Possible Role Of Thyroid Hormones Research Articles

Effects of Thyroid Hormone on Tissue Hypoxia: Relevance to Sepsis Therapy.

Tissue hypoxia occurs in various conditions such as myocardial or brain ischemia and infarction, sepsis, and trauma, and induces cellular damage and tissue remodeling with recapitulation of fetal-like reprogramming, which eventually results in organ failure. Analogies seem to exist between the damaged hypoxic and developing organs, indicating that a regulatory network which drives embryonic organ development may control aspects of heart (or tissue) repair. In this context, thyroid hormone (TH), which is a critical regulator of organ maturation, physiologic angiogenesis, and mitochondrial biogenesis during fetal development, may be of important physiological relevance upon stress (hypoxia)-induced fetal reprogramming. TH signaling has been implicated in hypoxic tissue remodeling after myocardial infarction and T3 prevents remodeling of the postinfarcted heart. Similarly, preliminary experimental evidence suggests that T3 can prevent early tissue hypoxia during sepsis with important physiological consequences. Thus, based on common pathways between different paradigms, we propose a possible role of TH in tissue hypoxia after sepsis with the potential to reduce secondary organ failure.

Effects of Thyroid Hormones and their Metabolites on Learning and Memory in Normal and Pathological Conditions.

Classical thyroid hormones have an established necessary role in the normal development of the central nervous system, and they have been recently considered as decisive factors influencing cognitive functions in the adult brain and involved in the development of Alzheimer's disease. The picture summarizing thyroid hormone effects on the adult brain, however, does not only include classical thyroid hormones but also the products of their peripheral metabolism. These latter have been considered as inactive breakdown products for long but recently were proved to produce significant biological effects. In this review article we presented recent evidence supporting the hypothesis that thyroid hormones exert a neuroprotective effect in the brain areas involved in learning and memory. Moreover, we summarized the evidence that suggests that non-classical thyroid hormones produce significant neurological effects in the adult brain. We also discussed the possible role of thyroid hormones in the cognitive impairment, typical of Alzheimer's disease. A comprehensive review of the literature based on the current knowledge of the effects of classical and nonclassical thyroid hormones on the adult brain and their role in Alzheimer's disease was performed. The available literature suggests that both classical and non-classical thyroid hormones act as neuroprotective agents in the brain areas related to learning and memory. Their role in these areas supports the idea that they may be involved in the development of Alzheimer's disease. Thyroid hormones produce significant neurological effects, act as neuroprotective agents and might be considered as future diagnostic and therapeutic tools for Alzheimer's disease.

Assessment of thyroid hormones status and some adipocytokines among Egyptian obese children

Aim: Childhood obesity is one of the most serious public health problems facing the developed and increasingly, the developing world. In this study, we aimed to investigate the possible role of thyroid hormones and some adipokines in childhood obesity. Materials & methods: A total of 80 children were enrolled; 50 obese children and 30 non-obese of matched age and sex. Clinical, demographic characteristics and lipid profile levels were monitored. Plasma levels of thyroid hormones, leptin, IL-1α and TNF-α were measured in these subjects. Results: Dyslipidemia was evident in obese children relative to normal ones. Obese children exhibited a significant reduction in TSH and free- T4 levels. There was an increment in both leptin and IL-1α levels of obese children, however, their TNF-α level were significantly decreased. Conclusion: Alterations in thyroid hormones status, leptin, IL-1α and TNF-α are associated with obesity in Egyptian children.

