Genetic and environmental interrelations between measurements of thyroid function in a healthy Danish twin population

Serum thyrotropin (TSH), free thyroxine (T4), and free triiodothyronine (T3) levels illustrate the thyroid function set point, but the interrelations between these have never been characterized in detail. The aim of this study was to examine the associations between TSH and thyroid hormone levels in healthy euthyroid twins and to determine the extent to which the same genes influence more than one of these biochemical traits; 1,380 healthy euthyroid Danish twins (284 monozygotic, 286 dizygotic, 120 opposite-sex twin pairs) were recruited. Genetic and environmental associations between thyroid function measurements were examined using quantitative genetic modeling. In bivariate genetic models, the phenotypic relation between two measurements was divided into genetic and environmental correlations. Free T4 and free T3 levels were positively correlated (r=0.32, P<0.0001). The genetic correlation between serum free T4 and free T3 levels was rg=0.25 (95% CI 0.14-0.35), suggesting that a set of common genes affect both phenotypes (pleiotropy). The correlation between the environmental effects was re=0.41 (0.32-0.50). From this we calculated that the proportion of the correlation between free T4 and free T3 levels mediated by common genetic factors was 48%. Only 7% of the genetic component of serum free T3 levels is shared with serum free T4. Serum TSH and thyroid hormone levels did not share any genetic influences. In conclusion, thyroid hormone levels are partly genetically correlated genes that affect free T4 levels and exert pleiotropic effects on free T3 levels, although most of the genetic variance for these measurements is trait specific.     

Euthyroid hypothyrotropinemia in children of short stature

Unique association of hypothyrotropinemia with euthyroidism was described in 2 children of short stature. Both had a history of intrauterine growth retardation (IUGR), but showed an appropriate growth rate after infancy (5 cm/y). Growth hormone secretion after provocation tests was normal, whereas TSH response to TRH was absent. With a highly sensitive TSH radioimmunoassay (RIA) and a specific RIA for TSH-alpha-subunit, both responded to a high dose of TRH stimulation. Serum thyroid hormones were within the normal range, while prolactin response to TRH was exaggerated. Exogenous thyroxine (T4) supplement in case 1 did not improve his growth rate, indicating absence of hypothyroidism. Case 2 was treated with stanozolol, which accelerated his growth velocity to 8 cm/y. During the treatment, serum T4 gradually decreased to 50% of the initial level, but blunted TSH response to TRH remained unchanged. These results indicate that their thyrotrophs are resistant to TRH stimulation and the pituitary setpoint of TSH release is unusually high. The exact mechanism involved in maintaining euthyroidism despite hypothyrotropinemia remains to be elucidated, but a common history of IUGR appears to play a role in producing this pituitary-thyroid state.     

Effects of triiodothyronine treatments on body and organ growth and the development of immune function in dwarf chickens

The effects of triiodothyronine (T3) treatments on general body growth, long bone growth, primary lymphoid organ development, antibody production, and serum growth hormone (GH) and thyroid hormone levels were examined in two dwarf strains (sex-linked dwarf--SLD, and autosomal dwarf--ADW) and in a normal-growing control strain (K) of White Leghorn chickens. One-day-old male chicks from each of these strains were assigned to either an untreated control group or to one of the groups receiving a T3 supplement ranging from 0.01 to 1.0 ppm. General body growth and long bone growth were significantly (P less than 0.05) stimulated only within the SLD strain by the intermediate T3 dosages. The 1.0-ppm T3 dosage level resulted in depressed body weights within both the K and ADW strains but produced no significant changes within the SLD strain. Thymic growth was significantly stimulated due to treatments of 0.1 ppm T3 in the SLD strain (P less than 0.05) and 1.0 ppm T3 in both the SLD and ADW strains (P less than 0.001 and P less than 0.05, respectively). Bursal growth was significantly depressed (P less than 0.05) at all T3 dosage levels within the SLD strain while 0.01 and 0.1-ppm T3 treatments resulted in significant bursal growth stimulation in the K and ADW strains, respectively. Concomitant with the depressed bursal growth, antibody production was significantly depressed (P less than 0.05) within the SLD strain at the 1.0-ppm T3 dosage level. Antibody production was not significantly affected by any of the T3 treatments within the control K or ADW strains. Serum T3 levels were significantly increased in all strains by the T3 supplementation but thyroxine (T4) serum levels were affected only within the SLD strain. The 0.01-ppm T3 treatment resulted in a significant increase (P less than 0.05) in serum T4 levels within this strain and treatment group. The only increase (P less than 0.05) in GH levels due to T3 treatments occurred within the same SLD treatment group. The higher T3 treatments resulted in serum GH levels being severely depressed (P less than 0.01) in all strains.     

