Consequences of thyroid hormone deficiency induced by the specific ablation of thyroid follicle cells in adult transgenic mice

1994 ◽  
Vol 143 (1) ◽  
pp. 107-120 ◽  
Author(s):  
H Wallace ◽  
K McLaren ◽  
R Al-Shawi ◽  
J O Bishop
Keyword(s):  
Body Weight ◽  
Thyroid Hormone ◽  
Transgenic Mice ◽  
Follicle Cells ◽  
Hormone Deficiency ◽  
Mrna Levels ◽  
Thyroid Follicle ◽  
Receptor Mrna ◽  
The Many ◽  
Tsh Levels

Abstract The herpes simplex type 1 virus thymidine kinase (HSV1-TK) reporter gene was coupled to a bovine thyroglobulin promoter (TG-tk construct). Within the thyroid glands of transgenic mice expression was confined to thyroid follicle cells. Infusion of Ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl]guanine) to 8 to 12 week transgenic females led to the complete loss of thyroid HSV1-TK activity (at 3 to 4 days) and thyroid follicles (between 7 and 14 days). During the first 5 days of treatment a single reciprocal oscillation in circulating thyroxine (T4) and TSH levels occurred. By 14 days the circulating triiodothyronine (T3) and T4 levels of all treated animals were below the detection limits of the assays, while TSH levels were elevated ten-fold and continued to increase thereafter. During 14 days of treatment the thyroids regressed, protein content fell by 80–90% and the C cells, normally dispersed within the central region of each gland, came together in aggregates. Pituitary GH levels in females rose and fell back to normal within 14 days and between 14 and 28 days fell to a level comparable with that of GH-deficient lit/lit mice. The levels of hepatic GH receptor mRNA and the predominant 6·6 kb T3 receptor mRNA were unaffected by thyrocyte ablation. Thyrocyte ablation had no effect on the level of prolactin (Prl) receptor mRNA in females, but increased Prl receptor mRNA levels in males and eliminated group 1 major urinary protein (MUP) mRNA in females. T4 replacement reversed the effects of thyrocyte ablation on MUP mRNA in females and on Prl receptor mRNA in males. Despite the many physiological changes induced by thyrocyte ablation, ablated mice have been maintained for up to 1 year without thyroid hormone supplementation. T4-deficient females were normally fertile and carried pups to term. Although transgenic males expressed HSV1-TK ectopically in spermatids and spermatozoa at levels similar to thyrocyte levels, a rate of Ganciclovir infusion which successfully ablated the thyrocytes did not affect the testis. As an alternative to infusion by minipump, thyrocyte ablation could be achieved by 6 twice-daily injections of Ganciclovir, at a level of 112 μg Ganciclovir/g body weight per day, and fetuses in utero could be thyrocyte ablated by administering 50 or 15 μg/g body weight per day to pregnant females between days 14 and 18 of gestation. These data demonstrate the potential value of transgenic thyrocyte ablation in the study of the effects of thyroid hormone deprivation. Journal of Endocrinology (1994) 143, 107–120

Thyroid hormone is required for the phenotype transitions induced by the pharmacological inhibition of calcineurin in adult soleus muscle of rats

2008 ◽  
Vol 294 (1) ◽  
pp. E69-E77 ◽  
Author(s):  
Nathalie Koulmann ◽  
Lahoucine Bahi ◽  
Florence Ribera ◽  
Hervé Sanchez ◽  
Bernard Serrurier ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Soleus Muscle ◽  
Hormone Deficiency ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Thyroid State ◽  
Novel Approach ◽  
A Subunit ◽  
Calcineurin Inhibition

The present experiment was designed to examine the effects of hypothyroidism and calcineurin inhibition induced by cyclosporin A (CsA) administration on both contractile and metabolic soleus muscle phenotypes, with a novel approach to the signaling pathway controlling mitochondrial biogenesis. Twenty-eight rats were randomly assigned to four groups, normothyroid, hypothyroid, and orally treated with either CsA (25 mg/kg, N-CsA and H-CsA) or vehicle (N-Vh and H-Vh), for 3 wk. Muscle phenotype was estimated by the MHC profile and activities of oxidative and glycolytic enzymes. We measured mRNA levels of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), the major regulator of mitochondrial content. We also studied the expression of the catalytic A-subunit of calcineurin (CnA) both at protein and transcript levels and mRNA levels of modulatory calcineurin inhibitor proteins (MCIP)-1 and -2, which are differentially regulated by calcineurin activity and thyroid hormone, respectively. CsA-administration induced a slow-to-fast MHC transition limited to the type IIA isoform, which is associated with increased oxidative capacities. Hypothyroidism strongly decreased both the expression of fast MHC isoforms and oxidative capacities. Effects of CsA administration on muscle phenotype were blocked in conditions of thyroid hormone deficiency. Changes in the oxidative profile were strongly related to PGC-1α changes and associated with phosphorylation of p38 MAPK. Calcineurin and MCIPs mRNA levels were decreased by both hypothyroidism and CsA without additive effects. Taken together, these results suggest that adult muscle phenotype is primarily under the control of thyroid state. Physiological levels of thyroid hormone are required for the effects of calcineurin inhibition on slow oxidative muscle phenotype.

