Upregulation of Slc39a10 gene expression in response to thyroid hormones in intestine and kidney

A novel zinc transporter has been purified and cloned from rat renal brush border membrane. This transporter was designated as Zip10 encoded by Slc39a10 gene and characterized as zinc importer. Present study documents the impact of thyroid hormones on the expression of Zip10 encoded by Slc39a10 gene in rat model of hypo and hyperthyroidism. Serum T₃ and T₄ levels were reduced significantly in hypothyroid rats whereas these levels were significantly elevated in hyperthyroid rats as compared to euthyroid rats thereby confirming the validity of the model. Kinetic studies revealed a significant increase in the initial and equilibrium uptake of Zn⁺⁺ in both intestinal and renal BBMV of hyperthyroid rats in comparison to hypothyroid and euthyroid rats. By RT-PCR, Slc39a10 mRNA expression was found to be significantly decreased in hypothyroid and increased in hyperthyroid as compared to euthyroid rats. These findings are in conformity with the immunofluorescence studies that revealed markedly higher fluorescence intensity at periphery of both intestinal and renal cells isolated from hyperthyroid rats as compared to hypothyroid and euthyroid rats. Higher expression of Zip10 protein in hyperthroid group was also confirmed by western blot. These findings suggest that expression of zinc transporter protein Zip10 (Slc39a10) in intestine and kidney is positively regulated by thyroid hormones.     

Specific ganglioside changes in extraneural tissues of adult rats with hypothyroidism

Adults rats with hypothyroidism were prepared by administration of 6-propyl-2-thiouracil (PTU) or methimazole, and the tissues were examined for their gangliosides through methods including glycolipid-overlay techniques. Normal thyroid tissue contained GM3, GD3, and GD1a as the major gangliosides, with GM1, GD1b, GT1b, and GQ1b in lesser amounts. The goitrous tissue of PTU-induced hypothyroid rats had higher concentrations of GM1 and GD1a with a concomitant decrease of GM3. The amount of GT3 in thyroid tissue was increased in hypothyroid animals. While normal liver tissue had a complex ganglioside pattern with a- and b-series gangliosides, the PTU-induced hypothyroid tissue showed a simpler ganglioside profile that consisted mainly of a-series gangliosides with almost undetectable amounts of b-series gangliosides. The expression of c-series gangliosides was suppressed in the hypothyroid liver tissue. Heart tissue had higher contents of GM3 and GT3 than control. No apparent change was observed in the compositions of major and c-series gangliosides in other extraneural tissues (i.e., kidney, lung, spleen, thymus, pancreas, testis, skeletal muscle, and eye lenses), and neural tissues (i.e., cerebrum and cerebellum) from PTU-induced hypothyroid rats. The ganglioside changes of thyroid, liver, and heart tissues were reproduced in corresponding tissues of methimazole-induced hypothyroid rats. These results suggest that hypothyroid conditions affect the biosynthesis and expression of gangliosides in specific tissue and cell types.     

3,5-Diiodo-L-Thyronine Activates Brown Adipose Tissue Thermogenesis in Hypothyroid Rats

3,5-diiodo-l-thyronine (T2), a thyroid hormone derivative, is capable of increasing energy expenditure, as well as preventing high fat diet-induced overweight and related metabolic dysfunction. Most studies to date on T2 have been carried out on liver and skeletal muscle. Considering the role of brown adipose tissue (BAT) in energy and metabolic homeostasis, we explored whether T2 could activate BAT thermogenesis. Using euthyroid, hypothyroid, and T2-treated hypothyroid rats (all maintained at thermoneutrality) in morphological and functional studies, we found that hypothyroidism suppresses the maximal oxidative capacity of BAT and thermogenesis, as revealed by reduced mitochondrial content and respiration, enlarged cells and lipid droplets, and increased number of unilocular cells within the tissue. In vivo administration of T2 to hypothyroid rats activated BAT thermogenesis and increased the sympathetic innervation and vascularization of tissue. Likewise, T2 increased BAT oxidative capacity in vitro when added to BAT homogenates from hypothyroid rats. In vivo administration of T2 to hypothyroid rats enhanced mitochondrial respiration. Moreover, UCP1 seems to be a molecular determinant underlying the effect of T2 on mitochondrial thermogenesis. In fact, inhibition of mitochondrial respiration by GDP and its reactivation by fatty acids were greater in mitochondria from T2-treated hypothyroid rats than untreated hypothyroid rats. In vivo administration of T2 led to an increase in PGC-1α protein levels in nuclei (transient) and mitochondria (longer lasting), suggesting a coordinate effect of T2 in these organelles that ultimately promotes net activation of mitochondrial biogenesis and BAT thermogenesis. The effect of T2 on PGC-1α is similar to that elicited by triiodothyronine. As a whole, the data reported here indicate T2 is a thyroid hormone derivative able to activate BAT thermogenesis.     