Serum thyroid hormone profile and trace elements in children receiving valproic acid therapy: A longitudinal and controlled study

Valproic acid (VPA) may affect thyroid hormone profile, causing alteration in serum trace elements concentrations. The aim of this study was to prospectively investigate this relationship in children receiving VPA monotherapy for a period up to 6 months. Serum thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroxine (T4), triiodothyronine (T3), thyroglobuline (TG), selenium (Se), zinc (Zn), and copper (Cu) levels were evaluated at baseline and at the 6th month in all the patients and in the control group. The mean Cu concentration in the 6th months of VPA therapy was significantly lower than that of the control group. TSH level was significantly increased in the patient group whereas FT4 was significantly decreased. The mean TSH level in the 6th month of VPA therapy was significantly higher than that of the control group, whereas mean T4 level was significantly lower. The Cu level in the 6th months of VPA therapy was positively correlated with T4 level. Δlog Cu and ΔTSH were negatively correlated. This study suggests that the alteration in the serum thyroid hormone profile during VPA therapy may result from the reduction in serum Cu levels.     

Maturation of the pituitary-thyroid axis during the perinatal period.

To clarify the maturation process of the pituitary-thyroid axis during the perinatal period, thyrotropin (TSH) response to thyrotropin releasing hormone (TRH) and serum thyroid hormone levels were examined in 26 healthy infants of 30 to 40 weeks gestation. A TRH stimulation test was performed on 10 to 20 postnatal days. Basal concentrations of serum thyroxine (T4), free thyroxine (free T4) and triiodothyronine (T3) were positively correlated to gestational age and birth weight (p less than 0.001-0.01). Seven infants of 30 to 35 gestational weeks demonstrated an exaggerated TSH response to TRH (49.7 +/- 6.7 microU/ml versus 22.1 +/- 4.8 microU/ml, p less than 0.001), which was gradually reduced with gestational age and normalized after 37 weeks gestation. A similar decrease in TSH responsiveness to TRH was also observed longitudinally in all of 5 high responders repeatedly examined. There was a negative correlation between basal or peak TSH concentrations and postconceptional age in high responders (r = -0.59 p less than 0.05, r = -0.66 p less than 0.01), whereas in the normal responders TSH response, remained at a constant level during 31 to 43 postconceptional weeks. On the other hand, there was no correlation between basal or peak TSH levels and serum thyroid hormones. These results indicate that (1) maturation of the pituitary-thyroid axis is intrinsically controlled by gestational age rather than by serum thyroid hormone levels, (2) hypersecretion of TSH in preterm infants induces a progressive increase in serum thyroid hormones, and (3) although there is individual variation in the maturation process, the feedback regulation of the pituitary-thyroid axis matures by approximately the 37th gestational week.     

Adaptation of male and female rats to iodine deficiency

The response of the hypothalamic pituitary axis to chronic iodine deficiency was compared in male and female Sprague-Dawley rats. The animals were kept on a low iodine diet for 12 weeks. Blood samples as well as thyroid and pituitary weights were obtained every two weeks. Baseline values of thyroid weight and serum thyroxine (T4) were similar in both sexes. However, females had lower serum TSH and higher serum triiodothyronine (T3), pituitary weight and pituitary TSH content. After initiation of the low iodine diet, both sexes showed similar decreases in serum T4 and similar increases of serum TSH and thyroid weight. Serum T3, pituitary weight and TSH content remained higher in females throughout the study. Pituitary TSH was directly correlated with serum TSH in both sexes. When adjusted for pituitary TSH and analyzed by a stepwise regression analysis, serum TSH was lower in females suggesting a difference in TSH secretion between males and females. Our studies demonstrate significant sex differences in the regulation of TSH secretion and maintenance of serum T3 level in response to a chronic stimulus.     

