THE EFFECT OF STREPTOZOTOCIN-INDUCED DIABETES ON THE PITUITARY-THYROID AXIS IN GOITROGEN-TREATED RATS

1977 ◽  
Vol 86 (1) ◽  
pp. 128-139 ◽  
Author(s):  
Isabel Pericás ◽  
Trinidad Jolín
Keyword(s):  
Body Weight ◽  
Thyroid Function ◽  
Growth Response ◽  
Thyroid Tissue ◽  
Diabetic Rats ◽  
Poor Growth ◽  
Pituitary Thyroid Axis ◽  
Tsh Secretion ◽  
Thyroid Axis ◽  
Intact Rats

ABSTRACT Studies of pituitary and thyroid function have been carried out in normal (intact) and diabetic Wistar rats. Diabetes was induced by a single streptozotocin injection (7 mg/100 g body weight). The animals were fed a low iodine diet (LID), and received a daily sc injection of either KClO4 (20 mg/100 g body weight) or propylthiouracil (PTU) (1.5 mg/100 g body weight) to induce hypothyroidism. Control groups received the same LID but supplemented with 0.8 μg I/g dry weight. In intact rats goitrogen-treatment induces an increase in thyroid weight and in plasma TSH concentration. However, the plasma TSH response to goitrogen-treatment in diabetics indicates that pituitary TSH secretion increases following a reduction in plasma PBI, but the response is less marked than in controls. The difference in plasma TSH between control and diabetic rats provides an explanation for the findings that diabetes diminishes the thyroid growth response to goitrogen-treatment. Moreover, in intact rats the low pituitary TSH content is a consequence of the increase in pituitary TSH secretion, while in the diabetics the low pituitary TSH content cannot be explained by an increase in TSH secretion. The effect of diabetes on the pituitary-thyroid axis cannot be attributed specifically to poor growth, because the changes in pituitary-thyroid function which are observed in the diabetic groups are not seen in intact rats with a growth rate similar to that of insulin deficient rats. Insulin administration to goitrogen-treated diabetic rats results in 1) an increase in the ability of the thyroid tissue to respond to its trophic hormone, 2) an increase in pituitary TSH secretion in response to the lowering of plasma PBI and, 3) an increase in thyroid growth response to goitrogen-treatment. Results are discussed in relation to the assumption that the lack of adequate insulin levels, or its metabolic defects, diminishes the full response of the thyroid to TSH, and affects the pituitary TSH secretion probably as a consequence of altered hypothalamic control of the pituitary function.

THYROID IODINE METABOLISM IN STREPTOZOTOCIN-DIABETIC RATS

1978 ◽  
Vol 88 (3) ◽  
pp. 506-516 ◽  
Author(s):  
Trinidad Jolín ◽  
Concepción González ◽  
Margarita González
Keyword(s):  
Body Weight ◽  
Thyroid Function ◽  
Diabetic Rats ◽  
Daily Injection ◽  
Iodide Uptake ◽  
Tsh Secretion ◽  
Male Wistar Rats ◽  
Streptozotocin Diabetic Rats ◽  
Isotopic Technique

ABSTRACT Experiments have been performed to assess the effect of diabetes on thyroid function in male Wistar rats. Diabetes was induced by a single streptozotocin injection. As compared to normals, the diabetic rats displayed: 1) decreased rate of stable iodine uptake by the gland, as measured with a double isotopic technique; 2) decreased in vitro iodide uptake by the thyroid; 3) decreased T/S [I-] ratio after acute treatment with propylthiouracil; and 4) alteration in the distribution of labelled iodoamino acids in the gland. Furthermore, diabetic rats maintained lower plasma TSH levels than normals, in spite of the fact that plasma PBI concentration was slightly but consistently lower in diabetic than in normals, and that the pituitary TSH content was not affected by the lack of normal insulin levels. Injections of TSH (5 U/100 g body weight/day) for 5 days, into diabetic rats caused a return of thyroid function toward normal. Insulin administration resulted in an increase of thyroid weight, an increase of thyroid function, and an increase of pituitary TSH secretion in diabetic rats after the daily injection of 1, 2 or 3 U/100 g body weight/day for 7 days. The decreased pituitary TSH secretion in diabetic rats might involve a disturbance in the feed-back relationship between the thyroid and the pituitary, although other mechanisms could be involved.