Thyroid-thymus interactions during development and aging

A good body of experimental and clinical evidences suggests that bidirectional interactions do exist between the neuroendocrine system and the thymus activity. In particular, thymic endocrine activity seems to be strongly influenced by neuroendocrine signals. In this context, studies performed in hyper- and hypothyroid subjects and in the low triiodothyronine (T3) syndrome, which affects premature infants, have clearly shown that thyroid hormones and in particular T3 physiologically modulate thymic peptide secretion. In vitro experiments, with thymic whole-organ cultures, have demonstrated that thyroid hormones exert their action on the epithelial cells of the thymus deputed to synthesize and secrete thymic peptides and that such an effect does not seem to depend on the known permissive action of thyroid hormones.     

Oxidative damage and antioxidant enzyme activities in experimental hypothyroidism

Free radicals are now well known to damage cellular components. To investigate whether age and thyroid level affect peroxidation speed, we examined the levels of malondialdehyde and antioxidant enzyme activities in different age groups of hypothyroid rats. Hypothyroidism was induced in 30- and 60-day-old Wistar Albino rats by the i.p. administration of propylthiouracil (10 mg kg(-1) body weight) for 15 days. While malondialdehyde levels of 30- or 60-day-old hypothyroid rats were increased in liver, they were decreased in the tissues of the heart and thyroid. While glucose-6-phosphate dehydrogenase activity levels did not change in heart, brain and liver tissues of 30-day-old rats, they increased in brain and heart tissues of 60-day-old experimental groups, but decreased in the liver. Catalase activities decreased in the liver and heart of rats with hypothyroidism, but increased in erythrocytes. In control groups while malondialdehyde levels increased in brain, heart and thymus with regard to age, they decreased in plasma. Glucose-6-phosphate dehydrogenase and catalase activities were not affected by age in tissues of the thymus, thyroid and brain, but they were decreased in the heart tissue. The changes in the levels of lipid peroxidation and antioxidant enzyme activities which were determined in different tissues of hypothyroid rats indicate a cause for functional disorder of these tissues. Moreover, there may be changes depending on age at lipid peroxidation and antioxidant enzyme activity levels.     

甲状腺激素对胸腺上皮细胞CK19蛋白表达的影响

目的探讨甲状腺激素对胸腺的发育的影响及可能的机制。方法将12只怀孕4d的大鼠随机分成A组和B组,A组正常饮水,B组孕鼠供以含有0．02％甲巯咪唑的饮水制备仔鼠甲状腺功能低下动物模型,将A组的仔鼠随机分成对照组和甲状腺素钠组,将B组的仔鼠随机分成甲低组和甲低＋甲状腺素钠组。甲状腺素钠组和甲低＋甲状腺素钠组于出生后15d给予腹腔注射甲状腺素钠（0．5mg／kg体重,1次／d）,连续给药25d。所有动物于出生后40d麻醉处死,测定仔鼠的胸腺重量及脏器指数;采用放射免疫技术测定仔鼠血清中三碘甲状腺原氨酸（triiodothyronine,T3）、四碘甲状腺原氨酸（tetraiodothyronine,T4）、促甲状腺激素（thyroid—stimulating hormone,TSH）水平,免疫组织化学技术检测胸腺上皮细胞细胞角蛋白19（cytokeratin 19,CK19）蛋白的表达量。结果与对照组比较,甲状腺素钠组仔鼠血清中T3、T4显著升高,TSH减少,胸腺重量增大;甲低组仔鼠血清中T3、T4明显降低,TSH显著增高,胸腺重量降低,胸腺上皮细胞CK19蛋白表达减少。与甲低组比较,甲低＋甲状腺素钠组仔鼠血清中T3、T4升高,TSH降低,胸腺指数增大,胸腺上皮细胞CK19蛋白的表达明显增多。结论甲状腺激素可以通过影响胸腺上皮细胞CK19的表达量,使胸腺发育或退化。     

