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Thyroid hormones (TH) are key regulators of metabolism that could play an important role in altering physiology and energy allocation across life-history stages. Here, we examine seasonal TH dynamics from 345 plasma samples collected from 134 free-living arctic ground squirrels (Urocitellus parryii (Richardson, 1825)) across three consecutive years (2014-2016). We also examine whether unbound levels of triiodothyronine (free [T.sub.3]) in plasma are correlated with total [T.sub.3] levels and total thyroxine ([T.sub.4]) levels, and whether fecal [T.sub.3] metabolite levels correlate with plasma TH levels. We found significant differences in plasma TH levels across stages of the annual cycle, but these differences were highly inconsistent across years. However, within a given time period, pregnant females had lower free [T.sub.3] levels compared with lactating females. We also found that although free [T.sub.3] was correlated with both total [T.sub.3] and total [T.sub.4] in plasma, fecal [T.sub.3] was not positively correlated with plasma TH levels. Given the lack of consistent differences across life-history stages, we suggest environmental heterogeneity may be the primary driver of TH dynamics, masking any potential endogenous seasonal rhythms in TH secretion. We urge caution in the use of fecal [T.sub.3] metabolites as a proxy for circulating levels and encourage further research to understand the observed discrepancy. Key words: Urocitellus parryii, arctic ground squirrel, fecal hormones, reproductive state, thyroid, thyroxine, triiodothyronine. Les hormones thyroidiennes (HT) sont des regulateurs cles du metabolisme qui pourraient jouer un important role dans la modulation de la physiologie et de l'allocation d'energie durant les differentes etapes du cycle de vie. Nous examinons la dynamique saisonniere des HT de 345 echantillons de plasma preleves de 134 spermophiles arctiques (Urocitellus parryii (Richardson, 1825)) vivant en liberte sur trois annees consecutives (2014-2016). Nous tentons aussi de determiner si les concentrations de triiodothyronine libre ([T.sub.3] libre) dans le plasma sont correlees aux concentrations totales de [T.sub.3] et aux concentrations totales de thyroxine ([T.sub.4]), et si les concentrations fecales de metabolites de [T.sub.3] sont correlees aux concentrations plasmiques des HT. Nous relevons des differences significatives des concentrations plasmiques des HT entre les differentes etapes du cycle annuel, mais ces differences sont fortement incoherentes d'une annee a l'autre. Cependant, sur une periode de temps donnee, les femelles gestantes presentent des concentrations de [T.sub.3] libre plus faibles que les femelles en lactation. Nous constatons egalement que, si la [T.sub.3] libre est correlee a la [T.sub.3] totale et a la [T.sub.4] totale dans le plasma, la [T.sub.3] fecale n'est pas positivement correlee aux concentrations plasmiques des HT. Au vu de l'absence de difference coherente entre les differentes etapes du cycle biologique, nous proposons que l'heterogeneitedumilieu pourrait etreleprincipal facteurdemodulationdeladynamique des HT, masquant tout rythme saisonnier endogene eventuel de la secretion des HT. Nous pronons la prudence dans l'utilisation de metabolites fecaux de la [T.sub.3] comme variable substitutive des concentrations en circulation et encourageons la realisation de travaux visant a expliquer l'incoherence observee. [Traduit par la Redaction] Mots-cles : Urocitellus parryii, spermophile arctique, hormones fecales, etat reproducteur, thyroide, thyroxine, triiodothyronine., Introduction Physiological and behavioral flexibility allows free-living vertebrates to cope with environmental heterogeneity, including predictable seasonal changes and unpredictable challenges. Adjustments of physiology and behavior to environmental conditions are often [...]

