scholarly journals Type 3 Deiodinase Role on Central Thyroid Hormone Action Affects the Leptin-Melanocortin System and Circadian Activity

Endocrinology ◽  
2016 ◽  
Vol 158 (2) ◽  
pp. 419-430 ◽  
Author(s):  
Zhaofei Wu ◽  
M. Elena Martinez ◽  
Donald L. St. Germain ◽  
Arturo Hernandez
Keyword(s):  
Energy Balance ◽  
Elevated Serum ◽  
Serum Levels ◽  
Leptin Resistance ◽  
Melanocortin System ◽  
White Adipocyte ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
The Central Nervous System ◽  
Type 3

Abstract The role of thyroid hormones (THs) in the central regulation of energy balance is increasingly appreciated. Mice lacking the type 3 deiodinase (DIO3), which inactivates TH, have decreased circulating TH levels relative to control mice as a result of defects in the hypothalamic-pituitary-thyroid axis. However, we have shown that the TH status of the adult Dio3−/− brain is opposite that of the serum, exhibiting enhanced levels of TH action. Because the brain, particularly the hypothalamus, harbors important circuitries that regulate metabolism, we aimed to examine the energy balance phenotype of Dio3−/− mice and determine whether it is associated with hypothalamic abnormalities. Here we show that Dio3−/− mice of both sexes exhibit decreased adiposity, reduced brown and white adipocyte size, and enhanced fat loss in response to triiodothyronine (T3) treatment. They also exhibit increased TH action in the hypothalamus, with abnormal expression and T3 sensitivity of genes integral to the leptin-melanocortin system, including Agrp, Npy, Pomc, and Mc4r. The normal to elevated serum levels of leptin, and elevated and repressed expression of Agrp and Pomc, respectively, suggest a profile of leptin resistance. Interestingly, Dio3−/− mice also display elevated locomotor activity and increased energy expenditure. This occurs in association with expanded nighttime activity periods, suggesting a disrupted circadian rhythm. We conclude that DIO3-mediated regulation of TH action in the central nervous system influences multiple critical determinants of energy balance. Those influences may partially compensate each other, with the result likely contributing to the decreased adiposity observed in Dio3−/− mice.

Investigations into the influence of the central nervous system on the pituitary-thyroid axis

Neurology ◽  
1966 ◽  
Vol 16 (12) ◽  
pp. 1166-1166
Author(s):  
W. C. Boop ◽  
M. C. ◽  
J. Story
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
The Central Nervous System

The effect of iodine deficiency and propylthiouracil on the hypothalamo–pituitary–thyroid axis in the neonatal rat

1978 ◽  
Vol 56 (6) ◽  
pp. 950-955 ◽  
Author(s):  
J. H. Dussault ◽  
P. Walker
Keyword(s):  
Tap Water ◽  
Elevated Serum ◽  
Thyroid Stimulating Hormone ◽  
Significant Decline ◽  
Neonatal Rat ◽  
Rapid Rise ◽  
Neonatal Rats ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Serum Tsh