The Pattern of Expression and Role of Triiodothyronine (T3) Receptors and Type I 5′-Deiodinase in Breast Carcinomas, Benign Breast Diseases, Lactational Change, and Normal Breast Epithelium

: To study the pattern of expression of triiodothyronine (T3) receptors and type I 5'-deiodinase in various breast pathologies comparing malignant and nonmalignant epithelia that include lactational change. A retrospective study was performed on formalin-fixed, paraffin-embedded archival material from 146 cases of carcinomas, normal breast tissue, breast tissue showing lactational change, and benign breast lesions. Archive tissue blocks were selected and sections were cut for immunohistochemistry to study the expression of thyroid hormone receptor α-1 (THR-α1) in the cytoplasm and nuclei of cells in tissues under study. Thick sections were cut for type I 5'-deiodinase evaluation using reverse transcriptional PCR.THR-α1 showed no nuclear expression in the carcinoma group. Combined nuclear and cytoplasmic expression was seen in 47.6%, 63.4%, 64.3%, and 58.3% in the benign, fibrocystic, fibroadenoma, and lactational change groups, respectively, compared with only 17.4% of cases in the carcinoma group. This suggests deregulation of the thyroid hormone in breast cancer. Theories for the possible role of thyroid hormone in the pathogenesis of breast cancer are discussed.Type I 5'-deiodinase was not shown to be differentially expressed in malignant versus nonmalignant groups. Our study revealed substantial reduction in the protein expression profile of THRs in malignant versus nonmalignant mammary epithelium suggesting a possible role in breast cancer development. The presence of THRs in mammary epithelium seems to be protective against the development of breast cancer. This could serve as a potential prognostic and therapeutic target for breast cancer.

Thyroid hormone transporters during testicular development in rodents

Introduction: Chronic dietary induced perinatal hypothyroidism results in a transient delay in Leydig cell and prolonged Sertoli cell proliferation in neonatal rat testes, hence the start of complete spermatogenesis is altered. In the present study we have investigated the possible role of thyroid hormone (TH) transporters and receptors (TR) in relation to the delayed onset of spermatogenesis.

Lake Tana large barbs diversity: Developmental and hormonal bases

Helerochronies caused by changes in the hormonal status are proposed to play a major role in the diversification of the Lake Tana barbs of Labeobarbus (=Barbus) genus (Dgebuadze and Mina, 2008). To test this hypothesis, we (i) compared temporal patterns of cranial development in L. intermedius, likely ancestral for Tana species flock, and L. brevicephalus and L. megastoma proposed to be paedomoiphic and peramoiphic, respectively; (ii) studied the role of thyroid hormone (TH) in the regulation of L. intermedius development; (iii) evaluated the effect of TH changes on the definitive morphology, and (iv) evaluated the possible role of TH in diversification of Tana barbs. Skull development was found to be heterochronicaily changed in L. brevicephalus and L. megastoma as compared to L. intermedius; revealed heteroclironies may account for differences in skull proportions distinguishing these barbs, TH was shown to play a major role in the regulation of ontogeny. Changes in TH level cause heterochronies in the development of a skull, axial skeleton, fins and fin girdles, squamation, and dentition. Heteroclironies were shown to influence adult morphology of these structures. These findings support the hypothesis of the involvement of developmental and hormonal factors in the diversification of the Lake Tana large barbs.

Thyroid hormone: the modulator of erectile function in the rabbit.

The possible role of thyroid hormones in the Nitric Oxide (NO)-mediated response to sexual stimulation, and on prostaglandin E1 (PGE1) and Sildenafil in the treatment of erectile dysfunction was investigated using the corpus cavernosum of the New Zealand rabbit animal model. The parameters studied were penile erection monitored as contractile force of the erectile tissue, sperm count and motility; in parallel with the haematocrit, red cell count or rheology, Heart Rate (HR), Mean Arterial Pressure (MAP), Thyroid Stimulating Hormones (TSH) and Thyroxine levels. Hypothyroidism or thyroidectomy was found to cause depletion of Endothelium Derived Relaxant Factor (EDRF) thereby causing very feeble contraction of the cavernosum muscle, in both prostaglandin E1 (PGE1) and sildenafil, oligospermia and less than 45 % motile sperms. Thyroxine treatment produced contraction proportionate to the concentrations of PGE1 and Sildenafil; providing evidence that the erectogenic actions of both PGE1 and Sildenafil are possible only in the presence of adequate thyroid hormone level.