The aim of this study was to evaluate the impact of intracerebroventricular chronic fibroblast growth factor 21 (FGF21) infusion on hypothalamic-pituitary-thyroid (HPT) axis, energy metabolism, food intake and body weight. Thirty male Wistar albino rats were used and divided into three groups including control, sham (vehicle) and FGF21 infused groups (n = 10). Intracerebroventricularly, FGF21 and vehicle groups were infused for 7 days with FGF21 (0.72 [micro]g/day) and artificial cerebrospinal fluid, respectively. During the experimental period, changes in food intake and body weight were recorded daily. Serum thyroid stimulating hormone (TSH), Triiodothyronine (T3) and thyroxine (T4) levels were measured using ELISA. TRH and uncoupling protein 1 (UCP1) gene expressions were analyzed by using RT-PCR in hypothalamus and adipose tissues, respectively. Chronic infusion of FGF21 significantly increased serum TSH (p < 0.05), T3 (p < 0.05) and T4 (p < 0.001) levels. Additionally, hypothalamic TRH (p < 0.05) and UCP1 gene expressions (p < 0.05) in white adipose tissue were found to be higher than in the vehicle and control groups. While FGF21 infusion did not cause a significant change in food consumption, it caused a reduction in the body weight of rats (p < 0.05). Our findings indicate that FGF21 may have an effect on energy metabolism via the HPT axis. Keywords: FGF21, Intracerebroventricular, Thyroid hormones, UCP1, Author(s): Umit Yilmaz[sup.1], Suat Tekin[sup.1], Mehmet Demir[sup.1], Yilmaz Cigremis[sup.2] and Suleyman Sandal[sup.1] Introduction Fibroblast growth factor 21 (FGF21), a protein 208 amino acids long, is predominantly expressed in the liver [...]

Hypothyroidism and thyrotoxicosis are each associated with an increased risk of fracture. Although thyroxine (T4) is the predominant circulating thyroid hormone, target cell responses are determined by local intracellular availability of the active hormone 3,5,3'L-triiodothyronine (T3), which is generated from T4 by the type 2 deiodinase enzyme (D2). To investigate the role of locally produced T3 in bone, we characterized mice deficient in D2 (D2KO) in which the serum T3 level is normal. Bones from adult D2KO mice have reduced toughness and are brittle, displaying an increased susceptibility to fracture. This phenotype is characterized by a 50% reduction in bone formation and a generalized increase in skeletal mineralization resulting from a local deficiency of T3 in osteoblasts. These data reveal an essential role for D2 in osteoblasts in the optimization of bone strength and mineralization. thyroid hormone metabolism | fracture | hypothyroidism | bone formation | skeleton doi/ 10.1073/pnas.0911346107

Background. The hypothalamo-pituitary-thyroid axis has been widely implicated in modulating the aging process. Life extension effects associated with low thyroid hormone levels have been reported in multiple animal models. In human populations, an association was observed between low thyroid function and longevity at old age, but the beneficial effects of low thyroid hormone metabolism at middle age remain elusive. Methods. We have compared serum thyroid hormone function parameters in a group of middle-aged offspring of long-living nonagenarian siblings and a control group of their partners, all participants of the Leiden Longevity Study. Results. When compared with their partners, the group of offspring of nonagenarian siblings showed a trend toward higher serum thyrotropin levels (1.65 vs 157 mU/L, p =.11) in conjunction with lower free thyroxine levels (15.0 vs 15.2 pmol/L, p = .045) and lower free triiodothyronine levels (4.08 vs 4.14 pmol/L, p = .024). Conclusions. Compared with their partners, the group of offspring of nonagenarian siblings show a lower thyroidal sensitivity to thyrotropin. These findings suggest that the favorable role of low thyroid hormone metabolism on health and longevity in model organism is applicable to humans as well. Key Words: Thyroid--Longevity--Endocrinology. doi: 10.1093/gerona/glp200

Ames dwarf ([Propl.sup.df], df/df) mice lack growth hormone (GH), prolactin, and thyrotropin and live remarkably longer than their normal siblings. Significance of reduced activity of the somatotropic and thyroid axes during development and adulthood on longevity are unknown. Because enhanced insulin sensitivity and reduced insulin levels are among likely mechanisms responsible for increased longevity in these mutants, we compared the effects of GH and thyroxine (T4) replacement on various parameters related to insulin signaling in young and old male df/df mice. The results suggest that altered plasma adiponectin and insulin-like growth factor-1 (IGF-1) and hepatic IGF-1, insulin receptor (IR), IR substrate-1, peroxisome proliferator-activated receptor (PPAR) [gamma], and PPAR[gamma] coactivator-1 [alpha] may contribute to increased insulin sensitivity in Ames dwarfs. The stimulatory effect of GH and T4 treatment on plasma insulin and inhibitory effect on expression of hepatic glucose transporter-2 were greater in old than in young dwarfs. These results indicate that GH and T4 treatment has differential impact on insulin signaling during development and adulthood. Key Words: Ames dwarf--Aging--Insulin--Growth hormone. doi: 10.1093/gerona/glq018