Elements in erythrocytes of population with different thyroid hormone status

The contents of elements K, Ca, Fe, Cu, Zn, Se, and Rb in erythrocytes of 78 cases with different thyroid hormone status have been measured by proton-induced X-ray emission and neutron activation analysis. According to the status of thyroid hormones T₃, T₄, TSH, FT₃, and FT₄ detected by radioimmunoassay, the experiment subjects were divided into four groups (i.e., hyperthyroid, hypothyroid, critical [one of thyroid hormones was abnormal], and normal). Elements contents and hormones levels of four groups were analyzed by one-way analysis of variance and correlation using an SPSS/PC statistical package. The results showed that the Se contents of four groups were not significantly different (p<0.05). Zn content of hypothyroid group was significantly higher than those of hyperthyroid and critical groups. The Zn content of the normal group was higher than that of the hypothyroid group and lower than that of the hyperthyroid and critical groups. In the hyperthyroid group, there were significant correlations between elements contents and thyroid hormones levels (except TSH), but not between elements contents and levels of thyroid hormones. However, in the hypothyroid group, relatively strong correlations have been found between elements contents and thyroid hormones levels, especially between Zn and the T₃/T₄ ratio, and between Zn and TSH.     

Hypothyroidism provides resistance to reperfusion injury following myocardium ischemia

A growing body of evidence has demonstrated that reperfusion injury may be mediated, in part, by mitochondrial Ca2+ overload that promotes non-selective permeability of the inner membrane. In this regard it is known that mitochondria from hypothyroid rats are resistant to membrane damage as induced by Ca2+. The purpose of this study was to evaluate the sensitivity of hearts from hypothyroid rats, to the damage by reperfusion, after an ischemic period of 5 min. The results were compared with those from control and hyperthyroid rats. Hypothyroidism was established by surgical removal of the thyroid gland; in turn hyperthyroidism was induced after a daily injection of 2 mg/kg of 3,5,3'-triiodothyronine for 4 days. ECG tracings from hypothyroid rats showed a total absence of post-reperfusion arrhythmias conversely to what was observed in control and hyperthyroid rats. The release of creatine kinase and aspartate amino transferase to the plasma in hypothyroid rats was found to be lower than that found in hyperthyroid and euthyroid rats. The histological studies showed that myocardial fibers from hypothyroid rats were in good condition and retained their striae and a remarkable near absence of edema was clearly observed.     

Lack of An Association between BMI and TSH in Treated Hypothyroid Patients and Euthyroid Controls

Objective: The standard treatment for primary hypothyroidism is replacement with levothyroxine to achieve a thyroid-stimulating hormone (TSH) level within the normal range, (0.45–4.5 mIU/L), which is known to prevent complications including weight gain. While the normal TSH range includes the 95% confidence intervals, it is not known if there is an association between weight and TSH within this interval in treated hypothyroid patients.Methods: We conducted a retrospective analysis of patients treated within the Cooper Health System from January 1 to August 31, 2014. A sample of 245 treated hypothyroid patients and 162 euthyroid controls were studied. Data collected included age, sex, race/ethnicity, height, weight, levothyroxine dose, and diabetes and smoking history.Results: Hypothyroid and control groups were similar in height, weight, body mass index (BMI), and the number of patients with diabetes. There were more females, Caucasians, and nonsmokers in the hypothyroid group. The average TSH was slightly higher in the treated hypothyroid patients versus nonhypothyroid controls (median 1.87 vs. 1.55, P<.01). There was no significant relationship between TSH and BMI in the treated hypothyroid patients or the euthyroid controls.Conclusion: Since no significant relationship was found between BMI and TSH in treated hypothyroidism, there may be no weight reduction benefit gained by adjusting TSH to the lower end of normal range. Patients should be counseled that properly treated hypothyroidism is unlikely to contribute to weight gain. Other treatments such as nutrition and exercise counseling should be offered instead.Abbreviations:BMI = body mass indexTSH = thyroid stimulating hormone     

The importance of thyroid hormone in experimental ovarian cyst formation in gilts

