Lower Plasma T3 Research Articles

Maternal low-dose caffeine intake during the perinatal period promotes short- and long-term sex-dependent hormonal and behavior changes in the offspring.

Maternal caffeine crosses the placenta and mammary barriers, reaching the baby and, because his/her caffeine metabolism is immature, our hypothesis is that even a low caffeine intake (250 mg/day), lower than the dose limit recommended by the World Health Organization, can promote caffeine overexposure in the offspring, leading to short- and long-term changes. Pregnant Wistar rats received intragastric caffeine (CAF) (25 mg/Kg/day) or vehicle during the gestation and lactation periods. We evaluated morphometrical, metabolic, hormonal, and behavioral parameters of male and female offspring at different ages. Even a low caffeine intake promoted lower maternal body mass and adiposity, higher plasma cholesterol and lower plasma T3, without changes in plasma corticosterone. Female CAF offspring exhibited lower birth weight, body mass gain and food intake throughout life, and hyperinsulinemia at weaning, while male CAF offspring showed reduced food intake and lower plasma T3 at weaning. At puberty and adulthood, male CAF showed higher preference for palatable food, aversion to caffeine intake and higher locomotor activity, while female CAF only showed lower preference for high fat diet (HFD) and lower anxiety-like behavior. At adulthood, both male and female offspring showed higher plasma T3. Male CAF showed hypertestosteronemia, while female CAF showed hypoinsulinemia without effect on glucose tolerance. A low caffeine intake during the perinatal period affects rat's offspring development, promoting sex-dependent hormonal and behavior changes. Current data suggest the need to review caffeine recommendations during the perinatal period.

Study of thyroid function among COVID-19-affected and non-affected people during pre and post-vaccination.

The novel coronavirus COVID-19 has caused a global pandemic with many long-ranging effects on the physiological balance of the human body. The impact of COVID-19 on the thyroid axis remains uncertain. Our aim was to assess the long-term consequences of COVID-19 infection and its vaccination with thyroid hormones. Thirty laboratory-confirmed COVID-19-positive patients with no vaccination record, thirty COVID-19-negative patients with vaccination records, and ten healthy subjects were retrospectively, and cross-sectionally enrolled in this study. An ELISA assay was performed to evaluate thyroid function tests, including the total triiodothyronine (TT3), total thyroxine (TT4), and thyroid stimulating hormone (TSH). We found decreased levels of TT3, average or low plasma T4 levels, and standard or slightly decreased TSH levels in unvaccinated COVID-19-positive patients than in the healthy group, while the vaccinated COVID-19-negative group had normal thyroid hormone levels compared to controls. The correlation between TT3 and TSH levels gradually shifted from no association to a negative pattern in the unvaccinated COVID-19-positive group. Again, a highly significant negative correlation between TSH and TT3 was observed on days above 150, although a slight fluctuation was noted on day 90. This pilot study from Bangladesh shows that abnormalities in thyroid function can be observed during COVID-19 infection and after vaccination, which gradually recovers over time.

Manipulating plasma thyroid hormone levels alters development of endothermy and ventilation in nestling red-winged blackbirds.

Thyroid hormones are key regulators of development and metabolism in vertebrates. During the nestling period, young of altricial species transition from an ectothermic phenotype to an endothermic phenotype. Red-winged blackbirds are an altricial species that exhibit an increase in plasma 3,3', 5-triiodo-L-thyronine (T3) levels during the first 5days post-hatch (dph), begin to develop endothermic metabolic responses by 7 dph, and fledge within 10 days of hatching. We propose that thyroid hormones play an important role in regulating development of endothermy during the nestling period in altricial birds. To better understand the effects of thyroid hormones on endothermic metabolic development in an altricial species, we treated nestling red-winged blackbirds on 2, 3, and 5 dph with either methimazole (MMI) to induce hypothyroidism or supplemental T3 to induce hyperthyroidism. We then measured on 5, 7, and 9 dph morphology and whole animal O2 consumption ( ) and ventilation in the thermal neutral zone and during gradual cooling. Treatment of nestlings with MMI resulted in lower plasma T3 levels on 5 dph that recovered by 7 dph, while supplementing with T3 did not affect plasma T3 levels on 5, 7 and 9 dph. Treatment with MMI resulted in smaller nestlings with smaller hearts and structural characters such as wing chord and femur length, but larger lungs and kidneys. Treatment with T3 produced smaller nestlings with smaller body masses and shorter femur and tarsus lengths. The development of and ventilation endothermic responses to gradual cooling in MMI treated nestlings were delayed when compared with control nestlings. In 9 dph nestlings, hypothyroidism resulted in alterations in the responses of ventilation frequency and tidal volume to cooling when compared with the control nestlings. Supplemental T3 had no effect on the development of and ventilation in the thermal neutral zone or in response to cooling. Our data suggest plasma thyroid hormone levels play an active role in the systemic development of endothermic capacity and the development of ventilatory control. In the nestling avian, multiple systems develop in concert to produce an endothermic phenotype, but reduced thyroid hormone delays maturation of endothermic capacity.