Hypothyroidism is associated with increased myostatin expression in rats

Besides its key role in the regulation of muscle growth during development, myostatin also appears to be involved in muscle homeostasis in adults, and its expression is upregulated during muscle atrophy. Since muscle physiology is greatly influenced by thyroid status, and the myostatin promoter region contains several putative thyroid hormone response elements, in the present study we examined the possible role of thyroid hormones in the regulation of myostatin gene expression. Adult male rats were made either hypothyroid or hyperthyroid by means of administration of 0.1% amino- triazole (AMT) in drinking water for 4 weeks, or daily injections of Levo-T4 (L-T4) (100 microg/rat) for 3 weeks, respectively. At the end of the treatment period, both myostatin mRNA and protein content were increased in AMT-treated rats in relation to control rats. In contrast, no changes in myostatin mRNA levels were detected in L-T4-treated rats. The role of thyroid hormones in the regulation of myostatin expression was also investigated in C2C12 cells in vitro. Treatment of C2C12 cells with thyroid hormones stimulated their differentiation into multinucleated myotubes, but did not induce any change in myostatin mRNA abundance. In all, our findings demonstrate that myostatin expression is increased in hypothyroid rats, thus supporting a possible role for this factor in the pathogenesis of the muscle loss that may occur in hypothyroidism.

Thyroid hormone is a critical determinant of myocardial performance in patients with heart failure: potential therapeutic implications

Previous experimental studies have provided evidence showing that changes in thyroid hormone signaling correspond to alterations in myocardial function in animal models of heart failure. The present study further explores whether thyroid hormone alterations are correlated with the functional status of the myocardium in patients with heart failure. In this study, 37 patients with mean ejection fraction (EF%) of 26.2 (8.2) were included. Myocardial performance was assessed by echocardiography and cardiopulmonary exercise testing. Total tri-iodothyronine (T3), thyroxine, and TSH levels were measured in plasma. Total T3 was strongly correlated with VO2max (r = 0.78, P = 2 x 10(-8)). Furthermore, multivariate analysis revealed that total T3 was an independent predictor of VO2max (P = 0.000 005). A weaker but significant correlation was also found between total T3 and EF% (r = 0.56, P = 0.0004), systolic (r = 0.43, P = 0.009) and diastolic (r = 0.46, P = 0.004) blood pressure. changes in thyroid hormone were closely correlated to myocardial functional status in patients with heart failure. These data probably indicate a possible role of thyroid hormone in the pathophysiology of heart failure and confirm previous experimental reports.

Dependence of calcium on thyroid hormone for the regulation of cellular functions.

Recently, the thyroid hormone has been shown to cause increase in Ca2+ concentration by mobilizing intracellular Ca2+. The mobilization of intracellular Ca2+ in the absence of transmembrane Ca2+ influx has been accepted as evidence for a cell-surface Ca2+- receptor. The possible role of thyroid hormone in the regulation of cellular functions by Ca2+-channel was investigated using parameters proven to indispensably involve Ca2+: Bleeding and clotting times and rat uterine muscle activity in Ca2+-free Tyrode's solution. Adult female Wistar rats divided into four groups, namely; (i) Control, (ii) Thyroidectomized, (iii) Throidectomized-treated with thyroxine and (iv) Thyroxine-treated; were fed on rat chow. While groups i and ii were allowed access to tap water ad libitum for 60 days, groups iii and iv received tyroxine (10mg/kg body weight) every alternate day and tap water ad libitum for 60 days. All groups were kept in an air-conditioned room till they were euthanized. The results showed that thyroxine elicited biphasic contraction in Ca2+ - depletion and potentiated uterine contraction during Ca2+- loading (P<0.001). Inhibition of contractions in thyroidectomy, showed dependency of Ca2+ on thyroid hormones for the regulation of cellular functions.

