Effect of propranolol on the metabolism of thyroid hormones

The effect of propranolol on thyroxine (T4) and 3,5',3'-triiodothyronine (T3) plasma concentrations, fractional disappearance rates (k), metabolic clearance rates (MCR) and catabolic rates has been investigated in young pigs. The animals were examined in the period 18-24 h after feeding. Plasma concentrations of T3 were lower after treatment with propranolol, but T4 was not significantly affected. The k value of T4 was decreased by propranolol but that for T3 was unaffected. The MCR of T4 and the catabolic rates of both hormones were reduced by propranolol. The reduction in metabolic rate after propranolol is thus probably related to its action on thyroid hormone metabolism.     

Role of thyroid hormones in the modification of diet-induced thermogenesis by propranolol

The effect of thyroid hormones on the reduction in resting metabolic rate by the beta-blocker propranolol has been investigated in young pigs. Oxygen consumption was measured 12 to 20 hr after the last meal in euthyroid and hypothyroid animals on a high or low level of energy intake. The increase in resting metabolic rate in animals on the high energy intake was reduced by propranolol in the euthyroid controls but not in those animals made hypothyroid by methimazole. Thus at least part of the action of propranolol to decrease diet-induced thermogenesis depends on its interaction with thyroid hormones.     

Influence of thermal and nutritional acclimatization on body temperatures and metabolic rate

1. An investigation of the influence of previous thermal and nutritional experience on body temperatures and metabolic rate has been carried out with growing piglets. Littermates were kept, from shortly after birth, at either 10 or 35 degrees C and fed either a high (H) or a low (L) energy intake. At 8 weeks of age the animals were exposed to a series of environmental temperatures of 10, 20, 27 and 35 degrees C for 1.5 hr and their rates of oxygen consumption were determined over the last 45 min. At the end of the session body temperatures were measured. 2. Rectal temperatures measured 24 hr after the start of the last meal were higher at each test temperature in piglets which had been living at 35 degrees C than in those at 10 degrees C. Also, rectal temperatures were higher in those on the H intake for animals which had been living in either the hot or the cold environment. 3. Skin temperature on the back was similar in all groups at any given test temperature although there was a tendency for those on an H intake to have the higher temperatures. Skin temperatures of the legs and ears were higher in the 10H and 10L groups than in the 35H or 35L groups at all the test environmental temperatures; energy intake had little effect. 4. Metabolic rate was greater for the animals on the H than the L intake, for those which had been living at either 10 or 35 degrees C at all the test environmental temperatures. The analysis did not reveal any significant difference related to the overall effect of living temperature, which was independent of energy intake. 5. At thermal neutrality (27 degrees C) there was a significant interaction, between energy intake and normal living temperature, on metabolic rate. Living temperature was found to modify the effect of intake: the difference between the two intakes was greater in those from the cold environment than from the hot.     

Influence of a single meal on fractional disappearance and catabolic rates of 3,5,3'-triiodothyronine and thyroxine over 24 hours

The influence of a single meal on the rates of catabolism of 3,5,3'-triiodothyronine (T3) and thyroxine (T4) was investigated in young pigs. Plasma hormone concentrations, fractional disappearance rates (K), distribution volumes and catabolic rates were estimated during three periods after a meal. For T3, plasma concentration and K were greatest immediately after the meal and decreased progressively. Catabolic rate decreased from 0.45 nmol.hr-1.kg-1 immediately after the meal to 0.28 nmol.hr-1.kg-1 after 24 hr. In a separate investigation, a meal was found to cause an increase in plasma [125I] T4, indicating a shift in the distribution of the hormone pool. Catabolic rate of T4 appeared to be greatest in the period immediately after the meal and decreased to 0.43 nmol.hr-1.kg-1 nearly 24 hr later.     

Relationship between seasonal energy economy and thyroid activity in farm-raised raccoon dogs

1. The levels of thyroid hormones (T3, T4), total lipids and urea in blood serum of adult farmed raccoon dogs (Nyctereutes procyonoides Gray 1834) were monitored year-round, and compared with seasonal changes in body weight and feed consumption during intense, maintenance and restricted fasting feeding. 2. Thyroid hormone levels tended to be low during winter whereas during the rest of the year no marked seasonal differences were observed. That thyroid hormone levels were influenced by altering feed intake suggests the hypothesis that the winter hypothyroidism observed was a result of a decreased level of voluntary feed intake. 3. The colder the temperature was during winter, the less the animals consumed the feed supplied. 4. Neither season nor feed intake level affected serum levels of total lipids or urea. 5. Marked seasonal changes in body weight of the animals were found. From maximum values occurring in early winter their body weight generally dropped about 30% reaching the minimum values in mid-summer. This marked seasonal change was mainly the result of changes in subcutaneous fat reserves.     