Synopsis In temperate zones, the reproductive physiology of most vertebrates is controlled by changes in photoperiod. Mechanisms for the regulation of photoperiodic gonadal responses are known to differ between mammals and birds: in mammals, melatonin is the photoperiodic signal messenger, whereas in birds, photoperiodic information is received by deep brain photoreceptors. Recently, the molecular mechanism of photoperiodism has been revealed by studies on Japanese quail, which exhibit a most remarkable responsiveness to photoperiod among vertebrates, and molecular cascades involved in photoperiodism have been elucidated. Long-day stimulus induces expression of the [beta]-subunit of thyroid stimulating hormone (TSH-[beta]) in the pars tuberalis (PT) of the pituitary gland, and TSH derived from the PT regulates reciprocal switching of genes encoding types 2 and 3 deiodinases (Dio2 and Dio3, respectively) in the mediobasal hypothalamus (MBH) by retrograde action. Dio2 locally converts prohormone thyroxine ([T.sub.4]) to bioactive triiodothyronine ([T.sub.3]) in the MBH, which subsequently stimulates the gonadal axis. These events have been confirmed to occur in mammals with seasonal breeding, such as hamsters and sheep, suggesting that similar mechanisms are involved among various vertebrates. In addition, nonphotoperiodic mice also appeared to possess the same molecular mechanisms at the hypothalamo-hypophysial level. It has been noted that melatonin regulates the above-mentioned key genes (Dio2, Dio3, and TSH-[beta]) in mammals, while photoperiod directly regulates these genes in birds. Thus, the input pathway of photoperiod is different between mammals and birds (i.e., melatonin versus light); however, the essential mechanisms are conserved among these vertebrates. doi: 10.1093/icb/icp011

Developmental delays consistent with cochlear hypothyroidism contribute to failure to develop hearing in mice lacking Slc26a4/pendrin expression. Am J Physiol Renal Physiol 297: F1435-F1447, 2009. First published August 19, 2009; doi:10.1152/ajprenal.00011.2009.--Mutations of SLC26A4 cause an enlarged vestibular aqueduct, uonsyndromic deafness, and deafness as part of Pendred syndrome. SLC26A4 encodes pendrin, an anion exchanger located in the cochlea, thyroid, and kidney. The goal of the present study was to determine whether developmental delays, possibly mediated by systemic or local hypothyroidism, contribute to the failure to develop hearing in mice lacking Sic26a4 ([Slc26a4.sup.-/-]). We evaluated thyroid function by voltage and pH measurements, by array-assisted gene expression analysis, and by determination of plasma thyroxine levels. Cochlear development was evaluated for signs of hypothyroidism by microscopy, in situ hybridization, and quantitative RT-PCR. No differences in plasma thyroxine levels were found in [Slc26a4.sup.-/-] and sex-matched [Slc26a4.sup.+/-] littermates between postnatal day 5 (P5) and P90. In adult [Slc26a4.sup.-/-] mice, the transepithelial potential and the pH of thyroid follicles were reduced. No differences in the expression of genes that participate in thyroid hormone synthesis or ion transport were observed at P15, when plasma thyroxine levels peaked. Scala media of the cochlea was 10-fold enlarged, bulging into and thereby displacing fibrocytes, which express Dio2 to generate a cochlear thyroid hormone peak at P7. Cochlear development, including tunnel opening, arrival of efferent innervation at outer hair cells, endochondral and intramembraneous ossification, and developmental changes in the expression of Dio2, Dio3, and Tectb were delayed by 1-4 days. These data suggest that pendrin functions as a HC[O.sup.-.sub.3] transporter in the thyroid, that [Slc26a4.sup.-/-] mice are systemically euthyroid, and that delays in cochlear development, possibly due to local hypothyroidism, lead to the failure to develop hearing. DFNB4; Pendred syndrome; thyroid; Tectb; bicarbonate doi: 10.1152/ajprenal.00011.2009.