Epidermal growth factor in blood and urine of athyreotic adults

The total contribution of the thyroid to epidermal growth factor (EGF) levels in blood and urine was determined in 18 patients cured from thyroid cancer at the time of thyroxine treatment and 6 weeks off it in the state of athyroidism. As compared to the euthyroid state, the athyrodism was associated with a drop in the urinary EGF excretion from 24.8 +/- 8.4 to 11.8 +/- 4.6 ng/mg creatinine (p less than 0.0001) and some increase in the EGF level in blood serum from 159.5 +/- 55.0 to 191.2 +/- 41.0 pM (p = 0.023). We conclude that the thyroid affects the synthesis and/or blood delivery of EGF and is responsible for approximately one half of its urinary excretion.     

Epidermal growth factor (EGF) inhibits stimulated thyroid hormone secretion in the mouse

It is known that epidermal growth factor (EGF) inhibits iodide uptake in the thyroid follicular cells and lowers plasma levels of thyroid hormones upon infusion into sheep and ewes. In this study, the effects of EGF on basal and stimulated thyroid hormone secretion were investigated in the mouse. Mice were pretreated with 125I and thyroxine; the subsequent release of 125I is an estimation of thyroid hormone secretion. It was found that basal radioiodine secretion was not altered by intravenous injection of EGF (5 micrograms/animal). However, the radioiodine secretion stimulated by both TSH (120 microU/animal) and vasoactive intestinal peptide (VIP; 5 micrograms/animal) were inhibited by EGF (5 micrograms/animal). At a lower dose level (0.5 microgram/animal), EGF had no influence on stimulated radioiodine secretion. In conclusion, EGF inhibits stimulated thyroid hormone secretion in the mouse.     

Neonatal hyperthyroidism alters submandibular gland epidermal growth factor response to thyroxine in the adult mouse

Neonatal hyperthyroidism (NH) in the rat is associated with permanent reductions in serum thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations in the adult, changes suggestive of a hypothyroid state. In the adult NH rat, the thyrotroph appears to be more sensitive to the feedback effects of thyroid hormones. To determine whether thyroid hormone sensitive tissues retain their responsiveness to thyroid hormones, the long-term effects of NH on mouse submandibular gland (SMG) epidermal growth factor (EGF) content were examined. NH was induced in female mice by 20 daily subcultaneous injections of 0.4 microgram of T4 per gram of body weight. Control female mice received daily injections of vehicle alone. At 21 days of age, NH and control mice were sacrificed and SMG EGF content was measured by specific radioimmunoassay, SMG EGF content and concentration in 21-day-old NH mice exceeded that of control mice by 2400- and 1500-fold, respectively (P less than 0.001). SMG EGF content and concentration in adult (90-day-old) NH mice were slightly, but not significantly, lower than those of control mice. Mean SMG weight, however, was significantly decreased in adult NH mice (P less than 0.01). Interestingly, SMG content and concentration of EGF in adult NH mice were lower than in 21-day-old NH mice. After 5 days T4 treatment (16 micrograms/d) of adult mice, SMG weight in NH mice increased significantly (P less than 0.01) but was unchanged in control mice. SMG EGF content and concentration increased significantly in both adult NH and control mice (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth,development, and reassessment of hypothyroid infants diagnosed by screening.

Thirty]six neonates in whom hypothyroidism was diagnosed after thyroid stimulating hormone screening were reassessed at 1 year. All had grown satisfactorily and the mental development scores were normal in all except two. Treatment was withdrawn in 32 and persistent hypothyroidism was confirmed in 31 cases. Thyroid stimulating hormone concentrations were raised in one-third of cases before the withdrawal of treatment and this was associated with generally lower concentrations of serum thyroxine (T4) and smaller doses of L-thyroxine than in those cases with normal concentrations of thyroid stimulating hormone. In treating congenital hypothyroidism, serum T4 concentrations should be monitored regularly and the dose of thyroxine adjusted to maintain serum T4 in the upper part of the reference range.     

