scholarly journals Distinct Roles of Deiodinases on the Phenotype of Mct8 Defect: A Comparison of Eight Different Mouse Genotypes

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1180-1191 ◽  
Author(s):  
Xiao-Hui Liao ◽  
Caterina Di Cosmo ◽  
Alexandra M. Dumitrescu ◽  
Arturo Hernandez ◽  
Jacqueline Van Sande ◽  
...  
Keyword(s):  
Growth Response ◽  
Pituitary Thyroid Axis ◽  
Severe Impairment ◽  
Serum T3 ◽  
Serum T4 ◽  
Thyroid Axis ◽  
Mct8 Deficiency ◽  
The Brain ◽  
Insight Into ◽  
Serum Tsh

Mice deficient in the thyroid hormone (TH) transporter Mct8 (Mct8KO) have increased 5′-deiodination and impaired TH secretion and excretion. These and other unknown mechanisms result in the low-serum T4, high T3, and low rT3 levels characteristic of Mct8 defects. We investigated to what extent each of the 5′-deiodinases (D1, D2) contributes to the serum TH abnormalities of the Mct8KO by generating mice with all combinations of Mct8 and D1 and/or D2 deficiencies and comparing the resulting eight genotypes. Adding D1 deficiency to that of Mct8 corrected the serum TH abnormalities of Mct8KO mice, normalized brain T3 content, and reduced the impaired expression of TH-responsive genes. In contrast, Mct8D2KO mice maintained the serum TH abnormalities of Mct8KO mice. However, the serum TSH level increased 27-fold, suggesting a severely impaired hypothalamo-pituitary-thyroid axis. The brain of Mct8D2KO manifested a pattern of more severe impairment of TH action than Mct8KO alone. In triple Mct8D1D2KO mice, the markedly increased serum TH levels produced milder brain defect than that of Mct8D2KO at the expense of more severe liver thyrotoxicosis. Additionally, we observed that mice deficient in D2 had an unexplained marked reduction in the thyroid growth response to TSH. Our studies on these eight genotypes provide a unique insight into the complex interplay of the deiodinases in the Mct8 defect and suggest that D1 contributes to the increased serum T3 in Mct8 deficiency, whereas D2 mainly functions locally, converting T4 to T3 to compensate for distinct cellular TH depletion in Mct8KO mice.

Effect of winter sleep on pituitary-thyroid axis in American black bear.

1979 ◽  
Vol 237 (3) ◽  
pp. E227 ◽  
Author(s):  
F Azizi ◽  
J E Mannix ◽  
D Howard ◽  
R A Nelson
Keyword(s):  
Black Bear ◽  
Delayed Response ◽  
American Black Bear ◽  
Pituitary Thyroid Axis ◽  
Serum T3 ◽  
Serum T4 ◽  
Thyroid Axis ◽  
American Black ◽  
Maximum Increment ◽  
Winter Sleep

During winter sleep the black bear has decreased levels of serum total and free thyroxine (T4) and triiodothyronine (T3) and a prolonged, delayed response of serum thyrotropin (TSH) (bioassay) to thyrotropin-releasing hormone (TRH). Four weeks after the end of winter sleep, levels of serum thyroid hormones increase, and TSH response to TRH is short and brisk. Serum T4 and T3 rise after TRH administration both during and after winter sleep; however, the maximum increment in serum T3 is greater during winter sleep when the TSH rise is also prolonged and exaggerated. These observations suggest that transient hypothyroidism of possible hypothalamic origin occurs in bears during winter sleep.

scholarly journals Disruption of neuromedin B receptor gene results in dysregulation of the pituitary–thyroid axis

2006 ◽  
Vol 36 (1) ◽  
pp. 73-80 ◽  
Author(s):  
K J Oliveira ◽  
T M Ortiga-Carvalho ◽  
A Cabanelas ◽  
M A L C Veiga ◽  
K Aoki ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Receptor Subtype ◽  
Type I ◽  
Mrna Levels ◽  
Neuromedin B ◽  
Pituitary Thyroid Axis ◽  
Tsh Secretion ◽  
Serum T3 ◽  
Thyroid Axis ◽  
Serum Tsh