The effect of chronic propylthiouracil (PTU) and low iodide diet (LID) on the development of the hypothalamo–pituitary–thyroid axis in the rat has been studied. Pregnant and neonatal rats received 0.05% PTU in their drinking water or LID (distilled water and LID: Teklad Mills, Madison, Wisconsin). Control animals received tap water and Purina rat chow ad libitum. Hypothalamic thyrotropin-releasing hormone (TRH), pituitary and serum thyroid-stimulating hormone (THS), and serum thyroxine (T4) and triiodothyronine (T3) were measured by specific double-antibody radioimmunoassay. Both PTU- and LID-exposed animals had low hypothalamic TRH concentrations at 1 day and a rapid rise to peak levels of 2.4 ± 0.4 pg/μg protein (mean ± SEM) between 12 and 24 days in the PTU animals and 3.2 ± 0.4 pg/μg protein between 12 and 18 days in the LID rats. Hypothalamic TRH concentrations remained relatively stable in the PTU animals, whereas in the LID rats, after a brief but significant decline from 24 to 28 days, hypothalamic TRH concentrations rose to the highest values observed at 57 days (3.9 ± 0.5 pg/μg protein). Both groups of animals had elevated serum TSH levels at 1 day, with higher values seen in the PTU group (p < 0.01), and both showed a rapid rise at 12 days. Thereafter, serum TSH concentrations remained high in the PTU rats but declined to stable, albeit elevated, levels by 24 days (1260 ± 140 ng/ml) in the LID animals. Hypothyroidism was confirmed in the PTU animals by undetectable T4 and reduced T3 concentrations. In the LID rats, serum T4 concentrations rose from undetectable levels at 1 day to stable values by 32 days (2.18 ± 0.13 μg/dl). Serum T3 rose to peak values of 157.0 ± 6.9 ng/dl at 32 days and was elevated at all times after 12 days. These data suggest that chronic exposure to PTU or LID results in a marked derangement of the ontogenetic pattern of the hypothalamo–pituitary–thyroid axis. In addition, neonatal rats exposed to LID appear to respond appropriately by preferential T3 production.

scholarly journals Interactions between the melanocortin system and the hypothalamo–pituitary–thyroid axis

Peptides ◽  
2006 ◽  
Vol 27 (2) ◽  
pp. 333-339 ◽  
Author(s):  
Niamh M. Martin ◽  
Kirsty L. Smith ◽  
Stephen R. Bloom ◽  
Caroline J. Small
Keyword(s):  
Melanocortin System ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis

Postnatal development of brain TRH, serum TSH and thyroid hormones in the male and female rat

1986 ◽  
Vol 112 (1) ◽  
pp. 7-11 ◽  
Author(s):  
L. Gayo ◽  
B. Bonet ◽  
A. S. Herranz ◽  
R. Iglesias ◽  
M.J. Toro ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Thyroid Hormones ◽  
Postnatal Development ◽  
Female Rat ◽  
Male And Female ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
The Central Nervous System ◽  
Serum Tsh

Abstract. The postnatal development of immunoreactive TRH in the central nervous system (CNS), serum TSH and thyroid hormones was studied in both male and female normal rats. While in most structures of the CNS, TRH increased until day 20–30, serum TSH values peaked at day 15 as did T4. Significant differences were also obtained between both sexes in these parameters. These data further support the fact that pituitary-thyroid axis maturation is independent of brain TRH.

scholarly journals Type 3 Deiodinase Deficiency Causes Spatial and Temporal Alterations in Brain T3 Signaling that Are Dissociated from Serum Thyroid Hormone Levels

Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5550-5558 ◽  
Author(s):  
Arturo Hernandez ◽  
Laure Quignodon ◽  
M. Elena Martinez ◽  
Frederic Flamant ◽  
Donald L. St. Germain
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Elevated Serum ◽  
Adult Brain ◽  
Neural Function ◽  
Peripheral Tissues ◽  
Show Evidence ◽  
The Central Nervous System ◽  
Type 3 ◽  
The Brain

The type 3 deiodinase (D3) is an enzyme that inactivates thyroid hormones (TH) and is highly expressed during development and in the central nervous system. D3-deficient (D3KO) mice develop markedly elevated serum T3 level in the perinatal period. In adulthood, circulating T4 and T3 levels are reduced due to functional deficits in the thyroid axis and peripheral tissues (i.e. liver) show evidence of decreased TH action. Given the importance of TH for brain development, we aimed to assess TH action in the brain of D3KO mice at different developmental stages and determine to what extent it correlates with serum TH parameters. We used a transgenic mouse model (FINDT3) that expresses the reporter gene β-galactosidase (β-gal) in the central nervous system as a readout of local TH availability. Together with experiments determining expression levels of TH-regulated genes, our results show that after a state of thyrotoxicosis in early development, most regions of the D3KO brain show evidence of decreased TH action at weaning age. However, later in adulthood and in old age, the brain again manifests a thyrotoxic state, despite reduced serum TH levels. These region-specific changes in brain TH status during the life span of the animal provide novel insight into the important role of the D3 in the developing and adult brain. Our results suggest that, even if serum concentrations of TH are normal or low, impaired D3 activity may result in excessive TH action in multiple brain regions, with potential consequences of altered neural function that may be of clinical relevance to neurological and neuroendocrine disorders.