甲亢患者甲状腺激素水平与血脂代谢相关性分析及临床意义探讨

目的:探讨甲亢患者甲状腺激素水平与血脂代谢指标之间的关系。方法:对160例甲亢患者治疗前后的甲状腺激素(TH)水平、血脂水平进行对照分析。结果:甲亢治疗前后与健康对照组比较,游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)明显增高,促甲状腺激素(TSH)明显降低,差异有统计学意义(P<0.01);总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(LDL-C)、载脂蛋白A(apoAΙ)、载脂蛋白B(apoB)均明显降低,且差异具有统计学意义(P<0.01);低密度脂蛋白胆固醇(HDL-C)无明显变化(P>0.05)。结论:甲状腺激素与脂类代谢密切相关,临床上在诊治甲亢患者时,应当加强血脂水平的监测,以便更好地指导临床诊治,为疾病的发生发展、判断预后提供有价值的实验室检测指标。     

Disparity in the response of sex steroid-binding protein and corticosteroid-binding globulin to thyroxine in the primate

There is uncertainty regarding the differential effects of thyroid hormone on the circulating levels of sex steroid-binding protein (SBP) and corticosteroid-binding globulin (CBG). Therefore, we studied the effects of elevated thyroxine (T4) on SBP and CBG concentrations in serum in 4 baboon (Papio anubis) infants between 6 and 7 mo of age. The infants were given levothyroxine in increasing doses (25 to 600 micrograms) over a 1-mo period until the peripheral T4 levels were 3-4 times higher than baseline values. Each animal served as its own control. Blood samples were obtained at 2- to 3-day intervals prior to and during treatment. Serum T4 was measured by RIA. SBP and CBG were measured by diethylaminoethyl cellulose filter paper assays. Elevations in serum T4 resulted in a dose-response increase in circulating SBP concentrations with a maximal increase at the 600-micrograms dose of T4 (p less than 0.001). In contrast, significant elevations in peripheral CBG levels occurred with 50 and 100 micrograms of T4 (p less than 0.025 and p less than 0.01, respectively), but decreased thereafter with higher doses of T4. At the 600-micrograms dose of T4, CBG concentrations returned to baseline values. We conclude that in the baboon, T4 increases the circulating levels of SBP in a graded fashion, while the effect on CBG is biphasic.     

A case of hypothyroidism with simultaneous presence of stimulating type anti-thyrotropin (TSH) receptor antibodies and anti-thyroxine (T4) autoantibodies.

We have examined a hypothyroid patient with stimulating type anti-thyrotropin (TSH) receptor antibodies and without blocking type anti-TSH receptor antibodies. Although she had high serum TSH (240 microU/ml) and low free triiodothyronine (FT3, 0.49 pg/ml) concentrations, which agree with physical findings of hypothyroidism, she had an unusually high free thyroxine (FT4) concentration (3.56 ng/dl). Incubation of her serum with 125I-T4, followed by precipitation with 12.5% polyethylene glycol (PEG) disclosed a higher binding of 125I-T4 (34.4%) than in normal controls, being 5-7%. In addition, binding of 125I-T4 to her serum gamma-globulin was completely displaced by the addition of unlabelled T4. From these results it was concluded that her serum contained anti-T4 autoantibodies. Treatment with synthetic T4 was begun and her thyroid function was monitored by sensitive TSH radioimmunoassay (RIA) and RIA of FT4 after PEG treatment. Since both sensitive TSH RIA and FT4 RIA results after PEG treatment give results concordant with the physical findings, it was concluded that both of the RIA results are useful for the evaluation of thyroid function in patients with thyroid hormone autoantibodies.     

Thyroid hormone levels in the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.

Hypothalamic-pituitary dysfunction and thyroid gland cytomegalovirus inclusions have been described in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). We evaluated 80 patients with AIDS or ARC for the frequency of hypothalamic-pituitary or thyroid gland failure and altered serum thyroid hormone levels due to nonthyroidal disorders. One patient had subclinical hypothyroidism. Of these patients, 60% had low free triiodothyronine (T3) index values and 4% had low free thyroxine (T4) indexes; none of the latter had hypothalamic-pituitary or thyroid gland failure, since all serum cortisol values were greater than or equal to 552 nmol per liter (greater than or equal to 20 micrograms per dl) and all thyrotropin levels were less than or equal to 3 mU per liter (less than or equal to 3 microU per ml), respectively. Those who died had lower total T4 and T3, free T3 index, and albumin levels than those discharged from hospital. Serum total T4 and T3 levels correlated with albumin levels and total T3 with serum sodium levels. Serum total T3 levels best predicted the outcome of the hospital stay (accuracy = 82%). Thus, abnormal serum thyroid hormone levels in AIDS or ARC patients are most frequently due to nonthyroidal disorders, but hypothalamic-pituitary or thyroid gland failure may occur.     