The level of thyrotropin (TSH) secretion is determined by the balance of TSH-releasing hormone (TRH) and thyroid hormones. However, neuromedin B (NB), a bombesin-like peptide, highly concentrated in the pituitary, has been postulated to be a tonic inhibitor of TSH secretion. We studied the pituitary–thyroid axis in adult male mice lacking NB receptor (NBR-KO) and their wild-type (WT) littermates. At basal state, NBR-KO mice presented serum TSH slightly higher than WT (18%, P< 0.05), normal intra-pituitary TSH content, and no significant changes in α and β TSH mRNA levels. Serum thyroxine was normal but serum triiodothyronine (T3) was reduced by 24% (P< 0.01) in NBR-KO mice. Pituitaries of NBR-KO mice exhibited no alteration in prolactin mRNA expression but type I and II deiodinase mRNA levels were reduced by 53 and 42% respectively (P< 0.05), while TRH receptor mRNA levels were importantly increased (78%, P< 0.05). The TSH-releasing effect of TRH was significantly higher in NBR-KO than in WT mice (7.1-and 4.0-fold respectively), but, while WT mice presented a 27% increase in serum T3 (P< 0.05) after TRH, NBR-KO mice showed no change in serum T3 after TRH. NBR-KO mice did not respond to exogenous NB, while WT showed a 30% reduction in serum TSH. No compensatory changes in mRNA expression of NB or other bombesin-related peptides and receptors (gastrin-releasing peptide (GRP), GRP-receptor and bombesin receptor subtype-3) were found in the pituitary of NBR-KO mice. Therefore, the data suggest that NB receptor pathways are importantly involved in thyrotroph gene regulation and function, leading to a state where TSH release is facilitated especially in response to TRH, but probably with a less-bioactive TSH. Therefore, the study highlights the important role of NB as a physiological regulator of pituitary–thyroid axis function and gene expression.

The Role of Tanycytes in the Hypothalamus-Pituitary-Thyroid Axis and the Possibilities for Their Genetic Manipulation

2019 ◽  
Vol 128 (06/07) ◽  
pp. 388-394
Author(s):  
Helge Müller-Fielitz ◽  
Markus Schwaninger
Keyword(s):  
Energy Homeostasis ◽  
Genetic Manipulation ◽  
Heart Function ◽  
Feedback Regulation ◽  
Target Organs ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Hpt Axis ◽  
The Brain

AbstractThyroid hormone (TH) regulation is important for development, energy homeostasis, heart function, and bone formation. To control the effects of TH in target organs, the hypothalamus-pituitary-thyroid (HPT) axis and the tissue-specific availability of TH are highly regulated by negative feedback. To exert a central feedback, TH must enter the brain via specific transport mechanisms and cross the blood-brain barrier. Here, tanycytes, which are located in the ventral walls of the 3rd ventricle in the mediobasal hypothalamus (MBH), function as gatekeepers. Tanycytes are able to transport, sense, and modify the release of hormones of the HPT axis and are involved in feedback regulation. In this review, we focus on the relevance of tanycytes in thyrotropin-releasing hormone (TRH) release and review available genetic tools to investigate the physiological functions of these cells.

scholarly journals Inhibition of pituitary type 2 deiodinase by reverse triiodothyronine does not alter thyroxine-induced inhibition of thyrotropin secretion in hypothyroid rats

2005 ◽  
Vol 153 (3) ◽  
pp. 429-434 ◽  
Author(s):  
P Cettour-Rose ◽  
T J Visser ◽  
A G Burger ◽  
F Rohner-Jeanrenaud
Keyword(s):  
Specific Inhibitor ◽  
Adult Rats ◽  
Reverse T3 ◽  
Brown Adipose ◽  
Tsh Secretion ◽  
Serum T3 ◽  
Serum T4 ◽  
Serum Tsh ◽  
Tsh Levels

Objectives: Intrapituitary triiodothyronine (T3) production plays a pivotal role in the control of TSH secretion. Its production is increased in the presence of decreased serum thyroxine (T4) concentrations and the enzyme responsible, deiodinase type 2 (D2), is highest in hypothyroidism. In order to document the role of this enzyme in adult rats we developed an experimental model that inhibited this enzyme using the specific inhibitor, reverse T3 (rT3). Methods: Hypothyroidism was induced with propylthiouracil (PTU; 0.025 g/l in drinking water) which in addition blocked deiodinase type 1 (D1) activity, responsible for the rapid clearance of rT3 in vivo. During the last 7 days of the experiment, the hypothyroid rats were injected (s.c.) for 4 days with 0.4 or 0.8 nmol T4 per 100 g body weight (bw) per day. For the last 3 days, the same amount of T4 was infused via s.c. minipumps. In additional groups, 25 nmol rT3/100 g bw per day were added to the 3-day infusion of T4. Results: Infusion of 0.4 nmol T4/100 g bw per day did not affect the high serum TSH levels, 0.8 nmol T4/100 g bw per day decreased them to 57% of the hypothyroid values. The infusions of rT3 inhibited D2 activity in all organs where it was measured: the pituitary, brain cortex and brown adipose tissue (BAT). In the pituitary, the activity was 27%, to less than 15% of the activity in hypothyroidism. Despite that, serum TSH levels did not increase, serum T4 concentrations did not change and the changes in serum T3 were minimal. Conclusions: We conclude that in partly hypothyroid rats, a 3-day inhibition of D2 activity, without concomitant change in serum T4 and minimal changes in serum T3 levels, is not able to upregulate TSH secretion and we postulate that this may be a reflection of absent or only minimal changes in circulating T3 concentrations.