Chronic mild stress induces widespread decreases in thyroid hormone α1 receptor mRNA levels in brain—Reversal by imipramine

2009 ◽  
Vol 34 (2) ◽  
pp. 281-286 ◽  
Author(s):  
Edward J. Stein ◽  
Nylson G. da Silveira Filho ◽  
Danilo C. Machado ◽  
Débora C. Hipólide ◽  
Karen Barlow ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Mrna Levels ◽  
Receptor Mrna

Differential regulation of thyrotropin-releasing hormone receptor mRNA levels by thyroid hormone in vivo and in vitro (GH3 cells)

1992 ◽  
Vol 184 (1) ◽  
pp. 367-372 ◽  
Author(s):  
Masanobu Yamada ◽  
Tuyoshi Monden ◽  
Teturou Satoh ◽  
Masahiko Iizuka ◽  
Masami Murakami ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Differential Regulation ◽  
Thyrotropin Releasing Hormone ◽  
Gh3 Cells ◽  
Mrna Levels ◽  
Releasing Hormone ◽  
Receptor Mrna

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

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

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

Specific Ablation of Thyroid Follicle Cells in Adult Transgenic Mice*

Endocrinology ◽  
1991 ◽  
Vol 129 (6) ◽  
pp. 3217-3226 ◽  
Author(s):  
HELEN WALLACE ◽  
CATHERINE LEDENT ◽  
GILBERT VASSART ◽  
JOHN O. BISHOP ◽  
RAYA AL-SHAWI
Keyword(s):  
Transgenic Mice ◽  
Follicle Cells ◽  
Thyroid Follicle

scholarly journals The immune status of preschool children with diffuse enlargement of the thyroid under ecologically adverse conditions

1995 ◽  
Vol 41 (3) ◽  
pp. 23-25
Author(s):  
L. N. Ulanova ◽  
А. М. Zemskov ◽  
V. I. Knyazev
Keyword(s):  
Preschool Children ◽  
Thyroid Hormone ◽  
Functional Activity ◽  
Immune Status ◽  
Close Correlation ◽  
Hormone Deficiency ◽  
Equal Frequency ◽  
Thyroid Activity ◽  
Adverse Conditions ◽  
Tsh Levels

A total of 434 children aged 4 to 7 living under ecologically adverse conditions were examined. Diffuse enlargement of the thyroid was detected in 35% of children (I degree in 62%, II degree in 38%), with equal frequency in boys and girls. This research was aimed at assessing the immune status of children with enlargement of the thyroid of different degree and at estimation of the functional activity of the thyroid by clinical and laboratory signs (T3, T4, TSH, whose concentrations were measured by standard radioimmunoassay and enzyme immunoassay). Preschool children with diffuse enlargement of the thyroid presented with immunocyte depression in the blood, which was evidently a result of thyroid hormone deficiency at the level of cellular metabolism, because the function of tire enlarged thyroid was frequently reduced, that is, compensated or decompensated hypothyroid state was present. Immunologic disturbances depended on the degree of diffuse enlargement of the gland and on the presence and degree of thyroid activity reduction. A close correlation between blood T4 and TSH levels and immunity status parameters was detected.

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

scholarly journals Pituitary Hormone Gene Expression and Secretion in Human Growth Hormone-Releasing Hormone Transgenic Mice: Focus on Lactotroph Function1

Endocrinology ◽  
2000 ◽  
Vol 141 (1) ◽  
pp. 81-90 ◽  
Author(s):  
Joseph P. Moore ◽  
Aihua Cai ◽  
Mary Ellen Hostettler ◽  
Lydia A. Arbogast ◽  
James L. Voogt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tyrosine Hydroxylase ◽  
Transgenic Mice ◽  
Transgenic Mouse ◽  
Anterior Pituitary ◽  
Receptor Gene ◽  
D2 Receptor ◽  
Mrna Levels ◽  
Receptor Mrna ◽  
Receptor Gene Expression

