Introduction Thyroid hormone (TH) is an important regulator of cardiovascular functions. This becomes evident in patients with hyperthyroidism presenting with tachycardia and cardiac hypertrophy, while bradycardia is a characteristic of
Sogol Gachkar, Sebastian Nock, Cathleen Geissler, Rebecca Oelkrug, Kornelia Johann, Julia Resch, Awahan Rahman, Anders Arner, Henriette Kirchner and Jens Mittag
A S R Araujo, P Schenkel, A T Enzveiler, T R G Fernandes, W A Partata, S Llesuy, M F M Ribeiro, N Khaper, P K Singal and A Belló-Klein
stress in experimental hyperthyroidism, indicating that reactive oxygen species (ROS) may contribute to the progression to heart failure in this model ( Araujo et al . 2006 ). ROS are integral to the induction and maintenance of many signal transduction
Edwin J W Geven, Folkert Verkaar, Gert Flik and Peter H M Klaren
-treated fish (Fig. 1A ) and pituitary TSH β-subunit mRNA levels were 3.9-fold ( P <0.001) lower than in control animals (Fig. 1B ), which confirmed a successful induction of hyperthyroidism. The validation of our experimental hyperthyroid animal model is
W Grzesiuk, J Nieminuszczy, M Kruszewski, T Iwanienko, M Plazińska, M Bogdańska, E Bar-Andziak, L Królicki and E Grzesiuk
Introduction Changes in thyroid function are a common cause of endocrine illness. Overproduction of thyroid hormones, hyperthyroidism, can be due to Grave’s disease or autonomous thyroid nodule. In Poland, the frequency of both
A. J. Pickles, N. Peers, W. R. Robertson and A. Lambert
The microheterogeneity of pituitary thyroid-stimulating hormone (TSH) is dependent on variations in the hormone's carbohydrate moieties. In this study, changes in the pattern of heterogeneity have been assessed by chromatofocusing, which separates the isospecies on the basis of their isoelectric points (pI). Rats (n = 6 per group) were either untreated or rendered hypo- or hyperthyroid by including in the drinking water either propylthiouracil (0·05% for 8 weeks) or thyroxine (T4; 4 mg/l for 6 weeks) before they were killed at 16 weeks. On autopsy, serum TSH and total T4 were (means±s.e.m.): 2±0·3 μg TSH/l and 64±5 nmol T4/l (control); <1 μg TSH/1 and 133±6 nmol T4/l (hyperthyroid); 58±6 μg TSH/1 and 32±6 nmol T4/l (hypothyroid). The pituitaries were individually homogenized and the TSH isoforms separated by chromatofocusing over a pH range of 7–4. Fractions were assayed for TSH by radioimmunoassay. TSH from the control group was distributed into seven major peaks with pI values of (means ±s.e.m., n=6) 6·9±0·1, 6·6±0·1, 6·2±0·1, 5·8±0·1, 5·5±0·1, 5·2±0·1 and 4·8±0·1; 7±3% of the TSH had a pI of <40. Six peaks of TSH were conserved in the hypothyroid group (with pI values of 6·8±0·1, 6·5±0·1, 6·2±0·1, 5·8±0·1, 5·4±0·1 and 5·2±0·1), and 11±4% of the hormone had a pI of <40. In contrast to the other two groups, only one major peak (with a pI of 5·8±0·1) was detected in the pituitaries from the hyperthyroid group; 13 ± 5% of the TSH had a pI of <40. In the pH range of 5·5– 60, the per cent distribution of TSH was 58±15 (hyperthyroid) compared with 17 ± 3 (hypothyroid) and 22±3 (euthyroid). Above pH 6, only 25±13% of the TSH (hyperthyroid) was present compared with 46±5% (hypothyroid) and 45±5% (euthyroid). Below pH 5·5, the per cent distribution of TSH was 19±5 (hyperthyroid), 37±5 (hypothyroid) and 35±3 (euthyroid). In conclusion, both hyper- and hypothyroidism are associated with changes in the composition of pituitary TSH. This change was most marked in the hyperthyroid group, where there was a selective loss of several isoforms of TSH.
K Alexander Iwen, Rebecca Oelkrug and Georg Brabant
summarise the effects of (i) cold or heat exposure and (ii) fasting or fed states on metabolic processes. Finally, the disruption of these fine-tuned mechanisms by hyperthyroidism and hypothyroidism will be addressed. Components of thermoregulation
M R Thomas, J P Miell, A M Taylor, R J M Ross, J R Arnao, D E Jewitt and A M McGregor
Thyroid hormones are essential for the normal growth and development of many tissues. In the rat, hypothyroidism is associated with growth impairment, and hyperthyroidism with the development of a hypercatabolic state and skeletal muscle wasting but, paradoxically, cardiac hypertrophy. The mechanism by which thyroid hormone produces cardiac hypertrophy and myosin isoenzyme changes remains unclear. The role of IGF-I, an anabolic hormone with both paracrine and endocrine actions, in producing cardiac hypertrophy was investigated during this study in hyperthyroid, hypothyroid and control rats. A treated hypothyroid group was also included in order to assess the effect of acute normalization of thyroid function.