Maternal thyroid hormones early in pregnancy and fetal brain development

During the last few decades our understanding of the possible role of thyroid hormones during brain development has increased and contributed to resolve previously discordant hypotheses, although much remains to be clarified. Thyroid hormones of maternal origin are present in the fetal compartment, despite the very efficient uterine-placental ‘barrier’, necessary to avoid potentially toxic concentrations of free T4 and T3 from reaching fetal tissues before they are required for development. T3 remains low throughout pregnancy, whereas FT4 in fetal fluids increases rapidly to adult levels, and is determined by the maternal availability of T4. It is present in embryonic fluids 4 weeks after conception, with FT4 steadily increasing to biologically relevant values. T3, generated from T4 in the cerebral cortex, reaches adult values by mid-gestation and is partly bound to specific nuclear receptor isoforms. Iodothyronine deioidinases are important for the spatial and temporal regulation of T3 bioavailability, tailored to the differing and changing requirements of thyroid hormone-sensitive genes in different brain structures, but other regulatory mechanism(s) are likely to be involved. Maternal transfer constitutes a major fraction of fetal serum T4, even after onset of fetal thyroid secretion, and continues to have an important protective role in fetal neurodevelopment until birth. Prompt treatment of maternal hypothyroidism, identified by increased TSH, is being advocated to mitigate a negative effect on the woman and her child. However, even a moderate transient period of maternal hypothyroxinemia at the beginning of rat neurogenesis disrupts neuronal migration into cortical layers. These findings reinforce the epidemiological evidence that early maternal hypothyroxinemia—when neuronal migratory waves are starting—is potentially damaging for the child. Detection of an inappropiate first trimester FT4 surge that may not result in increased TSH, may be crucial for the prevention of learning disabilities in a significant number of unborn children.

Maternal thyroid hormones early in pregnancy and fetal brain development.

During the last few decades our understanding of the possible role of thyroid hormones during brain development has increased and contributed to resolve previously discordant hypotheses, although much remains to be clarified. Thyroid hormones of maternal origin are present in the fetal compartment, despite the very efficient uterine-placental 'barrier', necessary to avoid potentially toxic concentrations of free T4 and T3 from reaching fetal tissues before they are required for development. T3 remains low throughout pregnancy, whereas FT4 in fetal fluids increases rapidly to adult levels, and is determined by the maternal availability of T4. It is present in embryonic fluids 4 weeks after conception, with FT4 steadily increasing to biologically relevant values. T3, generated from T4 in the cerebral cortex, reaches adult values by mid-gestation and is partly bound to specific nuclear receptor isoforms. Iodothyronine deioidinases are important for the spatial and temporal regulation of T3 bioavailability, tailored to the differing and changing requirements of thyroid hormone-sensitive genes in different brain structures, but other regulatory mechanism(s) are likely to be involved. Maternal transfer constitutes a major fraction of fetal serum T4, even after onset of fetal thyroid secretion, and continues to have an important protective role in fetal neurodevelopment until birth. Prompt treatment of maternal hypothyroidism, identified by increased TSH, is being advocated to mitigate a negative effect on the woman and her child. However, even a moderate transient period of maternal hypothyroxinemia at the beginning of rat neurogenesis disrupts neuronal migration into cortical layers. These findings reinforce the epidemiological evidence that early maternal hypothyroxinemia-when neuronal migratory waves are starting-is potentially damaging for the child. Detection of an inappropiate first trimester FT4 surge that may not result in increased TSH, may be crucial for the prevention of learning disabilities in a significant number of unborn children.

Evaluation of serum leptin levels and thyroid function in morbidly obese patients treated with bariatric surgery.