The aim of the present study was to assess the effects of topically applied triiodothyronine ([T.sub.3]) and thyroxine ([T.sub.4]) on the arterioles of hamster cheek pouch microcirculation in vivo. Microvessels were visualized using a fluorescent microscopy technique. Topical application of [T.sub.3] (3.08, 30.8, 61.5, 307, 615, and 6,150 nM/1) consistently induced dose-dependent dilation of arterioles within 2.0 [+ or -] 0.5 min of administration. The application of [T.sub.4] (150, 257, 514, and 5,140 nM/1) caused different dose-dependent effects: dilation at the three lower doses within 16 [+ or -] 2 min and rhythmic diameter changes at the highest dose. Aging of hamsters did not alter the arteriolar responses to [T.sub.3] and [T.sub.4]. [T.sub.3]-induced dilation was countered by the inhibition of nitric oxide synthase with [N.sup.G]-nitro-Larginine-methyl ester or [N.sup.G]-nitro-L-arginine. Iopanoic acid (IPA), which inhibits types I and II 5'-deiodinase, abolished the dilation elicited by 514 nM [T.sub.4] but did not affect [T.sub.3]-dependent dilation. 6-Propyl-2-thiouracil (PTU), which inhibits type 15'-deiodinase only, did not affect the dilation induced by [T.sub.4]. IPA and PTU did not impair arteriolar dilation induced by acetylcholine or sodium nitroprusside. These results indicate that [T.sub.3] induces arteriolar dilation, likely through nitric oxide release. The local conversion of [T.sub.4] to [T.sub.3] appears to be crucial for the dilation induced by [T.sub.4]. microcirculation; vasodilation; arterioles; nitric oxide; [N.sup.G]-nitro- Larginine methyl ester; [N.sup.G]-nitro-L-arginine; iopanoic acid; 6-propyl-2thiouracil; thyroid hormones

Structure and function were studied for Crocodylus porosus transthyretin (crocTTR), an important intermediate in TTR evolution. The cDNA for crocTTR mRNA was cloned and sequenced and the amino acid sequence of crocTTR was deduced. In contrast to mammalian TTRs, but similar to avian and lizard TTRs, the subunit of crocTTR had a long and hydrophobic N[H.sub.2]-terminal region. Different from the situation in mammals, triiodothyronine ([T.sub.3]) was bound by crocTTR with higher affinity than thyroxine ([T.sub.4]). Recombinant crocTTR and a chimeric construct, with the N[H.sub.2]-terminal region of crocTTR being replaced by that ofXenopus laevis TTR, were synthesized in the yeast Pichia pastoris. Analysis of the affinity of the chimeric TTRs showed that the N[H.sub.2]-terminal region modulates [T.sub.4] and [T.sub.3] binding characteristics of TTR. The structural differences of the N[H.sub.2]-terminal regions of reptilian and amphibian TTRs were caused by a shift in splice sites at the 5' end of exon 2. The comparison of crocodile and other vertebrate TTRs shows that TTR evolution is an example for positive Darwinian evolution and identifies its molecular mechanism. thyroid hormone-binding plasma proteins; choroid plexus; Crocodylus porosus; thyroid hormone homeostasis; eye; lizard; Tiliqua rugosa

Hepatic alcohol dehydrogenase (ADH) activity is higher in female than in male rats. Although sex steroids, thyroid, and growth hormone (GH) have been shown to regulate hepatic ADH, the mechanism(s) for sexual dimorphic expression is unclear. We tested the possibility that the GH secretory pattern determined differential expression of ADH. Gonadectomized and hypophysectomized male and female rats were examined. Hepatic ADH activity was 2.1-fold greater in females. Because protein and mRNA content were also 1.7- and 2.4-fold greater, results indicated that activity differences were due to pretranslational mechanisms. Estradiol increased ADH selectively in males, and testosterone selectively decreased activity and mRNA levels in females. Effect of sex steroids on ADH was lost after hypophysectomy; infusion of GH in males increased ADH to basal female levels, supporting a role of the pituitary-liver axis. However, GH and L-thyroxine ([T.sub.4]) replacements alone in hypophysectomized rats did not restore dimorphic differences for either ADH activity or mRNA levels. On the other hand, [T.sub.4] in combination with intermittent administration of GH reduced ADH activity and mRNA to basal male values, whereas [T.sub.4] plus GH infusion replicated female levels. These results indicate that the intermittent male pattern of GH secretion combined with [T.sub.4] is the principal determinant of low ADH activity in male liver. growth hormone; thyroxine; hypophysectomy; estrogen; testosterone