The relationship between food intake, body fat and reproductive inhibition in prairie deermice (Peromyscus maniculatus bardii)

1. Reproductively-inhibited deermice selected from four laboratory populations consumed significantly less food than reproductively-proven pairs. 2. Reproductively-inhibited animals predominantly, but not consistently, had reduced total body fat compared with reproductively capable deermice. 3. The per capita food consumption rate of two populations followed for 26 weeks since founding, decreased over time to about 65% of the daily intake of the proven animals used to found the populations. 4. An aggregation or "huddling" behaviour with concomitant reduction in thyroid hormone activity, possibly in response to the density of the "huddle", is suggested as an explanation for these observations.     

Chronic exposure to short photoperiod inhibits free thyroxine index and plasma levels of TSH, T4, triiodothyronine (T3) and cholesterol in female Syrian hamsters

1. Chronic exposure of female Syrian hamsters (Mesocricetus auratus) for 9 weeks to a short photoperiod (10L:14D) depressed the pituitary-thyroid axis as indicated by a drop in circulating titers of thyroid stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3) and the free thyroxine index (FT4I) compared to animals maintained under long photoperiodic conditions (14L:10D). 2. Short day treatment also reduced plasma cholesterol levels. 3. Neither plasma triglycerides, glucose nor growth hormone (GH) levels differed between hamsters exposed to short or long daily photoperiods.     

Differences in growth hormone and prolactin secretion associated with environmental temperature and energy intake

The combined effects of environmental temperature and level of energy intake on plasma concentrations of growth hormone (GH) and prolactin (PRL) have been investigated in 14 week old pigs acclimated to 35 or 10 degrees C on a high (H) or low (L) energy intake (H = 2L). Measurements were made at 15 min intervals between 08.00 and 18.00 hours, after feeding at 17.00 hours on the previous day. Mean values of GH were greater in pigs on the L than H intake and there was a tendency for values to be higher at 35 than 10 degrees C. However, there was wide individual variation within each treatment group and the differences were not statistically significant. Mean PRL concentrations were greater at 35 than 10 degrees C (P less than 0.05). It is concluded that circulating levels of plasma GH do not have a major role in maintaining the differences in growth and morphology of young pigs kept in widely different environmental conditions. However, these differences could be related at least in part to the GH-like properties of PRL.     

Simultaneous observations of iodothyronine content in the thyroid gland, serum and thyroxine 5'- and 5-monodeiodinase activity in liver, during the neonatal period of the pig

Serum T4 and rT3 were high at about 4-12 h after birth, then they decreased to a nadir on day 3 (rT3) and day 7 (T4). Serum T3 concentration fell immediately after birth but then increased to a relatively stable level during the next 2-6 weeks, then fell after weaning. Reciprocal concentration profiles of T4, T3 and rT3 in the thyroid were found. The thyroidal iodothyronine content increased significantly after weaning. In the liver, 5'-monodeiodinating activity, low after birth, rose until day 3 and then decreased concomitantly with T3 in serum. The 5-monodeiodinating activity, high at birth, fell to a nadir at about 3 weeks. No changes in 5- and 5'-deiodinase activity after 3 weeks were observed. Opposite to the variations in absolute content, the iodothyronine relative proportion in thyroid tissue was practically unchanged until weaning time (6 weeks), when they rose. Serum T3/T4 and rT3/T4 ratios increased with age until weaning. The post-weaned pigs had T3/T4 and rT3/T4 ratios about two times smaller than 6-weeks-old pigs. Serum rT3/T3, high after birth, decreased with age. Summarizing, the results indicate that neither changes in the thyroid iodothyronine content nor in the liver T4-monodeiodinating activity can solely account for variations in serum TH during the early neonatal period in the pig. It is suggested that the rapid variations in serum TH levels can reflect changes in the thyroidal secretory activity in preferential T3 secretion and/or blood disappearance rates.     

Bacterial infection (Legionella pneumophila) stimulates fever, metabolic rate and brown adipose tissue activity in the guinea pig

The objective of this study was to assess whether bacterial infection stimulates oxygen consumption and brown adipose tissue (BAT) activity. Guinea pigs infected with Legionella pneumophila showed marked fever and a significant (33%) increase in resting oxygen consumption (VO2), 24h after infection. At this time, food intake and body weight were normal and the in vitro thermogenic activity of BAT taken from infected animals was elevated by 64% above that of control guinea pigs. VO2 and BAT activity fell to control values by 48h as infected animals became moribund and over this period food intake was markedly reduced.     