CHANGES OF THE HYPOTHALAMUS-PITUITARY-THYROID AXIS IN STREPTOZOTOCIN-DIABETIC RATS DURING ADAPTATION TO A LOW IODINE DIET

1978 ◽  
Vol 88 (4) ◽  
pp. 721-728 ◽  
Author(s):  
Eladio Montoya ◽  
Concepción González ◽  
Luis Lamas ◽  
Trinidad Jolín ◽  
Margarita González
Keyword(s):  
Iodine Content ◽  
Diabetic Rats ◽  
Control Group ◽  
Normal Ranges ◽  
Trh Stimulation ◽  
Pituitary Thyroid Axis ◽  
Tsh Secretion ◽  
Male Wistar Rats ◽  
Thyroid Axis ◽  
Streptozotocin Diabetic Rats

ABSTRACT Studies on the hypothalamus-pituitary-thyroid axis have been carried out in control and in diabetic male Wistar rats during adaptation to a 125I-labelled low iodine diet. Diabetes was induced by a single streptozotocin injection (7 mg/100 g body weight). Thyroid weight, thyroid 127I and 125I content, [125I]iodoamino acid distribution in thyroid digests, plasma PBI, plasma and pituitary TSH and hypothalamic TRH by radioimmunoassay were measured between 5 and 30 days after saline or streptozotocin injection, corresponding to 15 and 40 days after onset of the 125I-LID. As compared to controls, diabetic animals have smaller thyroids. The 125I and 127I in diabetic thyroids between 5 and 10 days was lower than in control glands; at longer intervals both 125I and 127I increased with time in diabetics, while no remarkable changes were seen in the control glands. Furthermore, the percentage of T3 and the MIT/DIT and T3/T4 ratios in thyroids of diabetic were lower than in the corresponding control group at all intervals. These results are compatible with a deficiency of TSH stimulation and/or with a high thyroidal iodine content. Compared to the controls, each group of diabetic rats presented a significantly lower plasma TSH concentration, in spite of the fact that its plasma PBI is more or similarly reduced in diabetic than in controls. Furthermore, the decreased pituitary TSH secretion in diabetic rats at early intervals is lower than in controls although the pituitary TSH and hypothalamic TRH remain within normal ranges. It is concluded that the decrease in pituitary TSH secretion may be the result of a reduction of pituitary TRH stimulation, secondary to a diminished secretion and/or synthesis of TRH by the hypothalamus.

scholarly journals Hypothyroidism reduces ObRb–STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action

2012 ◽  
Vol 215 (1) ◽  
pp. 129-135 ◽  
Author(s):  
Camila Calvino ◽  
Luana L Souza ◽  
Ricardo H Costa-e-Sousa ◽  
Norma A S Almeida ◽  
Isis H Trevenzoli ◽  
...  
Keyword(s):  
Body Weight ◽  
Pituitary Gland ◽  
Leptin Receptor ◽  
Single Injection ◽  
Stat3 Pathway ◽  
Pituitary Thyroid Axis ◽  
Tsh Secretion ◽  
Thyroid Axis ◽  
Stat3 Signalling ◽  
Phosphorylated Stat3