A recent study demonstrated that feeding a diet with a thermally oxidized fat increases the concentration of thyroxine in plasma of miniature pigs. This study was undertaken to investigate whether the effect of thermally oxidized fats on plasma thyroid hormones is influenced by the supply of vitamin E or selenium. Two experiments were conducted using male Sprague-Dawley rats. The first experiment included eight groups of rats fed diets with either fresh fat or three different types of oxidized fat prepared by heating at 50[degrees]C, 105[degrees]C or 190[degrees]C for 42 d. The diets contained either 25 or 250 mg [alpha]-tocopherol equivalents per kg. The second experiment included four groups of rats fed diets with fresh fat or oxidized fat heated at 55[degrees]C, containing either 70 or 570 [micro]g selenium per kg for 56 d. Rats fed all types of oxidized fats had higher concentrations of free and total thyroxine in plasma than rats fed the equivalent diets with fresh oil; the concentrations of triiodothyronine and thyroid-stimulating hormone did not differ between rats fed fresh and those fed oxidized fats. The effect of the oxidized fat on the plasma thyroxine concentration was completely independent of the supply of vitamin E (expt. 1) and the supply of selenium (expt. 2). Our results confirm that oxidized dietary fats raise the plasma thyroxine concentration and show that this phenomenon is independent of the vitamin E and selenium status. Key Words: * rats * oxidized fat * selenium * vitamin E * thyroxine

Plasma samples from two experiments were processed to determine whether ergot alkaloids associated with endophyte-infected tall rescue altered peripheral thyroxine ([T.sub.4]), triiodothyronine ([T.sub.3]), or cortisol concentrations in cattle. In Exp. 1, seven Angus steers (294 kg) received i.v. bolus injections of saline (SAL), ergonovine maleate (7 mg; EM), or ergotamine tartrate (7 mg; ET) at weekly intervals, and they received all treatments during the study. Blood was sampled every 15 min for 5 h, and treatments were given after h 1. Mean ambient temperature was 34C. Treatment x time affected plasma concentrations of [T.sub.3] (P < .05) and of cortisol (P < .001) but not that of [T.sub.4] (P > .2). Plasma [T.sub.3] concentrations were not affected by SAL, whereas concentrations increased (P Key Words: Cattle, Festuca Poisoning, Ergot Alkaloids, Thyroxine, Triiodothyronine, Cortisol

Woodchucks raised in photoperiods simulating those encountered by boreal and austral woodchucks were used in the investigation of seasonal variation in food intake, oxygen consumption, respiratory quotient and free thyroxine levels in this species. Results reveal that austral woodchucks scored significantly higher in all these parameters compared to their boreal counterparts. Photoperiod has a significant effect on basal metabolism. Metabolic rate and food intake are also affected by levels of free thyroxine.

The signal transduction pathway involved in thyroxine potentiation of the human interferon-gamma (IFN-gamma) antiviral activity was investigated. A comparison was made on the action of thyroxine and milrinone, which has structural homologies with thyroxine. L-thyroxine (T4), triiodothyronine and milnirone increased the antiviral activity of IFN-gamma. Meanwhile, inhibitors of protein kinases C (PKC) and A (PKA) blocked the effects of T4 and milrinone. Thus, T4 potentiation of IFN-gamma's antiviral activity required PKC and PKA but not traditional thyroid hormone receptor.

The kinetics of thyroxin (T4) uptake in mice without transthyretin (TTR) was analyzed to determine the role of thyroxin in the metabolism of (T4). Analysis of radiolabeled [125I]T4 uptake in TTR-null mouse strains indicated the presence of elevated T4 transfer rate from the plasma to the tissues and increase in the percentage of free T4. Furthermore, deficiency in TTR did not affect the availability of T4 to the brain of TTR-null mice.

The effects of L-thyroxine-induced suppression of thyroid-stimulating hormone (TSH) of bone gene expression were analyzed by in situ hydbridization in male Sprague-Dawley rats. Supraphysiological doses of L-thyroxin in rats reduced femoral bone mineral density (BMD) without altering the BMD of the vertebrae. The absence of osteoblast-specific gene expression in vertebral osteoblast compared to femoral osteoblast was due to the inability of L-thyroxin in altering vertebral BMD.

Recent abstinent alcoholics where subjected to serum tracer kinetic studies to determine the effects of recent alcohol abstinence on thyroid hormone metabolism. Recent abstinent alcoholics without overt hepatocellular injury and caloric deprivation exhibited hormone-specific alterations in thyroxine (T4) and 3,5,3'-triiodothyronine (T3) and reverse T3 transfer. Increased T4 and T3 binding to equilibrating tissues due to hepatic protein accumulation were also detected in alcoholics. Ethanol-induced increases in hepatic fatty acid binding proteins also accounted for enhanced T4 and reverse T3 binding.