Short and long-term effects of bisphenol S (BPS) exposure during pregnancy and lactation on plasma lipids, hormones, and behavior in rats

Bisphenol S (BPS) has replaced bisphenol A (BPA), a known non-persistent endocrine disrupting chemical, in several products. Considering that little is known regarding BPS effects, especially during critical windows of ontogenetic development, and that BPA, which is quite similar to BPS, is know to be transferred to the offspring via the placenta and milk, in the present study we investigated the behavioral, biochemical and endocrine profiles of Wistar rats born from dams that were BPS-exposed [groups: BPS10 (10 μg/kg/day), BPS50 (50 μg/kg/day)] during pregnancy and lactation. Due to the non-monotonic dose-response effect of bisphenol, the data of both BPS groups were directly compared with those of the controls, not to each other. Males and females were analyzed separately. At weaning, male BPS50 offspring had hypotriglyceridemia and hyperthyroxinemia, whereas BPS50 females showed higher 25(OH)D levels. At adulthood, BPS offspring of both sexes had lower food intake. BPS males showed lower visceral adiposity. BPS50 females had smaller fat droplets in brown adipocytes. BPS males showed higher anxiety and higher locomotor activity, while BPS10 females showed lower exploration. During a food challenge test at adulthood, BPS males consumed more high-fat diet at 30 min. BPS10 females initially (at 30 min) consumed more high-fat diet but, after 12 h, less of this diet was consumed. BPS50 males had hypertriglyceridemia and lower plasma T3, while BPS females showed lower plasma T4. BPS10 females had lower progesterone, whereas BPS50 females had higher plasma 25(OH)D. Maternal BPS exposure has adverse effects on the triacylglycerol, hormones levels and behavior of the progeny. Furthermore, the increased preference for the fat-enriched diet suggests an increased risk for obesity and its health consequences in the long term.

Risk factors for low plasma thyroxine and high plasma thyroid-stimulating hormone concentrations in dogs with non-thyroidal diseases.

The aim of the current study was to identify independent risk factors for thyroid axis alterations in dogs with non-thyroidal diseases. In this retrospective cross-sectional study, data and plasma samples from 207 dogs with non-thyroidal diseases was used. The involvement of various factors (disease severity, sex, age, breed, category and duration of disease, and medication) in the alteration of plasma thyroxine (T4) or thyroid-stimulation hormone (TSH) concentrations was analyzed using multivariate logistic regression. Among the 207 dogs analyzed, 99 (47.8%) had low plasma T4 concentrations, while 45 (21.7%) had high TSH concentrations. Intact male sex [odds ratio (OR), 3.25; 1.67–6.35; P<0.001], Labrador Retrievers (OR, 18.70; 2.32–151.00; P=0.006), moderate (OR, 2.39; 1.21–4.74; P=0.012) and severe diseases (OR, 6.84; 2.27–20.70; P<0.001) were associated with increased risk for low plasma T4 concentrations. Meanwhile, intact male (OR, 3.93; 1.51–10.30; P=0.005), spayed female (OR, 4.22; 1.59–11.20; P=0.004), older age (OR, 2.73; 1.28–5.84; P=0.009), and Miniature Dachshunds (OR, 5.39; 2.38–12.20; P<0.001) had increased risk for high plasma TSH concentrations. Disease severity had been determined as an independent risk factor for canine NTIS. In addition, sex, age and breed were also associated with thyroid axis alterations in dogs with non-thyroidal diseases.

