]) in the kidney. Hyperthyroid patients have been reported to have low levels of plasma 1,25(OH)2D. However, the detailed mechanism of thyroid hormone action on vitamin D metabolism is still poorly understood. The present study determined whether renal CYP27B1 gene expression was negatively regulated by thyroid hormones. T3-induced hyperthyroid mice showed marked decreases in plasma 1,25(OH)2D levels and in renal expression of CYP27B1 mRNA but no changes in plasma concentrations of calcium, PTH, or fibroblast growth factor-23. In addition, we observed that T3 administration significantly decreased plasma 1,25(OH)2D and renal CYP27B1 mRNA levels that were increased by low-calcium or low-phosphorus diets and induced hypocalcemia in mice fed a low-calcium diet. Promoter analysis revealed that T3 decreases the basal transcriptional activity of the CYP27B1 gene through thyroid hormone receptors (TRα and TRβ1) and the retinoid X receptor α (RXRα) in renal proximal tubular cells. Interestingly, we identified an everted repeat negative thyroid hormone response element (1α-nTRE) overlapping the sterol regulatory element (1α-SRE) and the TATA-box −50 to −20 base pairs from the human CYP27B1 gene transcription start site. Finally, we established that CYP27B1 gene transcription is positively regulated by SRE-binding proteins and that a T3-bound TRβ1/RXRα heterodimer inhibits SRE-binding protein-1c-induced transcriptional activity through the 1α-nTRE. These results suggest that transcriptional repression of the CYP27B1 gene by T3-bound TRs/RXRα, acting through the 1α-nTRE, results in decreased renal CYP27B1 expression and plasma 1,25(OH)2D levels.

scholarly journals Intestinal Resistance to 1,25 Dihydroxyvitamin D in Mice Heterozygous for the Vitamin D Receptor Knockout Allele

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1396-1402 ◽  
Author(s):  
Yurong Song ◽  
James C. Fleet
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Time Course ◽  
Transient Receptor Potential ◽  
Gene Knockout ◽  
Mrna Levels ◽  
Wild Type ◽  
Calcium Diet ◽  
Low Calcium Diet ◽  
Low Calcium

We tested the hypothesis that low vitamin D receptor (VDR) level causes intestinal vitamin D resistance and intestinal calcium (Ca) malabsorption. To do so, we examined vitamin D regulated duodenal Ca absorption and gene expression [transient receptor potential channel, vallinoid subfamily member 6 (TRPV6), 24-hydroxylase, calbindin D9k (CaBP) mRNA, and CaBP protein] in wild-type mice and mice with reduced tissue VDR levels [i.e. heterozygotes for the VDR gene knockout (HT)]. Induction of 24-hydroxylase mRNA levels by 1,25 dihydroxyvitamin D3 [1,25(OH)2 D3] injection was significantly reduced in the duodenum and kidney of HT mice in both time-course and dose-response experiments. TRPV6 and CaBP mRNA levels in duodenum were significantly induced after 1,25(OH)2 D3 injection, but there was no difference in response between wild-type and HT mice. Feeding a low-calcium diet for 1 wk increased plasma PTH, renal 1α-hydroxylase (CYP27B1) mRNA level, and plasma 1,25(OH)2 D3, and this response was greater in HT mice (by 88, 55, and 37% higher, respectively). In contrast, duodenal TRPV6 and CaBP mRNA were not higher in HT mice fed the low-calcium diet. However, the response of duodenal Ca absorption and CaBP protein to increasing 1,25(OH)2 D3 levels was blunted by 40% in HT mice. Our data show that low VDR levels lead to resistance of intestinal Ca absorption to 1,25(OH)2 D3, and this resistance may be due to a role for the VDR (and VDR level) in the translation of CaBP.

Thyroid hormone concentrations in the plasma of fed and fasted Brahman and Hereford steers

1994 ◽  
Vol 34 (4) ◽  
pp. 439
Author(s):  
JC O'Kelly ◽  
WG Spiers
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Plasma Concentrations ◽  
Free T4 ◽  
Rumen Metabolism ◽  
Body Tissues ◽  
Breed Differences ◽  
Feeding Regimes ◽  
Ad Libitum ◽  
Brahman Steers