The role of the thyroid gland in ovarian cyst formation in farm animals and in women has rarely been considered. Experimental data on the induction of polycystic ovarian disease (PCOS) in rats indicates the importance of thyroid function to the mechanism of this disorder. The objective of this work was to prove the role of thyroid hormones in gonadotropin-induced cystic ovarian disease (COD) in gilts.In hypothyroid gilts (oral administration of 1 g of methylthioracyl (MTU) daily for 24 days), ovarian cysts were induced by injections of pregnant mares' serum gonadotropin (PMSG) (equine chorionic gonadotropin (eCG)) and human chorionic gonadotropin (hCG) (400 IU and 200 IU daily for 10 days, respectively). Gonadotropins were also injected into hyperthyroid gilts (400 μg of L-thyroxine daily for 24 days). Suitable control groups (no treatment, injected with gonadotropins, hypothyroid by application of MTU and hyperthyroid by administration of L-thyroxine) were set up. Thyroid function was monitored by estimating the total thyroxine in blood plasma using the radio-immunoassay (RIA) method. After treatment, all animals were laparatomized on Days 5–6 of the cycle and the blood samples from peripheral and utero-ovarian veins were collected by cannulation for 2–3 days following surgery. All gilts were then slaughtered and ovaries and other hormonal glands were excised, inspected and preserved for further analysis.The experimental results showed that thyroid hormones in gilts demonstrate an antagonistic influence on the cyst-formative action of gonadotropins. Hypothyroid status increased ovarian sensitivity to gonadotropin action. This was visualised by marked hypertrophy of the ovaries and multiple follicular cysts were also found in both ovaries. In contrast, the hyperthyroid animals showed a reduced sensitivity to the cyst-formative action of gonadotropins (decrease of ovarian dimensions, small numbers of cysts). The mechanism of antagonistic thyroid-gonadotropin relations may be based on negative interactions between thyroid hormones and gonadotropin receptors in the ovaries, and/or on central or peripheral interrelations between thyroid hormones and oestrogens.     

Effect of thyroid state on susceptibility to oxidants and swelling of mitochondria from rat tissues

The effects of the thyroid state on oxidative damage, antioxidant capacity, susceptibility to in vitro oxidative stress and Ca(2+)-induced permeabilization of mitochondria from rat tissues (liver, heart, and gastrocnemious muscle) were examined. Hypothyroidism was induced by administering methimazole in drinking water for 15 d. Hyperthyroidism was elicited by a 10 d treatment of hypothyroid rats with triiodothyronine (10 micro g/100 g body weight). Mitochondrial levels of hydroperoxides and protein-bound carbonyls significantly decreased in hypothyroid tissues and were reported above euthroid values in hypothyroid rats after T(3) treatment. Mitochondrial vitamin E levels were not affected by changes of animal thyroid state. Mitochondrial Coenzyme Q9 levels decreased in liver and heart from hypothyroid rats and increased in all hyperthyroid tissues, while Coenzyme Q10 levels decreased in hypothyroid liver and increased in all hyperthyroid tissues. The antioxidant capacity of mitochondria was not significantly different in hypothyroid and euthyroid tissues, whereas it decreased in the hyperthyroid ones. Susceptibility to in vitro oxidative challenge decreased in mitochondria from hypothyroid tissues and increased in mitochondria from hyperthyroid tissues, while susceptibility to Ca(2+)-induced swelling decreased only in hypothyroid liver mitochondria and increased in mitochondria from all hyperthyroid tissues. The tissue-dependence of the mitochondrial susceptibility to stressful conditions in altered thyroid states can be explained by different thyroid hormone-induced changes in mitochondrial ROS production and relative amounts of mitochondrial hemoproteins and antioxidants. We suggest that susceptibilities to oxidants and Ca(2+)-induced swelling may have important implications for the thyroid hormone regulation of the turnover of proteins and whole mitochondria, respectively.     

Thyroid hormone effects on the State IV proton motive force in rat liver mitochondria

In order to further investigate the mechanisms regulating the control of mitochondrial respiration by thyroid hormone, the proton motive force was measured during State IV respiration in liver mitochondria isolated from euthyroid, hyperthyroid, hypothyroid and T₃-treated hypothyroid rats. The proton motive force was significantly higher in the hyperthyroid group due to an increased pH. The proton motive force of hypothyroid mitochondria was lower than controls due to a decreased membrane potential. The proton motive force for the T3-treated hypothyroid group did not differ from the euthyroid group due to negating changes in the pH gradient and the membrane potential. The intramitochondrial volume was decreased in the hyperthyroid group and unchanged in the other groups. The results indicate that the thyroid status alters the proton motive force in State IV through individual changes in the pH and membrane potential components of the force. The component that changes in hyperthyroid mitochondria is different from that changing in hypothyroid mitochondria.     