Effects of maternal bisphenol A on behavior, sex steroid and thyroid hormones levels in the adult rat offspring

AimsBisphenol A (BPA), an endocrine disruptor used in industrial applications, has been detected in both placenta and milk. We studied the effects of BPA exposure during pregnancy and lactation on body composition, palatable food intake, biochemical, hormonal and behavioral profiles of young and adult Wistar rat offspring. Main methodsFemale rats were divided into: control, BPA10 (10 μg/kg/day) and BPA50 (50 μg/kg/day). BPA was administered by gavage to dams from gestation until the end of lactation. Euthanasia occurred at weaning [postnatal day (PN) 21] or adulthood (PN180). Key findingsAt weaning, BPA10 female pups had higher plasma cholesterol and triacylglycerol. BPA10 male pups showed lower plasma T3. BPA10 pups of both sexes had higher plasma progesterone, testosterone and estradiol. At adulthood, females of both BPA groups had lower food intake and higher insulinemia, whereas males had lower visceral fat, lower progesterone and testosterone concentrations. BPA10 females and males had lower T4 levels, while only males showed lower estradiol. BPA50 females showed lower fat mass, higher lean mass and lower corticosteronemia, while males had lower food intake. In the feeding study, BPA10 males ate more fat at 30 min, while BPA10 females and males ingested less fat after 12 h. BPA10 females showed hyperactivity while both groups showed less exploration. SignificanceMaternal exposure to BPA during gestation and lactation, even at low doses, induces life-long changes in the regulation of metabolic homeostasis of the progeny, affects sex steroids and thyroid hormones levels, compromises behavior, but does not lead to obesity or dyslipidemia.

Growing goats of different sexes have distinct metabolic responses to continuous feed restriction

The objective of the present study was to investigate the effect of sex on the hormonal and metabolic changes in growing goats subjected to levels of feed restriction. We used 72 Saanen kids, including 24 intact males, 24 castrated males and 24 females with initial bodyweight of 15.76 ± 0.174 kg and initial age of 108.4 ± 18.86 days respectively. A split-plot design was employed (3 sexes = intact males, castrated males, and females; 3 levels of feed restriction = 0% (ad libitum), 25% and 50%). Groups of three goat kids were formed by sex (each goat eating one level of feed restriction); goats of each group were slaughtered when animals fed ad libitum reached 30 kg bodyweight. Fat and protein deposition were calculated by the difference between the determinations performed on samples of homogenates of control animals slaughtered at the start of the experiment and the experimental animals. Blood samples were collected every 10 days to evaluate glucose, total protein, albumin, urea, creatinine, cholesterol, non-esterified fatty acid, β-hydroxybutyrate, aspartate aminotransferase, gamma glutamyltransferase, creatine kinase, triiodothyronine (T3), thyroxine and insulin-like growth factor. Females presented greater fat deposition than did castrated and intact males, regardless of feed restriction (P &lt; 0.0001). Protein body retention (kg) was affected only by feed restriction (P &lt; 0.0001). In females, aspartate aminotransferase activity was greater in those subjected to 50% feed restriction (83.83 ± 4.96 U/L). Regardless of sex, the greatest serum β-hydroxybutyrate concentration was observed when animals were subjected to 50% feed restriction (P &lt; 0.0149). Plasma concentration of insulin-like growth factor 1 was similar in castrated and females, being lower than in intact males. Intact males showed lower plasma T3 concentration than did females (P &lt; 0.05). Females changed their glycolytic metabolism to retain fat deposition even under feed restriction, whereas males mainly changed their protein metabolism to retain protein synthesis, and were less affected by feed restriction.