Biliopancreatic diversion (BPD), a gastrectomy with a long ROUX en Y reconstruction, reduces intestinal absorption by delaying the mixing of food and biliopancreatic juices, and induces persistent weight loss in obese patients unresponsive to medical treatments. The levels of leptin (a plasma protein synthesised in human adipose tissue) are increased in obese subjects and significantly decrease after a major weight loss. A possible role of thyroid hormones in regulating adipose tissue metabolism in humans has been proposed, but it is not universally accepted and the relationship between thyroid function and leptin levels has not yet been clearly defined. We studied serum leptin, TSH, fT4 and fT3 levels in 38 obese patients (26 women and 12 men), before and 12 months after BPD. There was a significant post-surgical decrease in BMI and circulating leptin levels in all of the treated subjects, but thyroid function did not seem to be affected (TSH and fT4 levels were unchanged). However, fT3 levels significantly decreased after surgery. Our data suggest that BPD-induced malabsorption has no direct effect on thyroid function, but possibly reduces the peripheral conversion of thyroxine to T3. Further studies seem to be necessary to clarify the clinical relevance of these observations.

Effects of Thyroid Hormones on Cardiac Structure: A Tissue Characterization Study in Patients with Thyroid Disorders Before and After Treatment

Experimental evidence suggests an involvement of thyroid hormones in myocardial nonmyocyte component growth. We evaluated the possible role of thyroid hormones in myocardial remodeling by ultrasonic tissue characterization (videodensitometry) in 8 hyperthyroid patients, in 10 hypothyroid patients, and in 2 patients with thyroid hormone resistance syndrome (RTH), before, 60, and 120 days after treatment (T0, T60, T120), and in 10 age-matched euthyroids. According to a previously described procedure, the derived collagen volume fraction (dCVF%, an echocardiographic index estimating the collagen content) was predicted from the pixel-level frequency distribution width (broadband, Bb) of the selected echocardiographic images. Thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were assessed by immunometric method. QT interval dispersion (QTd) on basal electrocardiogram was measured as a marker of dyshomogeneous ventricular repolarization. At T0, Bb and dCVF% were normal in hyperthyroid and euthyroid patients, and slightly increased in RTH patients, whereas significantly higher values were found in hypothyroids. At T60, a significant reduction in Bb was observed in hypothyroids, with nearly normal dCVF% values. This trend was confirmed at T120 with complete normalization of echoreflectivity. No echoreflectivity changes were observed in hyperthyroid and RTH patients during treatment. QTd was significantly increased in hypothyroids at T0, while no significant differences were found among groups at T60 and T120. Because the different videodeonsitometric myocardial properties observed in hypothyroid versus hyperthyroid patients correspond to an increase of dCVF%, this study suggests that thyroid hormones exert an inhibitory effect on myocardial collagen synthesis in humans.

Negative regulation of the antimetastatic gene Nm23-H1 by thyroid hormone receptors.

Metastasis of various malignant cells is inversely related to the abundance of the Nm23-H1 protein. The possible role of thyroid hormones in tumor metastasis has now been investigated by examining the effect of T3 on the expression of the Nm23-H1 gene. Human hepatoma HepG2 cells, in which endogenous thyroid hormone receptor subtype alpha1 (TRalpha1) is expressed at a low level, were stably transfected, either with expression plasmids encoding wild-type TRalpha1 or a dominant negative mutant of TRalpha1, or with the empty vector (yielding HepG2-Wt, HepG2-Mt, and HepG2-Neo cells, respectively). Immunoblot analysis revealed that exposure of HepG2-Wt and HepG2-Neo cells, but not HepG2-Mt cells, to T3-induced time-dependent decreases in the abundance of Nm23-H1 messenger RNA and protein, with the extent of these effects correlating with the level of expression of TRalpha1. An in vitro assay also revealed that T3 induced a marked increase in the invasive activity of HepG2-Wt cells; it induced a smaller increase in that of HepG2-Neo cells but had no effect on that of HepG2-Mt cells. Finally, the promoter region of Nm23-H1 spanning nucleotides -471 to -437 (relative to the transcriptional initiation site) inhibited the expression of a downstream reporter gene, in a T3-dependent manner, in COS-1 cells also transfected with an expression plasmid encoding TRalpha1 or TRbeta1. The DNA binding domain of TRbeta1 was required for this inhibitory effect. These results indicate that T3, acting through TRs, inhibits transcription of Nm23-H1, and that this effect is mediated by a negative regulatory element in the promoter region of the gene. Thus, it is possible that T3 promotes tumor metastasis by inducing down-regulation of Nm23-H1 expression.

