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 ◽  
...  

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.

1982 ◽  
Vol 101 (4) ◽  
pp. 538-541 ◽  
Author(s):  
Vincenzo Pezzino ◽  
Giuseppe Distefano ◽  
Antonio Belfiore ◽  
Sebastiano Filetti ◽  
Domenico Mazzone ◽  
...  

Abstract. Anencephaly provides a unique model for studying endocrine functions in absence of hypothalamic influence. We previously reported that in anencephalic newborns both pituitary TSH-secreting cells and the thyroid were normal and were able to function if adequately stimulated. In order to verify if the normal development of the pituitary-thyroid axis in these infants depends on TRH of extrahypothalamic origin, we measured endogenous TRH levels in the clear fluid of a cyst of the cerebro-vasculosa in 4 anencephalic newborns. In these cysts we also injected 200 μg of synthetic TRH and evaluated TSH response in peripheral blood samples. Endogenous TRH was detectable in the cysts of the cerebro-vasculosa in 3 of the 4 infants. In all 4 cases serum TSH sharply increased after TRH administration. Our data suggest that the normal development of the pituitary-thyroid axis in anencephalic infants either requires no TRH or depends on extrahypothalamic TRH. In this latter case TRH produced by other areas of the central nervous system might be secreted into the cysts of the cerebro-vasculosa, actively transported to the hypophyseal vessels, and might thus reach the pituitary to stimulate TSH-cells growth and function.


2021 ◽  
Vol 80 (3) ◽  
pp. 567-578 ◽  
Author(s):  
Rosaria Sciarrillo ◽  
Mariana Di Lorenzo ◽  
Salvatore Valiante ◽  
Luigi Rosati ◽  
Maria De Falco

Abstract Different environmental contaminants disturb the thyroid system at many levels. AlkylPhenols (APs), by-products of microbial degradation of AlkylPhenol Polyethoxylates (APEOs), constitute an important class of Endocrine Disrupting Chemicals (EDCs), the two most often used environmental APs being 4-nonylphenol (4-NP) and 4-tert-octylphenol (4-t-OP). The purpose of the present study was to investigate the effects on the thyroid gland of the bioindicator Podarcis siculus of OP alone and in combination with NP. We used radioimmunoassay to determine their effects on plasma 3,3′,5-triiodo-L-thyronine (T3), 3,3′,5,5′-L-thyroxine (T4), thyroid-stimulating hormone (TSH), and thyrotropin-releasing hormone (TRH) levels in adult male lizards. We also investigated the impacts of AP treatments on hepatic 5′ORD (type II) deiodinase and hepatic content of T3 and T4. After OP and OP + NP administration, TRH levels increased, whereas TSH, T3, and T4 levels decreased. Lizards treated with OP and OP + NP had a higher concentration of T3 in the liver and 5′ORD (type II) activity, whereas T4 concentrations were lower than that observed in the control group. Moreover, histological examination showed that the volume of the thyroid follicles became smaller in treated lizards suggesting that that thyroid follicular epithelial cells were not functionally active following treatment. This data collectively suggest a severe interference with hypothalamus–pituitary–thyroid axis and a systemic imbalance of thyroid hormones. Graphic Abstract


2019 ◽  
Vol 128 (06/07) ◽  
pp. 388-394
Author(s):  
Helge Müller-Fielitz ◽  
Markus Schwaninger

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.


Endocrinology ◽  
2016 ◽  
Vol 158 (2) ◽  
pp. 419-430 ◽  
Author(s):  
Zhaofei Wu ◽  
M. Elena Martinez ◽  
Donald L. St. Germain ◽  
Arturo Hernandez

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.


2005 ◽  
Vol 281 (8) ◽  
pp. 5000-5007 ◽  
Author(s):  
Amisra A. Nikrodhanond ◽  
Tania M. Ortiga-Carvalho ◽  
Nobuyuki Shibusawa ◽  
Koshi Hashimoto ◽  
Xiao Hui Liao ◽  
...  

2002 ◽  
Vol 174 (1) ◽  
pp. 121-125 ◽  
Author(s):  
TM Ortiga-Carvalho ◽  
KJ Oliveira ◽  
BA Soares ◽  
CC Pazos-Moura

Leptin has been shown to stimulate the hypothalamus-pituitary-thyroid axis in fasting rodents; however, its role in thyroid axis regulation under physiological conditions is still under investigation. Here it was investigated in freely fed rats whether leptin modulates thyrotroph function in vivo and whether leptin has direct pituitary effects on TSH release. Since leptin is produced in the pituitary, the possibility was also investigated that leptin may be a local regulator of TSH release. TSH was measured by specific RIA. Freely fed adult rats 2 h after being injected with a single s.c. injection of 8 microg leptin/100 g body weight showed a 2-fold increase in serum TSH (P<0.05). Hemi-pituitary explants incubated with 10(-9) and 10(-7) M leptin for 2 h showed a reduced TSH release of 40 and 50% respectively (P<0.05). Conversely, incubation of hemi-pituitary explants with antiserum against leptin, aiming to block the action of locally produced leptin, resulted in higher TSH release (45%, P<0.05). In conclusion, also in the fed state, leptin has an acute stimulatory effect on TSH release in vivo, acting probably at the hypothalamus. However, the direct pituitary effect of leptin is inhibitory and data also provide evidence that in the rat pituitary leptin may act as an autocrine/paracrine inhibitor of TSH release.


1979 ◽  
Vol 55 (6) ◽  
pp. 776-786
Author(s):  
Masatomo MORI ◽  
Kihachi OHSHIMA ◽  
Sakae MARUTA ◽  
Hitoshi FUKUDA ◽  
Yohnosuke SHIMOMURA ◽  
...  

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