Incubation temperature alters thermal preference and response to heat stress of broiler chickens along the rearing phase

The current study aimed to investigate whether embryonic temperature manipulation may alter thermal preference throughout the rearing phase of broiler chickens and how this manipulation may affect response to thermal challenge, metabolism, growth rate and feed intake rate. Eggs were exposed to a constant incubation temperature [machine temperatures: 36°C (Low), 37.5°C (Control), and 39°C (High); eggshell temperature of 37.4 ± 0.08°C, 37.8 ± 0.15°C, and 38.8± 0.33°C, respectively] from d 13 till hatching. Low treatment chickens showed lower plasma T3 and GH levels at d 1 of age and lower T3 level at d 42 of age compared to the Control treatment. Preferred ambient, rectal temperature, T4 level, growth rate, food intake rate, and response to thermal challenge were not altered in these chickens. On the other hand, High-treatment chickens exhibited high preferred ambient temperature and rectal temperature during the first 2 wk post-hatch, lower plasma T3 level at d 21 and 42 and a delayed increase in respiratory movement in response to thermal challenge compared to the Control treatment. However, chickens subjected to the Control and High treatments did not differ in T4 and GH level and performance. We conclude that exposure to high temperature during late embryonic development has long-lasting effects on the thermoregulatory system of broiler chickens by affecting the heat tolerance of these chickens. Moreover, the preferred ambient temperature of the chickens from heat-treated eggs correspond to those recommended for the strain under study, whereas for the cold-treated and control-chickens it was 1°C below, indicating that incubation temperature might have consequences on the ambient temperature chickens require during the rearing phase.

Incubation Temperature during Fetal Development Influences Morphophysiological Characteristics and Preferred Ambient Temperature of Chicken Hatchlings.

Skin and feather characteristics, which play a critical role in body temperature maintenance, can be affected by incubation circumstances, such as incubation temperature. However, no study to date has assessed the influence of incubation temperature during the fetal stage on morphometric characteristics and vascular development of the skin, feather characteristics, and their relationship to hormone levels and preferred temperature in later life in chickens. Broiler breeder eggs were exposed to low (36°C), control (37.5°C), or high (39°C) temperatures (treatments LT, CK, and HT, respectively) from day 13 of incubation onward, because it is known that the endocrine axes are already established at this time. During this period, eggshell temperature of HT eggs (38.8±0.33°C) was higher than of LT (37.4±0.08°C) and CK eggs (37.8 ±0.15°C). The difference between eggshell and incubator air temperature diminished with the increasing incubation temperature, and was approximately zero for HT. HT hatchlings had higher surface temperature on the head, neck, and back, and thinner and more vascularized skin than did CK and LT hatchlings. No differences were found among treatments for body weight, total feather weight, number and length of barbs, barbule length, and plasma T4 concentration. LT hatchlings showed lower plasma T3 and GH, as well as lower T3/T4 ratio and decreased vascularity in the neck, back, and thigh skin compared to CK hatchlings. On the other hand, HT hatchlings had decreased skin thickness and increased vascularity, and preferred a higher ambient temperature compared to CK and HT hatchlings. In addition, for all treatments, surface temperature on the head was higher than of the other body regions. We conclude that changes in skin thickness and vascularity, as well as changes in thyroid and growth hormone levels, are the result of embryonic strategies to cope with higher or lower than normal incubation temperatures. Additionally exposure to increased temperature during incubation is an environmental factor that can exert early-life influence on ambient temperature preference of broiler hatchlings in later life.

A Modest Protective Effect of Thyrotropin against Bone Loss Is Associated with Plasma Triiodothyronine Levels.

BackgroundThe independent skeletal effect of thyrotropin (thyroid stimulating hormone, TSH) has been suggested in animal studies. However, clinical data on the association between bone loss and variations in TSH levels is inconsistent. This study aimed to investigate the relationship between TSH levels and bone mineral density (BMD).MethodsWe conducted a cross-sectional study with 37,431 subjects (33,052 cases with euthyroidism and 4,379 cases with subclinical thyroid dysfunction) aged over 35 years. We performed thyroid function tests and measured BMD at the lumbar spine, femur neck, and total hip.ResultsLevels of TSH and T3 were positively correlated in women (r = 0.076, P = 0.001) and uncorrelated in men. In both men and women, TSH levels correlated positively and T3 levels correlated negatively with BMD at all skeletal sites in age and body mass index adjusted analyses. BMD increased steadily with TSH levels from the subclinical hyperthyroid to subclinical hypothyroid range in subjects with T3 levels in the highest tertile (119.5–200.0 ng/dL), but was no longer significant in subjects with lower plasma T3 levels.ConclusionsThe variations in TSH levels within the euthyroid and subclinical range were positively correlated with BMD in healthy men and women. The negative effect of T3 on BMD appears to be compensated for by increased TSH in subjects with plasma T3 levels in the upper normal range.