Plasma concentration patterns of thyroxine (TJ, free T4 (FT4), triiodothyronine (T3), and free T3 (FT3) were determined in Brahman steers fed lucerne hay ad libitum and in Brahman and Hereford steers fed restricted intakes of lucerne hay at the rate of either 208 g/h before fasting for 72 h or 250 g/h before fasting for 96 h. In Brahmans fed ad libitum, the plasma concentrations of all thyroid hormone fractions were significantly (P<0.01) correlated with one another and with feed intake. Within breeds, the concentrations of thyroid hormones were higher (P<0.001) when animals were fed at 250 g k than at 208 g/h. During both hourly feeding regimes T4, FT4, T3, and FT3 concentrations were higher (P<0.001) in Brahmans than in Herefords. Fasting after both hourly feeding regimes lowered (P<0.001) the concentrations of T4 about 53% in Brahmans and 30% in Herefords, while FT4, T3, and FT3 were lowered about 68% in Brahmans and 50% in Herefords. Consequently, thyroid hormone concentrations were significantly lower in Brahmans than in Herefords after 72 h fasting but did not differ significantly between breeds after 96 h fasting. The present results, together with those of our previous work showing breed differences in rumen metabolism, support the concept that, in Hereford and Brahman steers fed the same amount of hay in a thermoneutral environment, breed differences in plasma concentrations of thyroid hormones originate from quantitative differences in the supply of nutrients from the rumen to body tissues.

scholarly journals Ontogeny of pituitary thyrotrophs and regulation by endogenous thyroid hormone feedback in the chick embryo

2005 ◽  
Vol 184 (2) ◽  
pp. 407-416 ◽  
Author(s):  
Michael Muchow ◽  
Ioannis Bossis ◽  
Tom E Porter
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Anterior Pituitary ◽  
Feedback Regulation ◽  
Thyroid Stimulating Hormone ◽  
Mrna Levels ◽  
Hormone Production ◽  
Negative Feedback Regulation ◽  
Cephalic Lobe ◽  
Whole Mount

Increased thyroid hormone production is essential for hatching of the chick and for the increased metabolism necessary for posthatch endothermic life. However, little is known about the ontogeny and distribution of pituitary thyrotrophs during this period or whether pituitary thyroid-stimulating hormone (TSH) production is regulated by endogenous thyroid hormones during chick embryonic development. This study assessed the abundance and location of pituitary thyrotrophs and the regulation of TSHβ peptide and mRNA levels by endogenous thyroid hormones prior to hatching. TSHβ-containing cells were first detected on embryonic day (e) 11, and the thyrotroph population increased to maximum levels on e17 and e19 and then decreased prior to hatching (d1). Thyrotroph distribution within the cephalic lobe of the anterior pituitary was determined on e19 by whole-mount immunocytochemistry for TSHβ peptide and by whole-mount in situ hybridization for TSHβ mRNA. Thyrotroph distribution within the cephalic lobe was heterogeneous among embryos, but most commonly extended from the ventral medial region to the dorsal lateral regions, along the boundary of the cephalic and caudal lobes. Inhibition of endogenous thyroid hormone production with methi-mazole (MMI) decreased plasma thyroxine (T4) levels and increased pituitary TSHβ mRNA levels on e19 and d1. However, control pituitaries contained significantly more TSHβ peptide than MMI-treated pituitaries on e17 and e19, suggesting higher TSH secretion into the blood in MMI-treated groups. We conclude that thyrotroph abundance and TSH production increase prior to hatching, that thyrotrophs are localized heterogenenously within the cephalic lobe of the anterior pituitary at that time, and that TSH gene expression and secretion are under negative feedback regulation from thyroid hormones during this critical period of development.

scholarly journals Athyroid Pax8−/− Mice Cannot Be Rescued by the Inactivation of Thyroid Hormone Receptor α1

Endocrinology ◽  
2005 ◽  
Vol 146 (7) ◽  
pp. 3179-3184 ◽  
Author(s):  
Jens Mittag ◽  
Sönke Friedrichsen ◽  
Heike Heuer ◽  
Silke Polsfuss ◽  
Theo J. Visser ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Postnatal Life ◽  
Mrna Levels ◽  
Negative Effects ◽  
Double Knockout ◽  
Short Life Span ◽  
Knockout Animals

Abstract The Pax8−/− mouse provides an ideal animal model to study the consequences of congenital hypothyroidism, because its only known defect is the absence of thyroid follicular cells. Pax8−/− mice are, therefore, completely athyroid in postnatal life and die around weaning unless they are substituted with thyroid hormones. As reported recently, Pax8−/− mice can also be rescued and survive to adulthood by the additional elimination of the entire thyroid hormone receptor α (TRα) gene, yielding Pax8−/−TRαo/o double-knockout animals. This observation has led to the hypothesis that unliganded TRα1 might be responsible for the lethal phenotype observed in Pax8−/− animals. In this study we report the generation of Pax8−/−TRα1−/− double-knockout mice that still express the non-T3-binding TR isoforms α2 and Δα2. These animals closely resemble the phenotype of Pax8−/− mice, including growth retardation and a completely distorted appearance of the pituitary with thyrotroph hyperplasia and hypertrophy, extremely high TSH mRNA levels, reduced GH mRNA expression, and the almost complete absence of lactotrophs. Like Pax8−/− mice, Pax8−/−TRα1−/− compound mutants die around weaning unless they are substituted with thyroid hormones. These findings do not support the previous interpretation that the short life span of Pax8−/− mice is due to the negative effects of the TRα1 aporeceptor, but, rather, suggest a more complex mechanism involving TRα2 and an unliganded TR isoform.