Behavior of vitamin A, beta-carotene, retinol binding protein and prealbumin in the plasma of hypo- and hyperthyroid subjects

Plasma concentrations of beta-carotene and retinol, determined by HPLC, and of transport proteins, ascertained by immunodiffusion technique, in hypo and hyperthyroid subjects are reported. In hypothyroid subject a considerable increase in carotene was noted. This was not the case for retinol. In hyperthyroids both beta-carotene and retinol levels were found to be normal. Transport protein (PA and RBP) levels were found to be lower only in cases of hyperthyroidism but unchanged for hypothyroids. According to the Authors the results show that the alteration in plasma carotene levels to be found in hypothyroid subjects is not the direct consequence of a lack of thyroid hormone in the metabolism of vitamin A but the indirect effect of thyroid disease.     

Thyroid hormone may induce changes in the concentration of the mitochondrial calcium uniporter

We explored the possibility that the hormone 3,3',5-tri-iodothyronine can regulate the biosynthesis of the mitochondrial calcium uniporter. To meet this objective experiments on Ca(2+) transport, and binding of the specific inhibitor Ru(360) were carried out in mitochondria isolated from euthyroid, hyperthyroid and hypothyroid rats. It was found that V(max) for Ca(2+) transport increased from 11.67+/-0.8 in euthyroid to 14.36+/-0.44 in hyperthyroid, and decreased in hypothyroid mitochondria to 8.62+/-0.63 nmol Ca(2+)/mg/s. Furthermore, the K(i) for the specific inhibitor Ru(360), depends on the thyroid status, i.e. 18, 19 and 13 nM for control, hyper- and hypothyroid mitochondria, respectively. In addition, the binding of 103Ru(360) was increased in hyperthyroid and decreased in hypothyroid mitochondria. Scatchard analysis for the binding of 103Ru(360) showed the following values: 28, 40 and 23 pmol/mg for control, hyper- and hypothyroid mitochondria, respectively. The K(d) for 103Ru(360) was found to be 30.39, 37.03 and 35.71 nM for controls, hyper- and hypothyroid groups, respectively. When hypothyroid rats were treated with thyroid hormone, mitochondrial Ca(2+) transport, as well as 103Ru(360) binding, reached similar values to those found for euthyroid mitochondria.     

Effects of neonatal hypothyroidism on rat brain gene expression.

To define at the molecular biological level the effects of thyroid hormone on brain development we have examined cDNA clones of brain mRNAs and identified several whose expression is altered in hypothyroid animals during the neonatal period. Clones were identified with probes prepared by subtractive or differential hybridization, and those corresponding to mRNAs altered in hypothyroidism were further studied by Northern blot analysis. Using RNA prepared from whole brains, no effect of hypothyroidism was found on the expression of the astroglial gene coding for glial fibrillary acidic protein. Among genes of neuronal expression, no significant alterations were found in the steady state levels of mRNAs coding for neuron-specific enolase, microtubule-associated protein-2, Tau, or nerve growth factor. N-CAM mRNA increased slightly in hypothyroid brains. In contrast a 2- to 3-fold decrease was found in the mRNA coding for a novel neuronal gene, RC3. This is the first neuronal gene known to be significantly altered at the mRNA level by thyroid hormone deprivation. The abundance of the mRNAs for the major myelin proteins proteolipid protein, myelin basic protein, and myelin-associated glycoprotein, expressed by oligodendrocytes, were also decreased in hypothyroid brains. Developmental studies on RC3 and myelin-associated glycoprotein expression indicated that the corresponding mRNAs accumulate in the brain of normal rats during the first 15-20 days of neonatal life. A similar accumulation occurred in hypothyroid brains, but at much reduced levels. The results demonstrate that thyroid hormone controls the steady state levels of particular mRNAs during brain development.     

Age-dependent inhibition of neuronal protein synthesis by hypothyroidism in the developing rat brain cortex

Neuronal perikarya isolated from developing rat brain cortex were employed for studying the effect of hypothyroidism on RNA and protein synthesis in vitro. Neuronal protein synthesis was inhibited by hypothyroidism during the second week of brain development. Thyroxine treatment in vivo stimulated neuronal protein synthesis in hypothyroid rats. The synthesis of neuronal RNA was depressed by hypothyroidism in 7-day old rats. The inhibition of neuronal protein synthesis due to the lack of thyroid hormaones was restricted to membrane-bound ribosomes. The results suggest that the maturation of the neurone is very sensitive to hormonal imbalance during the critical period of brain development.     