Angiotensin AT(2) receptor contributes towards gender bias in weight gain.

Obesity is a major disease condition, in turn leading to pathological changes collectively recognized as metabolic syndrome. Recently angiotensin receptor AT2R has been associated negatively with body weight (BW) gain in male mice. However, the gender differences in AT2R and BW changes have not been studied. To understand the gender based role of AT2R involving BW changes, we fed male and female wild type (WT) and AT2R knock out (AT2KO) mice with C57BL6 background with high fat diet (HFD) for 16 weeks. The male AT2KO had higher HFD calorie intake (WT: 1280±80; AT2KO:1680±80 kcal) but gained less BW compared with the WT (WT: 13; AT2KO: 6 g). Contrary to the male animals, the female AT2KO mice with equivalent caloric intake (WT: 1424±48; AT2KO:1456±80 kcal) gained significantly more BW than the WT mice (WT: 9 g; AT2KO: 15 g). The male AT2KO on HFD displayed lower plasma insulin level, less impaired glucose tolerance (GT), and higher plasma T3 compared with WT males on HFD; whereas the female AT2KO mice on HFD showed elevated levels of plasma insulin, more impaired GT, lower plasma T3 and higher free fatty acid and hepatic triglycerides compared with WT females on HFD. Interestingly, compared with WT, AT2KO female mice had significantly lower estrogen, which was further reduced by HFD. These results suggest that AT2R in female mice via potentially regulating estrogen may have protective role against BW gain and impaired glucose tolerance and lipid metabolism.

Deiodinase Activities in Thyroids and Tissues of Iodine-Deficient Female Rats

Severe iodine deficiency is characterized by goiter, preferential synthesis, and secretion of T(3) in thyroids, hypothyroxinemia in plasma and tissues, normal or low plasma T(3), and slightly increased plasma TSH. We studied changes in deiodinase activities and mRNA in several tissues of rats maintained on low-iodine diets (LIDs) or LIDs supplemented with iodine (LID+I). T(4) and T(3) concentrations decreased in plasma, tissues, and thyroids of LID rats, and T(4) decreased more than T(3) (50%). The highest type 1 iodothyronine deiodinase (D1) activities were found in the thyroid, kidney, and the liver; pituitary, lung, and ovary had lower D1 activities; but the lowest levels were found in the heart and skeletal muscle. D1 activity decreased in all tissues of LID rats (10-40% of LID+I rats), except for ovary and thyroids, which D1 activity increased 2.5-fold. Maximal type 2 iodothyronine deiodinase (D2) activities were found in thyroid, brown adipose tissue, and pituitary, increasing 6.5-fold in thyroids of LID rats and about 20-fold in the whole gland. D2 always increased in response to LID, and maximal increases were found in the cerebral cortex (19-fold), thyroid, brown adipose tissue, and pituitary (6-fold). Lower D2 activities were found in the ovary, heart, and adrenal gland, which increased in LID. Type 3 iodothyronine deiodinase activity was undetectable. Thyroidal Dio1 and Dio2 mRNA increased in the LID rats, and Dio1 decreased in the lung, with no changes in mRNA expression in other tissues. Our data indicate that LID induces changes in deiodinase activities, especially in the thyroid, to counteract the low T(4) synthesis and secretion, contributing to maintain the local T(3) concentrations in the tissues with D2 activity.