Effects of Thyroid Hormone on Serum Insulin-Like Growth Factor Binding Proteins(IGFBPs) and IGFBP-2 mRNA Expression in Chickens.

We examined serum IGF binding proteins (IGFBPs) and tissue (liver, kidney and brain) IGFBP-2 mRNA in 5-weeks-old cockerels with different thyroidal status to elucidate a possible role of thyroid hormone on IGFBPs in the chicken. Assay for serum IGFBPs by Western ligand blot detected three IGFBPs having molecular masses of 30, 36 and 41 kDa. The 125I-IGF-I bindings to these IGFBPs were significantly decreased in propylthiouracil (PTU) induced hypothyroid cockerels, and restored to euthyroid control levels by thyroxine (T4) supplement. T4 supplement to euthyroid birds had no significant influence on 125I-IGF-I binding to IGFBPs. The expression of IGFBP-2 mRNA in the liver was significantly reduced in hypothyroidism and restored to normal level by T4 replacement, whereas T4, injected to intact birds, failed to affect hepatic IGFBP-2 mRNA expression. In contrast, the expression of IGFBP-2 mRNA in the kidney was increased in hypothyroid birds and decreased both in T4-treated intact and hypothyroid birds. In the brain, IGFBP-2 mRNA level was not influenced by the changes in thyroidal status. IGFBP-2 mRNA was detected in all tissues examined, with varying degree. The expression was higher in the testis, gizzard, brain, eye and bursa of fabricius, followed by kidney and digestive organs. In the liver, the expression was very low compared with other tissues.

Impact of suppression of thyroxine on folate status during acute antidepressant therapy

Antidepressant response is associated with a rise in red cell folate (RCF) and a reduction in thyroxine (T4). Since T4 levels may directly influence folate status, it is possible that the increase in folate with recovery results from the decline in T4. To examine the possible role of thyroid hormones in the observed change in folate status during antidepressant therapy, T4, tri-iodothyronine (T3) or placebo was given in a double-blind fashion to 25 depressed subjects at the initiation of standard antidepressant treatment. Folate levels and mood [using the Hamilton Rating Scale for Depression (HAMD), Montgomery-Åsberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI)] were measured at baseline and following 4 weeks of therapy. Using MANOVA for repeated measures, there was a significant interaction between response status and time for vitamin and hormone levels. Univariate analysis confirmed that response was associated with a significant change in red cell folate, but not a significant change in T4 or T3. The mean change in RCF across the 4-week trial was significantly greater in the 14 responders than the 11 non-responders. Change in RCF, and not change in T4 or T3, was significantly correlated with change in HAMD and contributed significantly to the variance in change in HAMD. These results suggest that change in RCF is closely tied to response to antidepressant treatment, and this effect is not inhibited by exogenous administration of thyroid hormones or the changes in T4 that the exogenous hormones produce. These findings support the possible role of folate, independent of thyroid function, in the modulation of mood.

Tissue-specific regulation of medium-chain acyl-CoA dehydrogenase gene by thyroid hormones in the developing rat