scholarly journals Lack of Insulin-Like Growth Factor I Exaggerates the Effect of Calcium Deficiency on Bone Accretion in Mice

Endocrinology ◽  
2003 ◽  
Vol 144 (11) ◽  
pp. 4682-4689 ◽  
Author(s):  
Yuji Kasukawa ◽  
David J. Baylink ◽  
Jon E. Wergedal ◽  
Yousef Amaar ◽  
Apurva K. Srivastava ◽  
...  
Keyword(s):  
Calcium Deficiency ◽  
Growth Phases ◽  
Active Growth ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Calcium Diet ◽  
Low Calcium Diet ◽  
Low Calcium ◽  
Igf I ◽  
Normal Calcium

Abstract Recent studies provide evidence that the GH/IGF-I axis plays a critical role in the regulation of bone accretion that occurs during puberty and that the peak bone mineral density (BMD) is dependent on the amount of dietary calcium intake during the active growth phases. To evaluate whether IGF-I deficiency exaggerates the effect of calcium deficiency on bone accretion during active growth phases, IGF-I knockout (KO) and wild-type (WT) mice were fed with low calcium (0.01%) or normal calcium (0.6%) for 2 wk during the pubertal growth phase and were labeled with tetracycline. The low calcium diet caused significant decreases in endosteal bone formation parameters and a much greater increase in the resorbing surface of both the endosteum and periosteum of the tibia of IGF-I KO mice compared with WT mice. Accordingly, femur BMD measured by dual energy x-ray absorptiometry or peripheral quantitative computed tomography increased significantly in IGF-I WT mice fed the low calcium diet, but not in IGF-I KO mice. IGF-I-deficient mice fed the normal calcium diet showed elevated PTH levels, decreased serum 1,25-dihydroxyvitamin D and serum calcium levels at baseline. Serum calcium changes due to calcium deficiency were greater in IGF-I KO mice compared with WT mice. PTH levels were 7-fold higher in IGF-I KO mice fed normal calcium compared with WT mice, which was further elevated in mice fed the low calcium diet. Treatment of IGF-I-deficient lit/lit mice with GH decreased the serum PTH level by 70% (P &lt; 0.01). Based on these and past findings, we conclude that: 1) IGF-I deficiency exaggerates the negative effects of calcium deficiency on bone accretion; and 2) IGF-I deficiency may lead to 1,25-dihydroxyvitamin D deficiency and elevated PTH levels even under normal calcium diet.

Manipulation of thyroid hormones in ruminants - a tool to understand their physiological role and identify their potential for increasing production efficiency

2002 ◽  
Vol 53 (3) ◽  
pp. 259 ◽  
Author(s):  
D. Villar ◽  
S. M. Rhind ◽  
J. R. Arthur ◽  
P. J. Goddard
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Production Efficiency ◽  
Hormone Replacement ◽  
Animal Health ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
Physiological Role ◽  
Antithyroid Drugs ◽  
Few Data

Manipulations of thyroid hormone secretion and function can be used to cure thyroidal deficiencies or overactivity and as a tool to investigate their physiological roles and identify potential protocols for enhancing animal performance. An essential approach to the investigation of thyroid hormone action involves the induction of hypothyroidal states. Methods of inducing hypothyroidal states in ruminants include thyroidectomy and treatment with thionamides. There are few data concerning the induction of an optimal degree of hypothyroidism for the study of thyroid function in ruminants, unlike the situation in rodents. The effects of hypothyroidism on the physiology of ruminants, and the relative merits of thyroidectomy or of treatment with thionamides to manipulate thyroid hormone profiles in them, are reviewed and discussed. Thyroidectomy in ruminants induces an acute, irreversible, hypothyroidal state. It also has indirect, predominantly adverse, effects on many physiological processes and impairs health. Thus, thyroidectomised (THX) animals cannot be sustained for long-term studies without thyroid hormone replacement. Antithyroid drugs of the thionamide class, on the other hand, have been used with success to induce varying degrees of hypothyroidism, predominantly less severe than those induced by thyroidectomy. The changes induced by drugs are reversible upon withdrawal of treatment. However, treatment may require daily administration of the drug for several weeks before stable plasma concentrations of thyroid hormone are achieved. Furthermore, at high doses, these drugs can have toxic side effects. It is concluded that the treatment regime of choice will depend on the objectives of the individual study. Knowledge of the activities of thyroid hormone metabolising, deiodinase enzymes in the target tissues is also required if the actions of some of these drugs, their physiological roles in modulation of the thyroid hormones, and, crucially, their potential effects on animal health and production are to be properly understood and exploited.