Beyond Low Plasma T3: Local Thyroid Hormone Metabolism during Inflammation and Infection

Decreased serum thyroid hormone concentrations in severely ill patients were first reported in the 1970s, but the functional meaning of the observed changes in thyroid hormone levels, together known as nonthyroidal illness syndrome (NTIS), remains enigmatic. Although the common view was that NTIS results in overall down-regulation of metabolism in order to save energy, recent work has shown a more complex picture. NTIS comprises marked variation in transcriptional and translational activity of genes involved in thyroid hormone metabolism, ranging from inhibition to activation, dependent on the organ or tissue studied. Illness-induced changes in each of these organs appear to be very different during acute or chronic inflammation, adding an additional level of complexity. Organ- and timing-specific changes in the activity of thyroid hormone deiodinating enzymes (deiodinase types 1, 2, and 3) highlight deiodinases as proactive players in the response to illness, whereas the granulocyte is a novel and potentially important cell type involved in NTIS during bacterial infection. Although acute NTIS can be seen as an adaptive response to support the immune response, NTIS may turn disadvantageous when critical illness enters a chronic phase necessitating prolonged life support. For instance, changes in thyroid hormone metabolism in muscle during critical illness may be relevant for the pathogenesis of myopathy associated with prolonged ventilator dependence. This review focuses on NTIS as a timing-related and organ-specific response to illness, occurring independently from the decrease in serum thyroid hormone levels and potentially relevant for disease progression.

Thyroid Replacement Therapy and Heart Failure

Heart failure (HF) is a major public health and economic problem in Western countries and is one of the most common causes of hospitalization and death. Coronary artery disease is the underlying cause in more than two thirds of chronic HF patients. By 2020, the World Health Organization projects that ischemic heart disease alone will be the most important global cause of morbidity and mortality. The estimated increases in HF-related morbidity and mortality suggest that our understanding of the pathophysiological mechanisms of this syndrome is inadequate. Interest in the role of thyroid hormones (THs) in HF has increased in recent years. The driving considerations can be summarized as follows: (1) the known effects of THs on contractile and relaxation properties of the heart; (2) experimental findings offering strong support for the hypothesis that TH signaling is critical in preserving cardiac structure and performance under normal conditions and after cardiac injury; and (3) evidence that mildly altered TH function is strongly associated with a worsening prognosis in cardiac patients in general and in HF patients in particular. Diastolic function and systolic function are clearly influenced by THs.1 Ventricular contractile function is also influenced by changes in hemodynamic conditions secondary to TH effects on peripheral vascular tone.1 TH homeostasis preserves positive ventricular-arterial coupling, leading to a favorable balance for cardiac work. A study in rats demonstrated that chronic hypothyroidism alone can eventually lead to HF.2 Other studies suggest reduced cardiac tissue triiodothyronine (T3) levels after myocardial infarction (MI) or with development of hypertension by upregulating type 3 deiodinase (D3), which leads to deactivation of T3 and T4 (thyroxine).3–6 This review highlights a growing body of evidence from animal studies and small-scale clinical trials suggesting that low cellular thyroid activity at the cardiac tissue level may adversely affect HF …

Partial pressure of carbon dioxide in the venous blood of young birds as a predictor of ascites susceptibility in broiler chickens

In order to investigate the relationship between carbon dioxide tensions in the venous blood of young chickens and ascites susceptibility, one hundred day-old chickens from two pure broiler breeder lines differing in susceptibility to ascites syndrome were obtained and reared at low environmental temperature. Weekly, blood samples were taken for the determination of blood gas parameters and plasma thyroid hormone levels. Dead birds were examined for lesions of ascites daily and all survived birds were autopsied at the end of the trials. In cold conditioning, the cumulative incidence of right ventricular hypertrophy (RVH) and ascites was 78% (39/50) in fast-growing (line A) and 50% (25/50) in slow-growing (line B) chickens, confirming that line A chickens had higher susceptibility to ascites than line B chickens. At 12 days of age, the mean pCO(2) tension was significantly (P < 0.01) higher in the venous blood of line A than line B chickens. During the experiment, the majority of line A and line B chickens showing RVH and ascites exhibited pCO(2) tensions equal to, or exceeding 50 mmHg at 12 days of age. Additionally, fast-growing chickens showed significantly lower plasma T3 and T4 concentrations than slow-growing chickens. In conclusion, our data indicate that carbon dioxide pressure in the venous blood of early postnatal broiler chickens could be used as a valuable predictor in the selection of birds susceptible to pulmonary hypertension and ascites. The function of thyroid hormones should also be taken into consideration in further selection procedures for meat-type chickens.