Mild hyperthyroidism with inappropriate secretion of TSH in postmenopausal women

1986 ◽  
Vol 111 (2) ◽  
pp. 204-208 ◽  
Author(s):  
N. Custro ◽  
V. Scafidi
Keyword(s):  
Thyroid Hormones ◽  
Postmenopausal Women ◽  
Present Report ◽  
Serum Levels ◽  
Suppressive Effect ◽  
Pituitary Thyroid Axis ◽  
Tsh Secretion ◽  
Thyroid Axis ◽  
Suppression Test ◽  
Inappropriate Tsh Secretion

Abstract. In a previous study on the function of the hypothalamus - pituitary - thyroid axis, about 10% of postmenopausal women with the climacteric syndrome were found to have borderline high values of T3 and T4 and signs of pituitary decreased sensitivity to the suppressive effect of increased thyroid hormones. The present report concerns 5 women in the first phase of their menopause who showed a mild hyperthyroidism under basal conditions and after suppression test with liothyronine. Each patient had borderline increased levels of serum total and free T4 and T3 and a marked TSH responsiveness to exogenous TRH. After liothyronine, the serum levels of T4, FT4, TSH and the responsiveness to TRH-test clearly decreased. These data suggest an inappropriate TSH secretion with a decreased pituitary sentitivity to thyroid hormones. These cases could represent a modification of the hypothalamus-pituitary-thyroid axis associated with that of the gonadal axis, secondary to the absence of rapid adaptation of neurotransmitters.

scholarly journals The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin

2000 ◽  
Vol 105 (7) ◽  
pp. 1005-1011 ◽  
Author(s):  
M.S. Kim ◽  
C.J. Small ◽  
S.A Stanley ◽  
D.G.A. Morgan ◽  
L.J. Seal ◽  
...  
Keyword(s):  
Melanocortin System ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis

scholarly journals Daily Variations in Type II Iodothyronine Deiodinase Activity in the Rat Brain as Controlled by the Biological Clock

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1418-1427 ◽  
Author(s):  
Andries Kalsbeek ◽  
Ruud M. Buijs ◽  
Rosalinde van Schaik ◽  
Ellen Kaptein ◽  
Theo J. Visser ◽  
...  
Keyword(s):  
Biological Clock ◽  
Plasma Corticosterone ◽  
Daily Rhythm ◽  
Type Ii ◽  
Iodothyronine Deiodinase ◽  
Daily Variations ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
The Central Nervous System

Type II deiodinase (D2) plays a key role in regulating thyroid hormone-dependent processes in, among others, the central nervous system (CNS) by accelerating the intracellular conversion of T4 into active T3. Just like the well-known daily rhythm of the hormones of the hypothalamo-pituitary-thyroid axis, D2 activity also appears to show daily variations. However, the mechanisms involved in generating these daily variations, especially in the CNS, are not known. Therefore, we decided to investigate the role the master biological clock, located in the hypothalamus, plays with respect to D2 activity in the rat CNS as well as the role of one of its main hormonal outputs, i.e. plasma corticosterone. D2 activity showed a significant daily rhythm in the pineal and pituitary gland as well as hypothalamic and cortical brain tissue, albeit with a different timing of its acrophase in the different tissues. Ablation of the biological clock abolished the daily variations of D2 activity in all four tissues studied. The main effect of the knockout of the suprachiasmatic nuclei (SCN) was a reduction of nocturnal peak levels in D2 activity. Moreover, contrary to previous observations in SCN-intact animals, in SCN-lesioned animals, the decreased levels of D2 activity are accompanied by decreased plasma levels of the thyroid hormones, suggesting that the SCN separately stimulates D2 activity as well as the hypothalamo-pituitary-thyroid axis.