Leptin has been shown to regulate the hypothalamus–pituitary–thyroid axis, acting primarily through the STAT3 pathway triggered through the binding of leptin to the long-chain isoform of the leptin receptor, ObRb. We previously demonstrated that although hyperthyroid rats presented leptin effects on TSH secretion, those effects were abolished in hypothyroid rats. We addressed the hypothesis that changes in the STAT3 pathway might explain the lack of TSH response to leptin in hypothyroidism by evaluating the protein content of components of leptin signalling via the STAT3 pathway in the hypothalamus and pituitary of hypothyroid (0.03% methimazole in the drinking water/21 days) and hyperthyroid (thyroxine 5 μg/100 g body weight /5 days) rats. Hypothyroid rats exhibited decreased ObRb and phosphorylated STAT3 (pSTAT3) protein in the hypothalamus, and in the pituitary gland they exhibited decreased ObRb, total STAT3, pSTAT3 and SOCS3 (P<0.05). Except for a modest decrease in pituitary STAT3, no other alterations were observed in hyperthyroid rats. Moreover, unlike euthyroid rats, the hypothyroid rats did not exhibit a reduction in food ingestion after a single injection of leptin (0.5 mg/kg body weight). Therefore, hypothyroidism decreased ObRb–STAT3 signalling in the hypothalamus and pituitary gland, which likely contributes to the loss of leptin action on food intake and TSH secretion, as previously observed in hypothyroid rats.

scholarly journals Chronothyroidology: Chronobiological Aspects in Thyroid Function and Diseases

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 426
Author(s):  
Giuseppe Bellastella ◽  
Maria Ida Maiorino ◽  
Lorenzo Scappaticcio ◽  
Annamaria De Bellis ◽  
Silvia Mercadante ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Biological Rhythms ◽  
Cellular Level ◽  
Scientific Discipline ◽  
Biological Phenomena ◽  
Pituitary Thyroid Axis ◽  
Circadian Organization ◽  
Thyroid Axis ◽  
Central Clock ◽  
Thyroid Dysfunctions

Chronobiology is the scientific discipline which considers biological phenomena in relation to time, which assumes itself biological identity. Many physiological processes are cyclically regulated by intrinsic clocks and many pathological events show a circadian time-related occurrence. Even the pituitary–thyroid axis is under the control of a central clock, and the hormones of the pituitary–thyroid axis exhibit circadian, ultradian and circannual rhythmicity. This review, after describing briefly the essential principles of chronobiology, will be focused on the results of personal experiences and of other studies on this issue, paying particular attention to those regarding the thyroid implications, appearing in the literature as reviews, metanalyses, original and observational studies until 28 February 2021 and acquired from two databases (Scopus and PubMed). The first input to biological rhythms is given by a central clock located in the suprachiasmatic nucleus (SCN), which dictates the timing from its hypothalamic site to satellite clocks that contribute in a hierarchical way to regulate the physiological rhythmicity. Disruption of the rhythmic organization can favor the onset of important disorders, including thyroid diseases. Several studies on the interrelationship between thyroid function and circadian rhythmicity demonstrated that thyroid dysfunctions may affect negatively circadian organization, disrupting TSH rhythm. Conversely, alterations of clock machinery may cause important perturbations at the cellular level, which may favor thyroid dysfunctions and also cancer.

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 The Hypothalamic-Pituitary-Thyroid Axis in Cushing Syndrome before and after Curative Surgery

2020 ◽  
Author(s):  
Skand Shekhar ◽  
Raven McGlotten ◽  
Sunyoung Auh ◽  
Kristina I Rother ◽  
Lynnette K Nieman
Keyword(s):  
Thyroid Function ◽  
Cushing’S Syndrome ◽  
Cushing Syndrome ◽  
Cushing's Syndrome ◽  
Curative Surgery ◽  
Central Hypothyroidism ◽  
Duration Of Symptoms ◽  
Before And After ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis

Abstract Background We do not fully understand how hypercortisolism causes central hypothyroidism or what factors influence recovery of the hypothalamic-pituitary-thyroid axis. We evaluated thyroid function during and after cure of Cushing’s syndrome (CS). Methods We performed a retrospective cohort study of adult patients with CS seen from 2005 – 2018 (cohort 1, c1, n=68) or 1985 – 1994 (cohort 2, c2, n=55) at a clinical research center. Urine (UFC) and diurnal serum cortisol (F: ~8AM and ~midnight (PM)), morning triiodothyronine (T3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) (c1) or hourly TSH from 1500-1900h (day) and 2400-04000h (night) (c2), were measured before and after curative surgery. Results While hypercortisolemic, 53% of c1 had central hypothyroidism (low/low normal fT4 + unelevated TSH). Of those followed long-term, 31% and 44% had initially subnormal FT4 and T3, respectively, which normalized 6—12 months after cure. Hypogonadism was more frequent in hypothyroid (69%) compared to euthyroid (13%) patients. Duration of symptoms, AM and PM F, ACTH, and UFC were inversely related to TSH, FT4 and/or T3 levels (r -0.24 to -0.52, P &lt;0.0001 to 0.02). In c2, the nocturnal surge of TSH (mIU/L) was subnormal before (day 1.00±0.04 vs night 1.08±0.05, p=0.3) and normal at a mean of 8 months after cure (day 1.30±0.14 vs night 2.17±0.27, p=0.01). UFC &gt;1000 μg /day was an independent adverse prognostic marker of time to thyroid hormone recovery. Conclusions Abnormal thyroid function, likely mediated by subnormal nocturnal TSH, is prevalent in Cushing’s syndrome and is reversible after cure.