scholarly journals A Defect in Nucleosome Remodeling Prevents IL-12(p35) Gene Transcription in Neonatal Dendritic Cells

2004 ◽  
Vol 199 (7) ◽  
pp. 1011-1016 ◽  
Author(s):  
Stanislas Goriely ◽  
Carine Van Lint ◽  
Réza Dadkhah ◽  
Myriam Libin ◽  
Dominique De Wit ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Gene Transcription ◽  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Gene Activation ◽  
Mrna Levels ◽  
Recombinant Interferon ◽  
Nucleosome Remodeling ◽  
P35 Gene

To gain insight into the inability of newborns to mount efficient Th1 responses, we analyzed the molecular basis of defective IL-12(p35) expression in human neonatal monocyte-derived dendritic cells (DCs). Determination of IL-12(p35) pre-mRNA levels by real-time RT-PCR revealed that transcriptional activation of the gene in lipopolysaccharide-stimulated neonatal DCs was strongly impaired compared with adult DCs. We next showed that p50/p65 and p65/p65 dimers interact with kB#1 site, a critical cis-acting element of the IL-12(p35) promoter. We found that LPS-induced p65 activation was similar in adult and newborn DCs. Likewise, in vitro binding activity to the Sp1#1 site, previously shown to be critical for IL-12(p35) gene activation, did not differ in adults and newborns. Since the accessibility to this Sp1#1 site was found to depend on nucleosome remodeling, we used a chromatin accessibility assay to compare remodeling of the relevant nucleosome (nuc-2) in adult and neonatal DCs. We observed that nuc-2 remodeling in neonatal DCs was profoundly impaired in response to lipopolysaccharide. Both nuc-2 remodeling and IL-12(p35) gene transcription were restored upon addition of recombinant interferon-γ. We conclude that IL-12(p35) transcriptional repression in neonatal DCs takes place at the chromatin level.

scholarly journals Applicability of thyroxine measurements and ultrasound imaging in evaluations of thyroid function in turtles

2019 ◽  
Vol 63 (2) ◽  
pp. 267-273
Author(s):  
Joanna Pajdak-Czaus ◽  
Elżbieta Terech-Majewska ◽  
Dagmara Będzłowicz ◽  
Martyn Mączyński ◽  
Wioletta Krystkiewicz ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Thyroid Hormones ◽  
Thyroid Function ◽  
Ultrasound Imaging ◽  
Ultrasound Examination ◽  
Plasma Concentrations ◽  
Physiological Homeostasis ◽  
Low Levels ◽  
And Function

AbstractIntroduction: The thyroid and parathyroid glands play a major role in maintaining physiological homeostasis in all vertebrates. Reptiles have plasma concentrations of thyroid hormones far lower than mammals. Low levels of these hormones in reptiles impede thyroid hormone detection with assays designed for the higher levels of mammals. The aim of this study was to explore teaming this with ultrasound imaging of the thyroid to appraise glandular function. Material and Methods: Thyroid function of four pond sliders was evaluated based on the results of T4 analyses and ultrasound. Results: The concentrations of T4 varied considerably between the examined animals from <9 nmol/L to >167.3 nmol/L. Ultrasound examination revealed uniform echogenicity and a smooth outline of the thyroid gland in all animals. Conclusion: Monitoring of thyroid function based on T4 and electrolyte concentrations is helpful in assessing the health and living conditions of reptiles, which is important in veterinary practice but problematic. Ultrasound examinations are useful in diagnosing changes in gland structure, such as tumours and goitres, and a combination of both methods supports comprehensive assessments of the anatomy and function of the thyroid gland.