Transthyretin (TTR) amyloid fibril formation is observed systemically in familial amyloid polyneuropathy and senile systemic amyloidosis and appears to be the causative agent in these diseases. Herein, we demonstrate conclusively that thyroxine (10.8 [[micro]molar]) inhibits TTR fibril formation efficiently in vitro and does so by stabilizing the tetramer against dissociation and the subsequent conformational changes required for amyloid fibril formation. In addition, the nonnative ligand 2,4,6-triiodophenol, which binds to TTR with slightly increased affinity also inhibits TTR fibril formation by this mechanism. Sedimentation velocity experiments were employed to show that TTR undergoes dissociation (linked to a conformational change) to form the monomeric amyloidogenic intermediate, which self-assembles into amyloid in the absence, but not in the presence of thyroxine. These results demonstrate the feasibility of using small molecules to stabilize the native fold of a potentially amyloidogenic human protein, thus preventing the conformational changes, which appear to be the common link in several human amyloid diseases. This strategy and the compounds resulting from further development should prove useful for critically evaluating the amyloid hypothesis - i.e., the putative cause-and-effect relationship between TTR amyloid deposition and the onset of familial amyloid polyneuropathy and senile systemic amyloidosis.

The thyroid hormone, thyroxin, activates protein kinase C and 3',5'-cyclic monophosphate-dependent protein kinase (PKA) to enhance antiviral activity via interferon-gamma (INF-gamma) action. The antiviral activity of HeLa cells was repressed by the inhibition of protein synthesis coupled with cylcoheximidine treatment. A nongenomic mechanism mediates the potentiation action of thyroid hormone which initiates the antiviral activity of INF-gamma.

The increased activity of serine protease enhances the level of mature epidermal growth factor (EGF), following acute ischemic renal injury in rats. Triiodothyronine (T3), produced in the kidney, may stimulate the activity of serine protease that cleaves the EGF precursor. Analysis of the renal thyroid hormone-EGF axis reveals an increase in the level of thyroxine 5'-deiodinase. Postischemic renal injury reduces circulating total thyroxine (T4), free T4 and free T3 but the level of total T3 remains unchanged.

It has been observed that juvenile Atlantic salmon (Salmo salar) undergoing parr-smolt transformation exhibit elevated plasma levels of L-thyroxine (T4). To test if T4 is involved in the development of olfactory function during parr-smolt transformation, late-parr Atlantic salmon were exposed to high levels of T4. The results show that T4 inhibited olfactory responsiveness to L-alanine and reduces the synthesis of 3,5,3'-triiodo-L-thyronine in the brain, indicating a possible role for T4 in the development of odor-learning in juvenile salmonids.

Rast suffering from iron deficiency are unable to control their body temperature effectively perhaps because they are unable to metabolize norepinephrine effectively. However, norepinephrine metabolism acts independently of the thyroid hormone thermoregulatory functioning. This was observed in rats which exhibited lower norepinephrine turnover in their tissues even when treated with thyroxine and triiodothyronine.

A study was conducted to examine the role and determine the amount of insulin-like growth factor I (IGF-I) and its binding proteins (IGFBP) in hyperthyroid rats. An ultrafiltration method measured the amount of circulating levels of free and total IGF-I and IGFBPs while Western ligand blotting identified the proteins. The results revealed that serum total IGF-I and IGFBP remained the same after 13 days of hyperthyroidism. However, animals treated with high amounts of thyroxine exhibited low free serum IGF-I, suggesting that hyperthyroidism in rats increases IGFBPs but reduces free IGF-I.