Effects of enterally fed epidermal growth factor on the small and large intestine of the suckling rat

Epidermal growth factor (EGF) has been shown to be present in the milk of several species, including the rat, and to have gastrointestinal effects when given parenterally or orally in pharmacologic doses. We investigated the effect of enteral EGF in physiologic doses on the small intestine and colon of suckling rats. Serum thyroxine (T4) levels were also measured. Rats were gavage-fed by hand with an artificial formula with or without added EGF every 3 h from 11 to 14 days of age. Intake was adjusted to deliver 30 kcal/100 g b.wt./day of formula and 16 micrograms/kg/day of EGF approximating the daily caloric intake, and about twice the estimated daily EGF intake for suckling rats. Weight gain did not differ between groups (fed EGF: 3.8 + 0.2 g; not fed EGF: 3.7 + 0.1 g). The protein content of the whole colon of rats fed an EGF-containing formula was significantly lower and the DNA content significantly higher, than in rats fed formula without added EGF. The protein/DNA ratio was therefore markedly higher in the animals fed formula without added EGF; these effects were most evident in the distal colon. In contrast, there was no effect of EGF on small intestinal protein and DNA content; lactase, sucrase, and maltase activities were likewise unaffected, as was serum T4. These data suggest a physiologic role for breast milk EGF in the development of the suckling rat colon.     

Effects of inorganic iodide, epidermal growth factor and phorbol ester on hormone synthesis by porcine thyroid follicles cultured in suspension.

Porcine thyroid follicles cultured in suspension for 96 h synthesized and secreted thyroid hormones in the presence of thyrotropin (TSH). The secretion of newly synthesized hormones was assessed by determining the contents of thyroxine (T4) and triiodothyronine (T3) in the media and by paperchromatographic analysis of 125I-labelled hormones in the media where the follicles were cultured in the presence and absence of inhibitors of hormone synthesis. The hormone synthesis and secretion was modified by exogenously added NaI (0.1-100 microM). The maximal response was obtained at 1 microM. Thyroid peroxidase (TPO) activity in the cultured follicles with TSH for 96 h was dose-dependently inhibited by NaI. One hundred microM of NaI completely inhibited TSH-induced TPO activity. Moreover, both epidermal growth factor (EGF: 10(-9) and 10(-8) M) and phorbol 12-myristate 13-acetate (PMA: 10(-8) and 10(-7) M) inhibited de novo hormone synthesis. An induction of TPO activity by TSH was also inhibited by either agent. These data provide direct evidences that thyroid hormone synthesis is regulated by NaI as well as TSH at least in part via regulation of TPO activity and also that both EGF and PMA are inhibitory on thyroid hormone formation.     

Relative hypoadiponectinemia, insulin resistance, and increased visceral fat in euthyroid prepubertal girls with low-normal serum free thyroxine

A lower activity of the thyroid axis within the clinical reference range is related to a dysmetabolic phenotype in adult populations. We posited that such an association is already present as early as in prepubertal childhood. Serum thyroid stimulating hormone (TSH) and free T4, body fat (bioelectric impedance), insulin resistance (homeostasis model assessment of insulin resistance (HOMA(IR))), total and high molecular weight (HMW)-adiponectin and serum lipids were assessed in 234 euthyroid prepubertal children (113 boys and 121 girls) attending primary care clinics. Visceral fat (abdominal ultrasound) was measured in a subset of these subjects (n = 147; 74 boys and 73 girls). Explants of visceral adipose tissue from an additional six prepubertal children (three boys and three girls) were used to study the regulation of total and HMW-adiponectin by thyroid hormone. Serum free T4 was in girls independently associated with HMW-adiponectin, HOMA(IR) and visceral fat, so that circulating HMW-adiponectin decreased by 30% (β = 0.305 P < 0.005, R(2) = 0.13) and HOMA(IR) and visceral fat increased, respectively, by 90% (β = -0.255 P < 0.01, R(2) = 0.05) and 30% (β = -0.369, P < 0.005, R(2) = 0.12) from the highest to the lowest tertile of serum free T4. Nonsignificant differences in these parameters were found in boys. Treatment of visceral fat explants with thyroid hormone increased total and HMW-adiponectin by 70% and 53%, respectively, above control values (P < 0.01). In conclusion, a dysmetabolic phenotype, consisting of relative hypoadiponectinemia, insulin resistance and increased visceral fat, is associated with low-normal serum free thyroxine in euthyroid prepubertal girls. These associations may be partly explained by a positive regulation of HMW-adiponectin secretion by thyroid hormone.     