Effects of Substitution and High-Dose Thyroid Hormone Therapy on Deiodination, Sulfoconjugation, and Tissue Thyroid Hormone Levels in Prolonged Critically Ill Rabbits

To delineate the metabolic fate of thyroid hormone in prolonged critically ill rabbits, we investigated the impact of two dose regimes of thyroid hormone on plasma 3,3'-diiodothyronine (T(2)) and T(4)S, deiodinase type 1 (D1) and D3 activity, and tissue iodothyronine levels in liver and kidney, as compared with saline and TRH. D2-expressing tissues were ignored. The regimens comprised either substitution dose or a 3- to 5- fold higher dose of T(4) and T(3), either alone or combined, targeted to achieve plasma thyroid hormone levels obtained by TRH. Compared with healthy animals, saline-treated ill rabbits revealed lower plasma T(3) (P=0.006), hepatic T(3) (P=0.02), and hepatic D1 activity (P=0.01). Substitution-dosed thyroid hormone therapy did not affect these changes except a further decline in plasma (P=0.0006) and tissue T(4) (P=0.04). High-dosed thyroid hormone therapy elevated plasma and tissue iodothyronine levels and hepatic D1 activity, as did TRH. Changes in iodothyronine tissue levels mimicked changes in plasma. Tissue T(3) and tissue T(3)/reverse T(3) ratio correlated with deiodinase activities. Neither substitution- nor high-dose treatment altered plasma T(2). Plasma T(4)S was increased only by T(4) in high dose. We conclude that in prolonged critically ill rabbits, low plasma T(3) levels were associated with low liver and kidney T(3) levels. Restoration of plasma and liver and kidney tissue iodothyronine levels was not achieved by thyroid hormone in substitution dose but instead required severalfold this dose. This indicates thyroid hormone hypermetabolism, which in this model of critical illness is not entirely explained by deiodination or by sulfoconjugation.

Regulation of Tissue Iodothyronine Deiodinase Activity in a Model of Prolonged Critical Illness

The low plasma triiodothyronine (T3) observed during prolonged critical illness can be explained in part by suppressed hepatic deiodinase type I (D1) and increased D3 activity. Infusion of thyrotropin-releasing hormone (TRH) can restore D1 and D3 activity in critically ill rabbits, but it remains unknown whether this is a direct effect of TRH or the TRH-induced rise in circulating thyroxine (T4) and T3. To answer this specific question, burn-injured rabbits randomly received a 4-day treatment with saline, T4, T3, T4+T3, or TRH, started on day 4 of the illness. Plasma iodothyronine concentrations, D1 and D3 activity, and T3-responsive gene expression were quantified in liver and kidney. Infusion of T4, T3, or TRH increased circulating T3 levels and hepatic D1 activity. Co-infusion of T3 with T4 enhanced T4 to T3 conversion as demonstrated by lower T4, higher T3, and lower reverse T3 (rT3) levels and tended to further increase hepatic D1 activity. Hepatic D1 activity correlated positively with circulating T3 and the T3/rT3 ratio, but not with T4, rT3, or thyroid-stimulating hormone. During prolonged critical illness, D1 activity is primarily regulated via changes in circulating T3, suggesting that the low plasma T3 concentrations may be important in sustaining low D1 activity in this condition.