Abstract The human GH-releasing hormone (hGHRH) transgenic mouse has a hyperplastic anterior pituitary gland that eventually develops into an adenoma. We showed previously that the number of lactotrophs in the male hGHRH transgenic mouse is increased 2-fold, yet there is no concomitant increase in plasma levels of PRL. To further elucidate underlying changes in lactotroph function in the hGHRH transgenic mouse, the objectives of this study were to 1) examine the relative differences in PRL gene expression in transgenic mice and their siblings, 2) quantify PRL secretion at the level of the individual cell, 3) determine whether tyrosine hydroxylase gene expression and/or activity are altered in the hypothalamus of transgenic mice, and 4) assess dopamine receptor gene expression and functional sensitivity in lactotrophs of transgenic mice. Total PRL messenger RNA (mRNA) levels were increased nearly 5-fold in the hGHRH transgenic mouse, whereas the concentrations of PRL mRNA (PRL mRNA per μg total RNA) were unchanged. In contrast, total PRL contents were unchanged, whereas the concentrations of PRL (micrograms of PRL per mg total protein) were decreased 3-fold. Hypothalamic tyrosine hydroxylase steady state mRNA levels were not altered in the hGHRH transgenic mice, but hypothalamic tyrosine hydroxylase activity was increased 2-fold in transgenic mice. Dopamine D2 receptor mRNA concentrations in the anterior pituitary were increased 2.5-fold in hGHRH transgenic mice, and total pituitary D2 receptor mRNA levels were increased nearly 10-fold. Furthermore, the basal secretory capacity of lactotrophs from transgenic mice was increased significantly at the level of the single cell, and dopamine inhibited the secretion of PRL to a greater extent in hGHRH transgenic mice. Thus, although the total number of lactotrophs is increased 2-fold in hGHRH transgenic mice, the present data are consistent with the hypothesis that increased hypothalamic dopamine synthesis and release coupled with an increase in D2 dopamine receptor gene expression and functional sensitivity in the pituitary result in normal plasma levels of PRL.

scholarly journals A GH receptor antisense oligonucleotide inhibits hepatic GH receptor expression, IGF-I production and body weight gain in normal mice

2006 ◽  
Vol 189 (1) ◽  
pp. 147-154 ◽  
Author(s):  
G Tachas ◽  
S Lofthouse ◽  
C J Wraight ◽  
B F Baker ◽  
N B Sioufi ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Antisense Oligonucleotide ◽  
Body Weight Gain ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Receptor Mrna ◽  
Gh Receptor ◽  
Igf I

Diabetic retinopathy and acromegaly are diseases associated with excess action of GH and its effector IGF-I, and there is a need for improved therapies. We have designed an optimised 2′-O-(2-methoxyethyl)-modified phosphorothioate oligodeoxynucleotide, ATL 227446, and demonstrated its ability to suppress GH receptor mRNA in vitro. Subcutaneous injections of ATL 227446 reduced GH receptor mRNA levels, GH binding activity and serum IGF-I levels in mice after seven days of dosing. The reduction in serum IGF-I could be sustained for over ten weeks of dosing at therapeutically relevant levels, during which there was also a significant decrease in body weight gain in antisense-treated mice relative to saline and mismatch control-treated mice. The findings indicate that administration of an antisense oligonucleotide to the GH receptor may be applicable to human diseases in which suppression of GH action provides therapeutic benefit.

The ultracytochemical localization of cytidine-5'-monophosphatase in normal human thyroid follicle cells.

1980 ◽  
Vol 28 (5) ◽  
pp. 413-418
Author(s):  
W A Shannon ◽  
S I Roth
Keyword(s):  
Alkaline Phosphatase ◽  
Thyroid Hormone ◽  
Golgi Apparatus ◽  
Follicle Cells ◽  
Human Thyroid ◽  
Thyroid Follicle ◽  
Manganese Ion ◽  
The Face ◽  
Normal Human ◽  
Relationship Of

The properties and distribution of an enzyme specifically hydrolyzing cytidine-5'-monophosphate and the possible relationship of the enzyme to the synthesis and secretion of thyroid hormone in man were investigated using cytochemical methods. Activity due to cytidine-5'-monophosphatase was separated from that due to acid or alkaline phosphatase, both of which are also capable of hydrolyzing cytidine-5'-monophosphate. This distinction was established on the basis of manganese ion stimulation and differences in localization, levels of activity, and pH optimums. The localization of the enzyme along the face of Golgi apparatus involved in the formation of thyroglobulin suggests an association of the enzyme with the glycosylation of thyroglobulin.

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