Hyperiodothyroninaemia of neonates, its significance for thermogenesis

Danowski et al. (1951) were probably the first who showed an increase of PBI in infants shortly after birth. Later a number of investigators presented further evidence on the increased thyroid gland function in newborns. This condition named "neonatal thyroid hyperactivity" [Fisher and Oddie, 1964] was described also in animals. The available data indicate that all the newborn mammals till now studied, independently of the maturation stage of development they reach at birth, display some features of thyroid hyperactivity, but in some it does not lead to hyperiodothyroninaemia. Interspecies differences coincide well with significance of the thyroid hormones for neonatal thermogenesis. There are few sequential studies of the three principal iodothyronines: T4, T3 and rT3 available at present. The most comprehensive data concern infants, newborn lambs and pigs. Immediately after birth, there is a sudden rise in serum thyroid hormone concentrations, with some species differences related to the degree of the increase and to the iodothyronines involved. The course of the postnatal hyperiodothyroninaemia is dependent on the maturation level reached at birth, food intake, and cooling relative to extrauterine environment. At least five main factors contribute to the immediate postnatal hyperiodothyroninaemia: 1) abrupt depletion of the preformed fetal hormonal iodine stores; 2) preferential T3 secretion; 3) increase in the T4 to T3 monodeiodination in the peripheral tissues; 4) a release of thyroid hormone content from peripheral reservoirs to plasma, and 5) action of other hormone(s) concomitantly released at birth. From the point of view of the thermal adaptability, the newborn mammals fall into two distinct groups: first, in which immediately after birth the metabolic rate decreases, and second, in which the metabolic rate increases, after cooling. Our understanding of the role and significance of hormonal factors involved in mechanisms of the postnatal thermogenesis is incomplete. However, some similarities in adaptation to cold in adults and in newborns seem to be relevant. Cold adaptation is accomplished by development of nonshivering thermogenesis (NST) depending on NA. The presence of brown adipose tissue (BAT) is essential for NA thermogenic action. According to the common opinion, based on data from laboratory animals and human baby, non-shivering thermogenesis, but not shivering, predominates in newborns. However, data from domestic animals indicate that shivering thermogenesis may be of comparable or greater thermogenic capacity than NST at birth. Besides, there are some newborns which have little or no BAT and associated NST.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of cold exposure on energy metabolism in the young pig

Twenty-four piglets were weaned at 3 weeks of age and received 615 kJ metabolizable energy/(kg body weight X day). The temperature was reduced from 29 to 25 degrees C by 4 weeks of age. Six pigs were exposed to cold by reducing the temperature to 10 degrees C by 5 weeks of age while the other six were exposed to 23 degrees C. These two temperatures were maintained for 3 weeks. Each week the three pigs closest to the mean weight of each group were used for measurements of heat production for 23 h by open-circuit calorimetry and glucose turnover by continuous infusion of [6-3H]- and [U-14C]-glucose. The animals were sacrificed at 8 weeks of age, a sample of their intercostal muscle was used for in vitro measurement of muscle respiration, and the carcass was analyzed. There was no change in heat production, glucose turnover, and rectal temperature during the 3 weeks of cold exposure, so the data were pooled. Cold exposure increased heat production by 50%, forced mobilization of fat reserves (1000 g over the 3 weeks), and increased glucose replacement rate by 20%. The decline in rectal temperature to 37.6 from 38.8 degrees C could be regarded as a strategy to reduce energy needed to regulate body temperature. In the cold, heat production equalled metabolizable energy intake, but protein deposition was maintained at the same level as that in the pigs at the thermoneutral temperature, using the energy derived from the mobilization of body fat. The increase in Na+-K+ ATPase dependent respiration accounted for 70% of the increase in O2 consumption of muscle from cold-exposed pigs and thus is potentially an important component of cold-induced thermogenesis in the pig.     

Cold adaptation and thyroid hormone metabolism.

Resting oxygen consumption and energy expenditure is sensitive to slight alterations in thyroid function. This means that timing and magnitude of cold adaptation would to some extent depend on thyroid function. Local thyroid hormone metabolism is important for energy expenditure and dissipation of heat in special tissues. Recruitment of brown adipocytes and upregulation of uncoupling protein 1 in mitochondria depends on high tissue T3 concentrations. Most of this T3 is derived from local 5' deiodination of T4. Brown fat is vital for cold exposed mice and rats, and may be important for temperature adaptation in human neonates. The role of thyroid hormone metabolism in adult human cold adaptation has not been finally clarified. Hypothetically, cold exposure may enhance T3 production by deiodination of T4 in skeletal muscle, which may enhance heat production in muscle via a change in muscle fiber type. Another hypothetical possibility is recruitment of brown adipocytes embedded in white adipose tissue in human adults. Understanding cold adaptation in human adults may lead to development of new drugs against obesity.     