Circulating hormones and hypothalamic energy balance: regulatory gene expression in the Lou/C and Wistar rats

To ascertain the mechanisms underlying low caloric intake and low body weight in the Lou/C rat, the circulating hormone levels and gene expression of hypothalamic peptides and receptors important in energy balance and the induction of suppressor of cytokine signalling 3 (SOCS3) gene expression in response to leptin challenge were compared with Wistar rats. Plasma leptin levels were lower in the Lou/C rat, as were levels of rat corticosterone, TSH and T4 but not T3. Ghrelin levels were higher in the Lou/C rat. Total leptin receptor (Ob-R) and the long form of the leptin receptor (Ob-Rb) gene expression were lower in the arcuate (ARC) and ventromedial nuclei (VMN) in Lou/C rat. Ghrelin receptor expression in the ARC and VMN was lower in Lou/C than in Wistar rats. However, agouti gene-related peptide (AgRP) and neuropeptide Y (NPY) gene expression were higher in the Lou/C rat. There was no difference in the level of cocaine- and amphetamine-regulated transcript gene expression in the ARC, but both were higher in the paraventricular nuclei of the Lou/C breed. There was no difference in Ob-R gene expression in, or [(125)I]leptin binding to, the choroid plexus. SOCS3 mRNA induction in response to leptin was lower in the Lou/C rat. This study reveals that the comparatively low plasma leptin, TSH and T4 levels, and high ghrelin levels together with high levels of AgRP and NPY gene expression seen in the Lou/C rat are indicative of a strong drive to eat and decreased energy expenditure, which are in direct opposition to the comparatively low body weight and adiposity of this rat strain.

Effects of environmental temperature on thyroid hormones in the barn owl (Tyto alba)

The basic patterns of thyroid hormones [thyroxine (T4) and 3,3',5-triiodothyronine (T3)] and the T4 and T3 responses induced by thyrotropin releasing hormone (TRH) are reported in captive female barn owls (Tyto alba) during the non-breeding period. The main findings of the study, conducted on a total of 10 owls, are as follow: (1) The thyroid gland of barn owl can be stimulated by the classical TRH stimulation test. (2) T3 response was much more pronounced both under cold (around 10 degrees C) and warm (around 20 degrees C) conditions, whereas T4 response ranged so widely that we could not point out any significant change in it. (3) Basal T3 plasma level was significantly (p = 0.036) higher in birds exposed to cold temperature, and they responded to TRH treatment with a lower plasma T3 elevation than the birds kept in a warm chamber. This pattern, however, cannot be explained by increased food intake, but is in agreement with the fact that enhanced T3 level may account for higher avUCP mRNA expression, which results in higher heat production on the cell level. From the results it is concluded that altering T3 plasma level plays a significant role in cold-induced thermoregulation.

Thyroid hormone and prolactin profiles in male and female turkeys following photostimulation

The turkey hen, a photosensitive bird, will become photorefractory (PR) during the reproductive cycle and will cease laying despite a stimulatory day length. This response is thought to be “programmed” by hormonal events early in the reproductive cycle. The turkey tom, in contrast, produces semen for extended periods and has not been shown to exhibit PR. We compared hormone profiles following photostimulation of hens and toms to assess differences that might program one, but not the other, for PR. We photostimulated with 16 h light per day and measured plasma prolactin (PRL), thyroxine (T4), and triiodothyronine (T3) weekly for 12 wk, and again at 16 and 22 wk. Hens were fed ad libitum, and toms were moderately feed-restricted. Results showed increasing PRL levels following photostimulation in hens, with peak levels occurring at about the time of peak egg production, and declining thereafter. Toms maintained significantly lower concentrations of PRL (P < 0.0001) than hens after 2 wk of photostimulation. A highly significant sex by time interaction in plasma T3 levels was observed due to extreme fluctuations in males. Similar, often reciprocal, fluctuations in mean T4 concentrations also occurred in males. We recycled the toms and repeated blood collections under identical conditions, but with ad libitum feeding to determine if feed restriction may have produced these unusual results. This study revealed an initial significant decline in plasma T3 levels and an increase in T4 levels immediately following photostimulation, and then steady (T4) or slowly rising (T3) levels through 12 wk photostimulation. We conclude that PRL profiles of toms and hens differ markedly during the reproductive cycle, lending support to the suggestion that rising PRL may mediate the onset of PR. Further study is needed to determine if the low plasma T3 levels in males may be related to delayed PR. The extreme fluctuations in plasma T3 and T4 levels of toms receiving relatively mild feed restriction suggest a need for further study of the metabolic effects of feed restriction in turkeys.