scholarly journals The role of leptin in the regulation of TSH secretion in the fed state: in vivo and in vitro studies

2002 ◽  
Vol 174 (1) ◽  
pp. 121-125 ◽  
Author(s):  
TM Ortiga-Carvalho ◽  
KJ Oliveira ◽  
BA Soares ◽  
CC Pazos-Moura
Keyword(s):  
Fold Increase ◽  
Adult Rats ◽  
Fed State ◽  
Rat Pituitary ◽  
Pituitary Thyroid Axis ◽  
Tsh Secretion ◽  
Thyroid Axis

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.

scholarly journals ADGRA1 negatively regulates energy expenditure and thermogenesis through both sympathetic nervous system and hypothalamus–pituitary–thyroid axis in male mice

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Xiao-Hong Zhang ◽  
Ling-Yun Tang ◽  
Xi-Yi Wang ◽  
Chun-Ling Shen ◽  
Wen-Feng Xiong ◽  
...  
Keyword(s):  
Nervous System ◽  
Body Weight ◽  
Adipose Tissue ◽  
Sympathetic Nervous System ◽  
Male Mice ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Sympathetic Nervous ◽  
G Protein Coupled ◽  
Mutant Male

AbstractAdhesion G protein-coupled receptor A1 (ADGRA1, also known as GPR123) belongs to the G protein-coupled receptors (GPCRs) family and is well conserved in the vertebrate lineage. However, the structure of ADGRA1 is unique and its physiological function remains unknown. Previous studies have shown that Adgra1 is predominantly expressed in the central nervous system (CNS), indicating its important role in the transduction of neural signals. The aim of this study is to investigate the central function of Adgra1 in vivo and clarify its physiological significance by establishing an Adgra1-deficient mouse (Adgra1−/−) model. The results show that Adgra1−/− male mice exhibit decreased body weight with normal food intake and locomotion, shrinkage of body mass, increased lipolysis, and hypermetabolic activity. Meanwhile, mutant male mice present elevated core temperature coupled with resistance to hypothermia upon cold stimulus. Further studies show that tyrosine hydroxylase (TH) and β3-adrenergic receptor (β3-AR), indicators of sympathetic nerve excitability, are activated as well as their downstream molecules including uncoupling protein 1 (UCP1), coactivator 1 alpha (PGC1-α) in brown adipose tissue (BAT), and hormone-sensitive lipase (HSL) in white adipose tissue (WAT). In addition, mutant male mice have higher levels of serum T3, T4, accompanied by increased mRNAs of hypothalamus–pituitary–thyroid axis. Finally, Adgra1−/− male mice present abnormal activation of PI3K/AKT/GSK3β and MEK/ERK pathways in hypothalamus. Overexpression of ADGRA1 in Neuro2A cell line appears to suppress these two signaling pathways. In contrast, Adgra1−/− female mice show comparable body weight along with normal metabolic process to their sex-matched controls. Collectively, ADGRA1 is a negative regulator of sympathetic nervous system (SNS) and hypothalamus–pituitary–thyroid axis by regulating PI3K/AKT/GSK3β and MEK/ERK pathways in hypothalamus of male mice, suggesting an important role of ADGRA1 in maintaining metabolic homeostasis including energy expenditure and thermogenic balance.

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