Body weight was significantly lower in the hyperthyroid (mean±s.e.m.; 535·5±24·9 g, P<0·05), hypothyroid (245·3±9·8 g, P<0·001) and treated hypothyroid (265·3±9·8 g, P<0·001) animals when compared with controls (618·5±28·6 g). Heart weight/body weight ratios were, however, significantly increased in the hyperthyroid (2·74 ± 0·11×10−3, P<0·01) and treated hypothyroid (2·87±0·07 ×10−3, P<0·001) animals when compared with controls (2·26±0·03 × 10−3). Serum IGF-I concentrations were similar in the control and hyperthyroid rats (0·91±0·07 vs 0·78±0·04 U/ml, P=0·26), but bioactivity was reduced by 70% in hyperthyroid serum, suggesting a circulating inhibitor of IGF. Serum IGF-I levels (0·12±0·03 U/ml, P<0·001) and bioactivity (0·12±0·04 U/ml, P<0·001) were significantly lower in the hypothyroid group. Liver IGF-I mRNA levels were not statistically different in the control and hyperthyroid animals, but were significantly reduced in the hypothyroid animals (P<0·05 vs control). Heart IGF-I mRNA levels were similar in the control and hypothyroid rats, but were significantly increased in the hyperthyroid and treated hypothyroid animals (increased by 32% in hyperthyroidism, P<0·05; increased by 57% in treated hypothyroidism, P<0·01). Cardiac IGF-I was significantly elevated in hyperthyroidism (0·16±0·01 U/mg heart tissue, P<0·01), was low in hypothyroidism (0·08±0·01 U/mg, P<0·01) and was normalized in the treated hypothyroid group (0·11 ± 0·01 U/mg vs control, 0·13±0·01 U/mg).
Low body mass during both hypothyroidism and hyperthyroidism is therefore associated with reduced systemic IGF bioactivity. In hypothyroidism there is a primary defect in the endocrine function of IGF-I, while in hyperthyroidism serum IGF bioactivity is reduced in the presence of normal endocrine production of this anabolic hormone. In contrast, the paracrine actions of IGF-I are increased in the heart during hyperthyroidism, and this hormone appears to play a part in the development of hyperthyroid cardiac hypertrophy.
Michelle Mohyi and Terry J Smith
immune tolerance to the thyrotropin receptor (TSHR) and the generation of activating antibodies against that protein. Further, hyperthyroidism, a central manifestation of GD, can be easily treated with commonly used and effective anti-thyroid medications
The journal apologises for an error that appeared in the article by Geven et al. in the December 2006 issue of the Journal of Molecular Endocrinology 37 , 443—452 , entitled ‘Experimental hyperthyroidism and central mediators of stress axis and
X Shen, QL Li, GA Brent and TC Friedman
Most pro-neuropeptides are processed by the prohormone convertases, PC1 and PC2. We previously reported that changes in thyroid status altered anterior pituitary PC1 mRNA and this regulation was due to triiodothyronine (T(3))-dependent interaction of thyroid hormone receptor (TR) with negative thyroid hormone response elements (nTREs) contained in a large region of the human PC1 promoter. In this study, we demonstrated that hypothyroidism stimulated, while hyperthyroidism suppressed, PC1 mRNA levels in rat hypothalamus and cerebral cortex, but not in hippocampus. In situ hybridization was used to confirm real-time PCR changes and localize the regulation within the hypothalamus and cortex. Using a human PC1 (hPC1) promoter construct (with and without deletions in two regions that each contain a negative TRE) transiently transfected into GH3 cells, we found that T(3) negatively regulated hPC1 promoter activity, and this regulation required both of these two regions. Electrophoretic mobility shift assays (EMSAs) using purified thyroid hormone receptor alpha1 (TRalpha1) and retinoid X receptor beta (RXRbeta) proteins demonstrated that RXR and TRalpha both bound the PC1 promoter. Addition of TRalpha1/RXRbeta to the wild-type PC1 probe demonstrated binding as both homodimers and a heterodimer. EMSAs with oligonucleotides containing deletion mutations of the putative nTREs demonstrated that the proximal nTRE binds more strongly to TR and RXR than the distal nTRE, but that both regions exhibit specific binding. We conclude that there are multiple novel TRE-like sequences in the hPC1 promoter and that these regions act in a unique manner to facilitate the negative effect of thyroid hormone on PC1.