The effects of dietary protein on plasma cholesterol concentrations are well documented: animal proteins (casein) are hypercholesterolemic compared with plant proteins (soy protein). Although this effect of protein source on plasma cholesterol has been shown in many species, the mechanism is not completely understood. This paper reviews the relationship between dietary protein source and plasma thyroxine concentration. The basic premise is that feeding soy protein lowers plasma cholesterol concentration by causing an increase in plasma thyroxine concentrations. The metabolic changes involving cholesterol that occur when soy protein is fed are discussed. These changes are consistent with changes induced by elevating thyroxine. Data are presented from animal studies showing that feeding soy protein to laboratory animals consistently elevates plasma thyroxine concentrations. Furthermore, this elevation in plasma thyroxine concentrations precedes the change in plasma cholesterol concentrations: a necessary requirement for hypothesizing a causative effect. Possible mechanisms as to how a dietary protein source affects plasma thyroxine are also presented. INDEXING KEY WORDS: soy protein; casein; thyroxine; cholesterol

A study of the influence of thyroxine (T4)-induced cardiac hypertrophy on the decrease in myocardial O2 utilization due to increased cGMP levels by using nitroprusside on control- and T4 hearts of rabbits reveals that nitropusside reduces the cGMP increase and O2 consumption in T4 hearts. Total and basal levels of cGMP are the same in the two groups of animals, and both exhibit similar decreases in O2 consumption.

A study of the relationship between age and chronic thyroxine (T4)-induced angiogenesis by comparing control and T4-treated rats of different age groups reveals that chronic T4-induced angiogenic effects are not restricted to senescence. The enhancement in heart rate due to T4 is offset by capillary and precapillary growth, enabling a normal myocardial perfusion per unit mass. Capillary proliferation and diameter increase lead to normal capillary volume density in T4-treated rats that have cardiac hypertrophy.

Optimal serum factor concentration of 0.1 in epiphyseal chrondrocyte culture promotes morphogenesis of columnar cartilage cells. Removal of serum factors and subsequent administration of thyroxine in a chemically defined medium restores morphogenesis to the normal level, indicating that thyroxine is an essential serum factor. Thyroxine prevents arbitrary alignment of cells and regulates synthesis of type X collagen mRNA and its protein.

Transport of iodothyronines in the liver is ATP-dependent and the transmembrane thyroxine (T4) uptake in the liver is controlled by intracellular energy reserves. Tissue uptake process that is carrier-mediated affects the intracellular metabolism and bioavailability of thyroxine. Fructase reduces the uptake of T4 tracer in the liver by inhibiting the transport of T4 in to intracellular region, while the uptake in the extraceullar pool is unaffected.

The role of age in the initiation of cardiac hypertrophy induced by thyroxine (T4) was studied by exposing prepubescent and senescent rats to T4 for four days. An increase in left ventricular (LV) mass and RNA/LV were observed in both groups within four days. No enhancement of cardiac hypertrophy similar to those seen in hyperthyroid conditions was observed at various LV epinephrine levels. This suggests that cardiac hypertrophy is not induced by norepinephrine nor is it limited to any age group.

The effects of the thyroid hormones triiodothyronine (T3) and thyroxine (T4) on cardiac development without hemodynamic load were examined. The study protocol involved the grafting of embryonic rat myocardium into the anterior eye chamber of adult host rats. The results indicate that exposure to normal levels of the thyroid hormones T3 and T4 are necesary for normal cardiac development. Furthermore, hemodynamic load is also necessary for thyroid hormone-induced cardiac development.

Halogenated organic chemicals are compounds that have one or more chlorine or bromine atoms. Examples of such chemicals include polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), tetrachloro-p-dioxin (TCDD, or simply dioxin), dichlorophenoxy butanoic acid (2,4-DB), and dichlorodiphenyltrichloroethane (DDT). These substances are made in industry and used as insecticides. Previous studies have indicated that these chemicals may cause blood levels of thyroid hormones to be reduced and cause the thyroid gland to become enlarged (hypertrophy). It is not known how these chemicals reduce the levels of thyroid hormones. Transthyretin (TTR) is a protein that binds to and transports thyroxine (a thyroid hormone) in the blood. In order for thyroxine to perform its normal functions it must bind to and be carried in the blood by TTR. It has been hypothesized that PCBs may reduce blood levels of thyroxine by binding to TTR so that the thyroxine cannot bind to it. To investigate this hypothesis, 65 different halogenated organic chemicals commonly used in industry were tested for their ability to prevent thyroxin from binding to its carrier protein, TTR. The results of this study showed that many of the compounds tested were able to bind to TTR and therefore may be able to prevent thyroxine from binding to TTR in the blood. Examples of these chemicals include chlorophenols, dinoseb, bromoxynil and dichlorophenoxybutyric acid. It is suggested that thyroid function be measured in workers exposed to halogenated organic chemicals. (Consumer Summary produced by Reliance Medical Information, Inc.)