scholarly journals The Hypothalamic-Pituitary-Thyroid Axis in Preterm Infants; Changes in the First 24 Hours of Postnatal Life

2004 ◽  
Vol 89 (6) ◽  
pp. 2824-2831 ◽  
Author(s):  
Nuala Murphy ◽  
Robert Hume ◽  
Hans van Toor ◽  
Tom G. Matthews ◽  
Simon A. Ogston ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Age Groups ◽  
Postnatal Life ◽  
Free T4 ◽  
Thyroxine Binding Globulin ◽  
Time Points ◽  
Pituitary Thyroid Axis ◽  
Serum T4 ◽  
Thyroid Axis ◽  
Immature Group

Abstract The purpose of this study was to measure serum T4, free T4, TSH, T3, rT3, T4 sulfate, and thyroxine binding globulin at four time points within the first 24 h of life (cord and 1, 7, and 24 h) in infants between 24 and 34 wk gestation. The infants were subdivided into gestational age groups: 24–27 wk (n = 22); 28–30 wk (n = 26); and 31–34 wk (n = 24). The TSH surge in the first hour of postnatal life was markedly attenuated in infants of 24–27 wk gestation [8 compared with 20 (28–30 wk) and 23 mU/liter (31–34 wk)]. T4 levels in the most immature group declined over the first 24 h, whereas levels increased in the more mature groups [mean cord and 24-h levels: 65 and 59 (NS) vs. 70 and 84 (P &lt; 0.002) vs. 98 and 125 (NS) nmol/liter]. Free T4 and T3 showed only small, transient increases in the most immature group and progressively larger and sustained increases in the other gestational groups. rT3 and T4 sulfate levels in cord serum were higher in the most immature infants, and in all groups levels decreased initially and then variably increased. The features of a severely attenuated or failed hypothalamic-pituitary-thyroid response to delivery critically define this 24- to 27-wk group as distinct from more mature preterm infants.

Influence of meal composition on the postprandial response of the pituitary–thyroid axis

1995 ◽  
Vol 133 (1) ◽  
pp. 75-79 ◽  
Author(s):  
Vinay Kamat ◽  
Wendy L Hecht ◽  
Robert T Rubin
Keyword(s):  
Significant Decline ◽  
Randomized Design ◽  
Postprandial Response ◽  
Pituitary Thyroid Axis ◽  
Tsh Secretion ◽  
Thyroid Axis ◽  
Normal Men ◽  
Allegheny General Hospital ◽  
Serum Tsh ◽  
Meal Composition

Kamat V, Hecht WL, Rubin RT. Influence of meal composition on the postprandial response of the pituitary–thyroid axis. Eur J Endocrinol 1995;133:75–9. ISSN 0804–4643 Ingestion of food can result in an acute decline of serum thyrotropin (TSH) concentrations, but it is not known whether meal composition and/or stomach distension are influential. Normal men and women were given a normocaloric or hypocaloric, isobulk meal at lunch and at dinner in a randomized design. The normocaloric, but not the isobulk, meal resulted in a significant decline in serum TSH at both lunch and dinner; thyroid hormones and cortisol were not affected significantly. These findings suggest that meal composition is influential in the acute postprandial decline of serum TSH in man. A possible mechanism is food-induced elevation of somatostatin and consequent suppression of TSH secretion. Robert T Rubin, Neurosciences Research Center, Allegheny General Hospital, 320 E North Ave. Pittsburgh, PA 15212-4772, USA

scholarly journals The pituitary-thyroid axis in healthy men living under subarctic climatological conditions

2001 ◽  
Vol 169 (1) ◽  
pp. 195-203 ◽  
Author(s):  
J Hassi ◽  
K Sikkila ◽  
A Ruokonen ◽  
J Leppaluoto
Keyword(s):  
Thyroid Hormones ◽  
Climatic Factors ◽  
Feedback Mechanism ◽  
Free Triiodothyronine ◽  
Serum Free ◽  
Healthy Men ◽  
Non Invasive ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Serum Tsh