Long-lasting effects of Triac and thyroxine on the control of thyrotropin and hepatic deiodinase type I

1995 ◽  
Vol 132 (6) ◽  
pp. 751-758 ◽  
Author(s):  
Cristiana E Juge-Aubry ◽  
Odette Morin ◽  
Agnés T Pernin ◽  
Hong Liang ◽  
Jacques Philippe ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Gradual Increase ◽  
Biological Effects ◽  
Type I ◽  
Mrna Levels ◽  
Spot 14 ◽  
Stopping Treatment ◽  
Serum Tsh ◽  
Tsh Levels

Juge-Aubry CE, Morin 0, Pernin AT, Liang H, Phillipe J, Burger AG. Long-lasting effects of Triac and thyroxine on the control of thyrotropin and hepatic deiodinase type I. Eur J Endocrinol 1995;132:751–8. The purpose of this study was to investigate the relation between the serum levels of thyroid hormones and their biological effects. For this purpose, hypothyroid rats were studied after stopping treatment with a long-acting thyroid hormone, thyroxine (T4) and a short-acting one, triiodothyroacetic acid (Triac). Based on preliminary experiments with different doses of T4 and Triac, hypothyroid rats (N= 84) received over 6 days' injections of lOnmol Triac or 2 nmol T4/100 g body wt per day. Biological effects of Triac and T4 were measured in the pituitary, liver and kidney up to 8 days after stopping treatment. With Triac, serum thyrotropin (TSH) levels were inhibited completely 6 h after injection, yet after 24 h they were 4.9 ± 1.8 μ/l (hypothyroid 14.5 ± 0.8 μg/l). The rapid changes in serum TSH levels were followed by a more gradual increase in serum TSH levels were followed by a more gradual increase in serum TSH, which was similar to that after T4 injection. Even 8 days after Triac treatment, serum TSH levels did not reach the hypothyroid control levels. Changes in β-TSH mRNA levels also showed a prolonged inhibition after both treatments and a slow return to hypothyroid values, which was not complete 8 days after stopping treatment. A second parameter was hepatic 5′-deiodinase type I (5′D-I), The 6-day treatment with Triac had a markedly stronger effect on 5′D-I enzyme activity and mRNA levels than treatment with T4. Again, the effect disappeared slowly because hepatic activity was still above control levels 8 days after treatment. The mRNA levels of spot 14 also were higher with Triac. However, 4 days after stopping treatment with both hormones, mRNA levels had returned to hypothyroid values. These data suggest that at the pituitary level one can distinguish between rapid and slower effects. For 5′D-I activity, however, the effects are longlasting and there is no apparent difference in the duration of the effects between Triac or T4. They last much longer than the injected hormone. Our results show that even for parameters closely controlled by thyroid hormones, the expression and duration of thyroid hormone effects vary markedly, not only from organ to organ TSH/5′D-I but also within the same organ, depending on the parameters (5′D-I/ spot 14). Cristiana E Juge-Aubry, Thyroid Unit, Hôpital Cantonal Universitaire, 1211 Geneva 14, Switzerland

Thyroid hormone-induced stimulation of the sarcoplasmic reticulum Ca2+ ATPase gene is inhibited by LIF and IL-6

2000 ◽  
Vol 278 (4) ◽  
pp. E738-E743 ◽  
Author(s):  
Bernd Gloss ◽  
Sonia Villegas ◽  
Francisco J. Villarreal ◽  
Anselmo Moriscot ◽  
Wolfgang H. Dillmann
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Myocytes ◽  
Transcriptional Activity ◽  
Neonatal Rat ◽  
Mrna Levels ◽  
Cytokine Inhibition ◽  
Atpase Gene ◽  
Promoter Construct

We investigated the effects of the leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) on 3,3′, 5-triiodo-l-thyronine, or thyroid hormone (T3)-stimulated sarcoplasmic reticulum Ca2+ATPase (SERCA2) gene expression on cultured neonatal rat cardiac myocytes. A reduction of T3 induced increases in SERCA2 mRNA levels after co-treatment with LIF or IL-6. To investigate for the molecular mechanism(s) responsible for the blunted gene expression, a 3.2-kb SERCA2 promoter construct containing a reporter gene was transfected into cardiac myocytes. T3 treatment stimulated transcriptional activity twofold, whereas co-treatment with T3 and either of the cytokines caused an inhibition of T3-induced SERCA2 transcriptional activity. A T3-responsive 0.6-kb SERCA2 construct also showed a similar inhibition by cytokines. Cytokine inhibition of SERCA2 transcriptional activity was also evident when a 0.6-kb SERCA2 mutant, T3-unresponsive promoter construct was used. Treatment with T3 and cytokines showed a significant decrease in transcription when a reporter construct was used that was comprised of direct repeats of SERCA2 thyroid response element I. These data provide evidence for cytokine-mediated inhibitory effects on the SERCA2 promoter that may be mediated by interfering with T3action.

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