Induction of epidermal growth factor by tri-iodo-L-thyronine in the submandibular glands of mice with testicular feminization

The content of epidermal growth factor (EGF) as a high molecular weight complex (HMW-EGF) in the submandibular glands of mice was measured simply by a single radial immunodiffusion method. In female mice, the amount of HMW-EGF was increased 10-fold by tri-iodo-L-thyronine (T3) and 60-fold by 5 alpha-dihydrotestosterone (5 alpha-DHT). In mice with testicular feminization (Tfm), which are genetically deficient in androgen receptor, T3 but not 5 alpha-DHT increased the HMW-EGF from a non-detectable level to 5.4 +/- 0.94 micrograms/mg protein. It was concluded that EGF is also synthesized under the control of thyroid hormone in vivo, and that androgen was not involved in this induction of EGF by thyroid hormone.     

Optimum replacement dose of thyroid hormone assessed by highly sensitive TSH determination in patients with congenital hypothyroidism

Serum thyroid hormone concentrations were measured in 100 samples from 25 patients with congenital hypothyroidism who were clinically well while receiving L-T4 therapy. Thyroxine concentrations were significantly higher than those of controls (p less than 0.01), while triiodothyronine was not significantly different. These samples were divided into four groups according to serum thyroid stimulating hormone concentrations as measured by highly sensitive immunoradiometric assay (IRMA-TSH). Serum thyroid hormone concentrations were compared among groups. The replacement dose of L-T4 and serum thyroid hormone in groups with undetectable IRMA-TSH were significantly higher than those in groups with normal or increased IRMA-TSH. These results show that serum thyroxine concentrations increase in most patients with congenital hypothyroidism on L-T4 therapy. Therefore, thyroxine concentrations above normal are not necessarily of clinical significance if IRMA-TSH is detectable. Undetectable IRMA-TSH might indicate the necessity for a reduction in the L-T4 replacement dose in patients with congenital hypothyroidism.     

Effects of dietary fish oil on thyroid hormone signaling in the liver

n?3 polyunsaturated fatty acids (PUFAs) present in fish oil (FO) potently decrease serum lipids, which is also an effect of thyroid hormones. Both PUFAs and thyroid hormones affect hepatic lipid metabolism, and here we hypothesized that a long-term diet rich in n?3 PUFAs would enhance thyroid hormone action in the liver. Female rats received isocaloric and normolipid diets containing either soybean oil (SO) or FO during lactation. Male offspring received the same diet as their dams since weaning until sacrifice when they were 11 weeks old. FO group, as compared to SO group, exhibited lower body weight since 5 weeks of age until sacrifice, with no alterations in food ingestion, lower retroperitoneal white fat mass and elevated inguinal fat mass relative to body weight, with unchanged water and lipid but reduced protein percentage in their carcasses. FO diet resulted in lower serum triglycerides and cholesterol. Serum total triiodothyronine, total thyroxine and thyrotropin were similar between groups. However, liver thyroid hormone receptor (TR) β1 protein expression was higher in the FO group and correlated negatively with serum lipids. Liver 5′-deiodinase activity, which converts thyroxine into triiodothyronine, was similar between groups. However, the activity of hepatic mitochondrial glycerophosphate dehydrogenase, the enzyme involved in thermogenesis and a well-characterized target stimulated by T3 via TRβ1, was higher in the FO group, suggesting enhancement of thyroid hormone action. These findings suggest that the increase in thyroid hormone signaling pathways in the liver may be one of the mechanisms by which n?3 PUFAs exert part of their effects on lipid metabolism.