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.

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.

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 Diminished and irregular TSH secretion with delayed acrophase in patients with Cushing's syndrome

2009 ◽  
Vol 161 (5) ◽  
pp. 695-703 ◽  
Author(s):  
Ferdinand Roelfsema ◽  
Alberto M Pereira ◽  
Nienke R Biermasz ◽  
Marijke Frolich ◽  
Daniel M Keenan ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Approximate Entropy ◽  
Pituitary Surgery ◽  
Pulse Frequency ◽  
Cushing's Syndrome ◽  
Pituitary Thyroid Axis ◽  
Tsh Secretion ◽  
Thyroid Axis ◽  
Serum Tsh ◽  
Active Disease

ContextThe hypothalamus–pituitary–thyroid axis in Cushing's syndrome may be altered. Previous reports have shown diminished serum TSH concentration and decreased response to TRH.ObjectiveWe analyzed serum TSH profiles in relation to cortisol profiles in patients with hypercortisolism of pituitary (n=16) or primary-adrenal origin (n=11) and after remission by pituitary surgery (n=7) in order to delineate aberrations in the hypothalamus–pituitary–thyroid system.InterventionPatients and controls (n=27) underwent a 24-h blood sampling study. Serum TSH and cortisol were measured with precise methods, and data were analyzed with a deconvolution program, approximate entropy (ApEn), and cosinor regression.ResultsPulsatile TSH secretion and mean TSH pulse mass were diminished during hypercortisolism, independently of etiology (P<0.001). TSH secretion was increased in patients in remission only during daytime due to increased basal secretion (P<0.01). Pulse frequency and half life of TSH were similar in patients and controls. TSH ApEn (irregularity) was increased in patients with hypercortisolism (P<0.01), but was normal in cured patients. Cross-ApEn between TSH and cortisol, a measure of pattern synchrony loss, was increased in active disease, indicating (partial) loss of secretory synchrony. The TSH rhythm was phase delayed in hypercortisolemic patients, but normal in cured patients (P<0.01). Free thyroxine levels were decreased only in pituitary-dependent hypercortisolism compared with controls (P=0.003). Total 24-h TSH correlated negatively and linearly with log-transformed cortisol secretion (R=0.43, P=0.001).ConclusionCortisol excess decreases TSH secretion by diminishing pulsatile release, whereas surgically cured patients have elevated nonpulsatile TSH release. Diminished TSH secretory regularity in active disease suggests glucocorticoid-induced dysregulation of TRH or somatostatinergic/annexin-1 control.

The hypothalamic-pituitary-thyroid axis in Type 1 diabetes: influence of diabetic metabolic control

1984 ◽  
Vol 106 (1) ◽  
pp. 92-96 ◽  
Author(s):  
I. A. MacFarlane ◽  
M. C. Sheppard ◽  
E. G. Black ◽  
S. Gilbey ◽  
A. D. Wright
Keyword(s):  
Metabolic Control ◽  
Thyroid Function ◽  
Fasting Blood Glucose ◽  
Type I ◽  
Poor Metabolic Control ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Insulin Dependent ◽  
Serum Tsh

Abstract. The influence of diabetic metabolic control on indices of thyroid function was studied in 9 euthyroid, insulin-dependent (Type 1) diabetics. During chronic poor metabolic control (mean fasting blood glucose 13 mmol/l and HbA1 concentrations 14.7%) serum T3 concentrations were low (P < 0.01) while serum T4 and basal TSH concentrations were normal. After 6–8 weeks of improved metabolic control, mean HbA1 concentrations had fallen to 10.7% (P < 0.01) and serum T3 concentrations had increased into the normal range. Serum T4 and basal TSH concentrations were unchanged. The serum TSH response to iv TRH remained normal throughout the study. In Type I diabetics, with chronic poor metabolic control, the serum T4 concentration and the TSH response to TRH are therefore appropriate indicators of thyroid function.

scholarly journals Interleukin-18, a proinflammatory cytokine, contributes to the pathogenesis of non-thyroidal illness mainly via the central part of the hypothalamus-pituitary-thyroid axis

2004 ◽  
pp. 497-502 ◽  
Author(s):  
A Boelen ◽  
J Kwakkel ◽  
M Platvoet-ter Schiphorst ◽  
B Mentrup ◽  
A Baur ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Proinflammatory Cytokine ◽  
Biological Properties ◽  
Thyroid Hormone Metabolism ◽  
Pituitary Thyroid Axis ◽  
Serum T3 ◽  
Thyroid Axis ◽  
Hpt Axis