In order to evaluate the effects of climatic factors on the secretion of thyroid hormones and TSH in a high latitude population, we have taken serum and urine samples from 20 healthy men from northern Finland (67 degrees -68 degrees N) every 2 months for a period of 14 months. Serum free triiodothyronine (T(3)) levels were lower in February than in August (3.9 vs 4.4 pmol/l, P<0.05) and TSH levels were higher in December than during other months (2.1 vs 1.5-1.7 mU/l, P<0.01). Serum total and free thyroxine (T(4)), total T(3) and reverse T(3) levels and urinary T(4) levels were unchanged. Urinary T(3) levels were significantly higher in winter than in summer. Serum free T(3) correlated highly significantly with the outdoor temperature integrated backwards weekly for 7-56 days (r=0.26 for 1-56 days) from the day when the blood samples were taken. Serum TSH did not show any significant correlation with the thyroid hormones or with the integrated temperature of the previous days, but it did show an inverse and significant correlation (r=-0.31) with the ambient luminosity integrated backwards for 7 days from the day when the blood sample was taken. The gradually increasing correlation between outdoor temperatures and serum free T(3) suggests that the disposal of thyroid hormones is accelerated in winter, leading to low serum free T(3) levels and a high urinary free T(3) excretion. Since there was no correlation between thyroid hormones and serum TSH, the feedback mechanism between TSH and thyroid hormones may not be the only contributing factor, and other factors such as ambient luminosity may at least partly determine serum TSH in these conditions. Also urinary free T(3) appears to be a novel and non-invasive indicator for thyroid physiology.

Serum concentrations of thyrotropin, thyroxine, triiodothyronine and thyroxine binding globulin in female endurance runners and joggers

1987 ◽  
Vol 114 (1) ◽  
pp. 41-46 ◽  
Author(s):  
H. Hohtari ◽  
A. Pakarinen ◽  
A. Kauppila
Keyword(s):  
Endurance Training ◽  
Anterior Pituitary ◽  
Luteal Phase ◽  
Serum Concentrations ◽  
Endurance Running ◽  
Thyroxine Binding Globulin ◽  
Trh Stimulation ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Serum Tsh

Abstract. The effects of endurance training and season on the function of the anterior pituitary-thyroid axis were studied in 18 female runners and their 12 controls, and in 13 joggers and their 11 controls in Northern Finland, with a large seasonal difference in environmental factors. The serum concentrations of thyrotropin (TSH), thyroxine (T4), free thyroxine (fT4), triiodothyronine (T3), thyroxine binding globulin (TBG) and oestradiol (E2) were measured during one menstrual cycle in the light training season (autumn) and in the hard training season (spring). The responses of TSH to intravenous TRH stimulation were also measured in the luteal phase of the cycle during the hard training season. Endurance running did not affect the basal or TRH-stimulated serum TSH concentrations, while those of T4 and fT4 in runners were lowered in both seasons and that of T3 in the light training season in relation to control subjects. The serum concentrations of TBG were also significantly lower in runners than their controls in the luteal phase in both seasons. The effect of jogging on thyroid hormones was less pronounced. Serum concentrations of TSH, T4, fT4, T3 and TBG were generally slightly higher in spring than in autumn. Strenuous endurance training seems to have minor changes on the function of the thyroid gland. Depressed T4 levels in runners may rather be due to lowered TBG levels than due to direct effect of training. In spring the function of anterior pituitary-thyroid axis is more active than in autumn.

scholarly journals Type 3 Deiodinase Deficiency Results in Functional Abnormalities at Multiple Levels of the Thyroid Axis

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5680-5687 ◽  
Author(s):  
Arturo Hernandez ◽  
M. Elena Martinez ◽  
Xiao-Hui Liao ◽  
Jacqueline Van Sande ◽  
Samuel Refetoff ◽  
...  
Keyword(s):  
Wild Type ◽  
Central Hypothyroidism ◽  
Trh Stimulation ◽  
Serum T3 ◽  
Antithyroid Treatment ◽  
Pituitary Glands ◽  
Thyroid Axis ◽  
Type 3 ◽  
Serum Tsh ◽  
Hormonal Levels

The type 3 deiodinase (D3) is a selenoenzyme that inactivates thyroid hormones and is highly expressed during development and in the adult central nervous system. We have recently observed that mice lacking D3 activity (D3KO mice) develop perinatal thyrotoxicosis followed in adulthood by a pattern of hormonal levels that is suggestive of central hypothyroidism. In this report we describe the results of additional studies designed to investigate the regulation of the thyroid axis in this unique animal model. Our results demonstrate that the thyroid and pituitary glands of D3KO mice do not respond appropriately to TSH and TRH stimulation, respectively. Furthermore, after induction of severe hypothyroidism by antithyroid treatment, the rise in serum TSH in D3KO mice is only 15% of that observed in wild-type mice. In addition, D3KO animals rendered severely hypothyroid fail to show the expected increase in prepro-TRH mRNA in the paraventricular nucleus of the hypothalamus. Finally, treatment with T3 results in a serum T3 level in D3KO mice that is much higher than that in wild-type mice. This is accompanied by significant weight loss and lethality in mutant animals. In conclusion, the absence of D3 activity results in impaired clearance of T3 and significant defects in the mechanisms regulating the thyroid axis at all levels: hypothalamus, pituitary, and thyroid.

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