Differential regulation of Na,K-ATPase alpha 1, alpha 2, and beta subunit mRNA and protein levels by thyroid hormone

The purpose of this study was to determine the effect of thyroid status on the Na,K-ATPase alpha isoforms and beta in rat heart, skeletal muscle, kidney, and brain at the levels of mRNA, protein abundance, and enzymatic activity. Northern and dot-blot analysis of RNA (euthyroid, hypothyroid, and triiodothyronine-injected hypothyroids = hyperthyroids) and immunoblot analysis of protein (euthyroid and hypothyroid) revealed isoform-specific regulation of Na,K-ATPase by thyroid status in kidney, heart, and skeletal muscle and no regulation of sodium pump subunit levels in the brain. In general, in the transition from euthyroid to hypothyroid alpha 1 mRNA and protein levels are unchanged in kidney and skeletal muscle and slightly decreased in heart, while alpha 2 mRNA and protein are decreased significantly in heart and skeletal muscle. In hypothyroid heart and skeletal muscle, the decrease in alpha 2 protein levels was much greater than the decrease in alpha 2 mRNA levels relative to euthyroid indicating translational or post-translational regulation of alpha 2 protein abundance by triiodothyronine status in these tissues. The regulation of beta subunit by thyroid status is tissue-dependent. In hypothyroid kidney beta mRNA levels do not change, but immunodetectable beta protein levels decrease relative to euthyroid, and the decrease parallels the decrease in Na,K-ATPase activity. In hypothyroid heart and skeletal muscle beta mRNA levels decrease; beta protein decreases in heart and was not detected in the skeletal muscle. These findings demonstrate that the euthyroid levels of expression of alpha 1 in heart, alpha 2 in heart and skeletal muscle, and beta in kidney, heart, and skeletal muscle are dependent on the presence of thyroid hormone.     

Plasma homocysteine is decreased in the hypothyroid rat

Recent clinical studies have indicated that plasma homocysteine was significantly increased in hypothyroid patients. Since hyperhomocysteinemia is an independent risk factor for cardiovascular disease we investigated homocysteine metabolism in hypothyroid rats. Hypothyroidism was induced in one study by addition of propylthiouracil (PTU) to the drinking water for 2 weeks. In a second study, thyroidectomized and sham-operated rats were used with thyroid hormone replacement via mini-osmotic pumps. Unlike the human hypothyroid patients, both groups of hypothyroid rats exhibited decreased total plasma homocysteine (30% in PTU rats, 50% in thyroidectomized rats) versus their respective controls. Thyroid replacement normalised homocysteine levels in the thyroidectomized rat. Increased activities of the hepatic trans-sulfuration enzymes were found in both models of hypothyroidism. These results provide a possible explanation for the decreased plasma homocysteine concentrations. The hypothyroid rat cannot be used as a model to study homocysteine metabolism in hypothyroid patients.     

Maternal thyroid hormone trajectories during pregnancy and child behavioral problems

There is ample evidence demonstrating the importance of maternal thyroid hormones, assessed at single trimesters in pregnancy, for child cognition. Less is known, however, about the course of maternal thyroid hormone concentrations during pregnancy in relation to child behavioral development. Child sex might be an important moderator, because there are sex differences in externalizing and internalizing behavioral problems. The current study examined the associations between maternal thyroid hormone trajectories versus thyroid assessments at separate trimesters of pregnancy and child behavioral problems, as well as sex differences in these associations. In 442 pregnant mothers, serum levels of TSH and free T4 (fT4) were measured at 12, 24, and 36 weeks gestation. Both mothers and fathers reported on their children's behavioral problems, between 23 and 60 months of age. Latent growth mixture modeling was used to determine the number of different thyroid hormone trajectories. Three trajectory groups were discerned: 1) highest and non-increasing TSH with lowest fT4 that decreased least of the three trajectories; 2) increasing TSH and decreasing fT4 at intermediate levels; 3) lowest and increasing TSH with highest and decreasing fT4. Children of mothers with the most flattened thyroid hormone trajectories (trajectory 1) showed the most anxiety/depression symptoms. The following trimester-specific associations were found: 1) lower first-trimester fT4 was associated with more child anxiety/depression, 2) higher first-trimester TSH levels were related to more attention problems in boys only. A flattened course of maternal thyroid hormone concentrations during pregnancy was a better predictor of child anxiety/depression than first-trimester fT4 levels.