OBJECTIVE: Proinflammatory cytokines are involved in the pathogenesis of non-thyroidal illness (NTI), as shown by studies with IL-6-/- and IL-12-/- mice. Interleukin (IL)-6 changes peripheral thyroid hormone metabolism, and IL-12 seems to be involved in the regulation of the central part of the hypothalamic-pituitary-thyroid (HPT) axis during illness. IL-18 is a proinflammatory cytokine which shares important biological properties with IL-12, such as interferon (IFN)-gamma-inducing activity. DESIGN: By studying the changes in the HPT-axis during bacterial lipopolysaccharide (LPS)-induced illness in IL-18-/-, IFNgammaR-/- and wild-type (WT) mice, we wanted to unravel the putative role of IL-18 and IFNgamma in the pathogenesis of NTI. RESULTS: LPS induced a decrease in pituitary type 1 deiodinase (D1) activity (P<0.05, ANOVA) in WT mice, but not in IL-18-/- mice, while the decrease in D2 activity was similar in both strains. LPS decreased serum thyroid hormone levels and liver D1 mRNA within 24 h similarly in IL-18-/-, and WT mice. The expression of IL-1, IL-6 and IFNgamma mRNA expression was significantly lower in IL-18-/- mice than in WT, while IL-12 mRNA expression was similar. IFNgammaR-/- mice had higher basal D1 activity in the pituitary than WT mice (P<0.05); LPS induced a decrease of D2, but not of D1, activity in the pituitary which was similar in both strains. In the liver, the LPS-induced increase in cytokine expression was not different between IFNgammaR-/- mice and WT mice, and the decrease in serum T3 and T4 levels and hepatic D1 mRNA was also similar. CONCLUSIONS: The relative decrease in serum T3 and T4 and liver D1 mRNA in response to LPS is similar in IL-18-/-, IFNgammaR-/- and WT mice despite significant changes in hepatic cytokine induction. However, the LPS-induced decrease in D1 activity in the pituitary of WT mice is absent in IL-18-/- mice; in contrast, LPS did not decrease pituitary D1 activity in the IFNgammaR-/- mice or their WT, which might be due to the genetic background of the mice. Our results suggest that IL-18 is also involved in the regulation of the central part of the HPT axis during illness.

scholarly journals Placental Iodothyronine Deiodinases Expression in Pregnant Cows Exposed to Propylthiouracil (Ptu) and Thyroid Axis Activity of their Calves

2016 ◽  
Vol 66 (1) ◽  
pp. 61-75 ◽  
Author(s):  
Danijela Kirovski ◽  
Petar Dodovski ◽  
Đorđe Savić ◽  
Ivan Vujanac ◽  
Radiša Prodanović ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Placental Tissue ◽  
Pcr Analysis ◽  
Type I ◽  
Mrna Levels ◽  
Prenatally Exposed ◽  
Bovine Placenta ◽  
Iodothyronine Deiodinases ◽  
Thyroid Axis ◽  
First Time

AbstractThe aim of our study was to investigate if the thyroid axis of newborn calves is affected by prenatal application of propylthyouracil (PTU). The study included 20 late pregnant Holstein cows. One group (n=10) was treated with PTU (4 mg/kg of BW daily) from day 20 before expected calving until the day of calving. The other group (n=10) was non-treated. Placental samples of dams were obtained for measuring mRNA expression of iodothyronine deiodinases type I (D1), type II (D2) and type III (D3). After parturition calves were separated from the dams and included in the study. Blood samples were taken daily from each calf starting on the day of birth until day 7 of age. Blood T3, T4and TSH concentrations were measured. PCR analysis of the placental tissue revealed an abundance of all three types of placental deiodinases in non-treated cows, and a significant elevation of mRNA levels for all three types of deiodinases after PTU treatment. Calves that originated from dams treated with PTU had significantly lower T3and T4and significantly higher TSH concentrations compared to non-treated calves during the first 2 days of life. Starting from day 4 until day 6 of life the opposite effect was observed meaning that calves prenatally exposed to PTU had significantly higher T3and T4and slightly lower TSH. Our study, for the first time, provides information related to iodothyronine deiodinases mRNA expression in bovine placenta, and confirm that PTU treatment of pregnant dams provokes depression of thyroid function in newborns during the first days of life.

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 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.

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.

INHIBITED HYPOTHALAMIC-PITUITARY-THYROID AXIS IN TYPE I PSEUDOHYPOPARATHYROIDISM

1999 ◽  
Vol 5 (2) ◽  
pp. 61-65 ◽  
Author(s):  
Udaya M. Kabadi, MD, FACE, FRCP(C), FACP ◽  
Robert P. Cech, MD
Keyword(s):  
Type I ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis
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