A Study of Thyroid Function in Cancer Cachexia

1989 ◽  
Vol 75 (2) ◽  
pp. 185-188 ◽  
Author(s):  
Gabriele Tancini ◽  
Sandro Barni ◽  
Sergio Crispino ◽  
Franco Paolorossi ◽  
Paolo Lissoni
Keyword(s):  
Weight Loss ◽  
Cancer Patients ◽  
Cancer Cachexia ◽  
Serum Levels ◽  
Biologically Active ◽  
Advanced Cancer Patients ◽  
Oncologic Patients ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Low Levels

The mechanisms responsible for cancer cachexia have not yet been clarified. To further investigate the role played by the hypothalamic-pituitary-thyroid axis in cancer cachexia, we evaluated serum levels of T3, FT3, T4, FT4, TSH and TBG in a group of 26 cancer patients, 14 of whom showed cachexia, whereas the other 12 had a body weight within the normal range despite their advanced diseases. As controls, 58 healthy subjects and 11 patients with benign weight loss were included in the study. Low levels of both T3 and FT3 were observed in all patients with benign weight loss and in 9/12 advanced cancer patients who had no cancer cachexia. On the contrary, only 4/14 cachectic cancer patients presented decreased values of T3 and FT3. Moreover, the mean serum levels of T3 and FT3 in cachectic oncologic patients were significantly higher than those seen both in non-cachectic cancer patients and in patients with benign weight loss. Since T3 is the biologically active thyroid hormone, the lack of a decrease in its production might play a role in the pathogenesis of cancer cachexia.

scholarly journals Recent Advances in Hypertension

Hypertension ◽  
2021 ◽  
Author(s):  
Vanessa Oliveira ◽  
Anne E. Kwitek ◽  
Curt D. Sigmund ◽  
Lisa L. Morselli ◽  
Justin L. Grobe
Keyword(s):  
Blood Pressure ◽  
Energy Balance ◽  
Cardiovascular Health ◽  
Resting Metabolic Rate ◽  
Major Change ◽  
Leptin Resistance ◽  
Molecular Signaling ◽  
Melanocortin System ◽  
Feeding Behaviors ◽  
Ongoing Work

Obesity represents the single greatest ongoing roadblock to improving cardiovascular health. Prolonged obesity is associated with fundamental changes in the integrative control of energy balance, including the development of selective leptin resistance, which is thought to contribute to obesity-associated hypertension, and adaptation of resting metabolic rate (RMR) when excess weight is reduced. Leptin and the melanocortin system within the hypothalamus contribute to the control of both energy balance and blood pressure. While the development of drugs to stimulate RMR and thereby reverse obesity through activation of the melanocortin system has been pursued, most of the resulting compounds simultaneously cause hypertension. Evidence supports the concept that although feeding behaviors, RMR, and blood pressure are controlled through mechanisms that utilize similar molecular mediators, these mechanisms exist in anatomically dissociable networks. New evidence supports a major change in molecular signaling within AgRP (Agouti-related peptide) neurons of the arcuate nucleus of the hypothalamus during prolonged obesity and the existence of multiple distinct subtypes of AgRP neurons that individually contribute to control of feeding, RMR, or blood pressure. Finally, ongoing work by our laboratory and others support a unique role for AT 1 (angiotensin II type 1 receptor) within one specific subtype of AgRP neuron for the control of RMR. We propose that understanding the unique biology of the AT 1 -expressing, RMR-controlling subtype of AgRP neurons will help to resolve the selective dysfunctions in RMR control that develop during prolonged obesity and potentially point toward novel druggable antiobesity targets that will not simultaneously cause hypertension.

Sign in / Sign up

Export Citation Format

Share Document