During development, gene expression of medium-chain acyl-CoA dehydrogenase (MCAD), a nuclear-encoded mitochondrial enzyme that catalyses the first step of medium-chain fatty acid beta-oxidation, is highly regulated in tissues in accordance with fatty acid utilization, but the factors involved in this regulation are largely unknown. To investigate a possible role of thyroid hormones, rat pups were made hypothyroid by the administration of propylthiouracyl to the mother from day 12 of gestation, and their kidneys, heart and liver were removed on postnatal day 16 to determine MCAD mRNA abundance, protein level and enzyme activity. Similar experiments were run in 3,3',5-tri-iodothyronine (T3)-replaced hypothyroid (1 microg of T3/100 g body weight from postnatal day 5 to 15) and euthyroid pups. Hypothyroidism led to an increase in MCAD mRNA abundance in kidney and a decrease in abundance in heart, but had no effect in liver. The protein levels and enzyme activity were lowered in hypothyroid heart and kidney, suggesting that hypothyroidism affects post-transcriptional steps of gene expression in the kidney. All the effects of hypothyroidism were completely reversed in both heart and kidney by T3 replacement. Injection of a single T3 dose into 16-day-old euthyroid rats also led to tissue-specific changes in mRNA abundance. Nuclear run-on assays performed from hypothyroid and hypothyroid plus T3 rats showed that T3 stimulates MCAD gene transcription in heart and represses it in the kidney. These results indicate that the postnatal rise in circulating T3 is essential to the developmental regulation of the MCAD gene in vivo.

Involvement of thyroid hormones in the expression of MHC class I antigens during ontogeny in Xenopus.

The major histocompatibility complex (MHC) is a cluster of genes encoding products central to all major functions of the vertebrate immune system. Evidence for an MHC can be found in all vertebrate groups that have been examined except the jawless fishes. Expression of MHC class I and class II antigens early in ontogeny is critically important for development of T lymphocytes capable of discriminating self from nonself. Because of this essential role in T-cell development, the ontogeny of MHC expression in the South African clawed frog, Xenopus laevis, was studied. Previous studies of MHC class I expression in Xenopus laevis suggested that class I antigens are virtually absent from tadpole tissues until climax of metamorphosis. We therefore examined the possible role of thyroid hormones (TH) in the induction of class I. By flow cytometry, a small amount of class I expression was detectable on splenocytes and erythrocytes in untreated frogs at prometamorphic stages 55-58, and the amount increased significantly at the conclusion of metamorphic climax. Thus, metamorphosis is associated with increased intensity of class I expression. Neither inhibition nor acceleration of metamorphosis altered the timing of onset of class I expression. However, inhibition of metamorphosis prevented the increase in class I expression characteristic of adult cell populations. Because expression was not accelerated in TH-treated frogs or delayed in metamorphosis-inhibited frogs, it is unlikely that TH are the direct developmental cues that induce expression, although they seem to be required for the upregulation of class I expression occurring at metamorphosis. Differences in the pattern of expression in different subpopulations of cells suggest a complex pattern of regulation of expression of class I antigens during ontogeny.

Low resting metabolic rate in subjects predisposed to obesity: a role for thyroid status

A low resting metabolic rate (RMR) for a given body composition has been identified as a risk factor for weight gain and obesity, and has also been reported in formerly obese individuals with the genetic predisposition for obesity. The possible role of thyroid hormone in low RMR was studied in a large sample of postobese women. RMR was measured by indirect calorimetry in 28 weight-stable postobese women with a family history of obesity (PO group) and in a control group of 28 nonobese women closely matched for age, fat mass, and fat-free mass. RMR was 8% lower in the PO than in the control group [[symbol: see text]; 95% Cl:5856 (5520, 6214) compared with 6408 kJ/d (6096, 6768 kJ/d), P < 0.02], and the group difference remained unchanged after fat-free mass and fat mass were adjusted for (552 kJ/d, P < 0.015). The PO group had lower plasma free triiodothyronine [2.4 (1.9, 3.0) compared with 3.4 pmol/L (2.9, 3.9 pmol/L), P < 0.01], whereas plasma androstenedione only tended to be lower in the PO than in the control group. Adjustment for differences in androstenedione did not reduce the difference in RMR, whereas adjustment for differences in plasma free triiodothyronine eliminated the group difference (96 kJ/d, P = 0.59). The present study shows that RMR for a given body composition is lower among postobese than among matched never-obese control subjects. Statistically, the lower plasma free triiodothyronine concentrations of the postobese subjects could explain their lower RMRs, but it remains to be established whether these findings are causally related.