Food restriction and refeeding in growing rats.

1. The interrelationship between food intake, body weight and oxygen consumption was analysed at 25 degrees C in growing rats. 3. The experiment was divided into two phases lasting four weeks each. During the first phase the animals were subjected to energy restriction and during the second phase they were allowed ad lib energy intake. Four groups of rats were studied: Control with ad lib food intake and three restricted groups R4, R5, and R6 which received during the first phase 4, 5, and 6 g per day of stock diet in a single meal. 3. The results showed a decrease in body weight and oxygen consumption during the restriction period and a recovering of the latter during the refeeding period, without body weight recovering. 4. It is concluded that an energy conservation mechanism is present during food restriction and for some time after refeeding.     

Effect of gonadotropin (FSH + LH) and thyrotropin (TSH) administered with or without endotoxin at the age of three weeks on the response capacity of the thyroid gland in adult rats

At the age of three weeks the experimental animals received either thyrotropin (TSH), or gonadotropin (FSH + LH), or endotoxin (LPS) alone or in combination. The effectivity of the treatments was evaluated at the age of two months (with or without further hormone treatment). Contrastingly to neonatal TSH treatment, TSH treatment at the age of three weeks did not give rise to imprinting. In female animals, however, TSH treatment increased the sensitivity to the related gonadotropin hormone. At the age of three weeks gonadotropin treatment--on its own--did not cause damages to the TSH receptors of the thyroid gland. While in previous experiments neonatal endotoxin treatment damaged considerably the thyroxin production of the adult thyroid gland, after treatments at the age of three weeks no similar effect could be observed. The treatment, however, decreased the sensitivity of the receptors to TSH. In female animals simultaneous administration of endotoxin and TSH led, even without further hormone treatment, to constant increase in T4 level (the increase could also be detected in the adult animal). Imprinting, however, did not develop. In male animals simultaneous administration of endotoxin and gonadotroph hormone decreased considerably the T4 baseline level, and further TSH or gonadotropin treatment was unable to enhance T4 production.     

Extract of Lycopus europaeus L. reduces cardiac signs of hyperthyroidism in rats

Extracts from the plant Lycopus europaeus L. are traditionally used in mild forms of hyperthyroidism. High doses caused a reduction of TSH or thyroid hormone levels in animal experiments, whereas in hyperthyroid patients treated with low doses of Lycopus an improvement of cardiac symptoms was reported without major changes in TSH or thyroid hormone concentrations. Lycopus extract was tested in thyroxine treated hyperthyroid rats (0.7 mg/kg BW i.p.). Co-treatment with an hydroethanolic extract from L. europaeus L. started one week later than T4-application and lasted 5.5 weeks. As reference substance atenolol was used. The raised body temperature was reduced very effectively even by the low dose of the plant extract, whereas the reduced gain of body weight and the increased food intake remained unaffected by any treatment. No significant changes of thyroid hormone concentrations or TSH levels were observed. Lycopus extract and atenolol reduced the increased heart rate and blood pressure. The cardiac hypertrophy was alleviated significantly by both treatment regimes. beta-Adrenoceptor density in heart tissue was significantly reduced by the Lycopus extract or the beta-blocking agent showing an almost equal efficacy. Although the mode of action remains unclear, these organo-specific anti-T4-effects seem to be of practical interest, for example in patients with latent hyperthyroidism.     

Increase in plasma concentrations of 3,5,3'-triiodothyronine and thyroxine after a meal, and its dependence on energy intake

Plasma concentrations of 3,5,3'-triiodothyronine (T3) and thyroxine (T4) were measured before, during and for between 2 and 6 hr following a meal, in young growing piglets. T3 increased after a meal and reached a peak at approximately 60 min. The magnitude of the rise was dependent on both the energy content and nutrient composition of the meal. In animals given either a high or low energy intake baseline values of T3 were similar, whereas there was a difference in the response to a meal (P less than 0.01). Average increases in hormone concentration were 120% (P less than 0.001) and 50% (P less than 0.05) on the high and low intakes respectively. Plasma T4 also increased in those on high intake (P less than 0.025), but no change was detected when the intake was low. The response of T3 to a meal high in either glucose, sucrose, fat or protein was statistically significant except for the protein meal. The rise in T4 after each of these four meals was less consistent, although it did increase significantly after meals high in sucrose or fat. Amongst several possibilities, these results suggest that a meal may induce an increase in secretion of T3 and T4 from the thyroid gland.     

Effects of acute and chronic relaxin-3 on food intake and energy expenditure in rats

The effects of acute and repeated intraparaventricular (iPVN) administration of human relaxin-3 (H3) were examined on food intake, energy expenditure, and the hypothalamo-pituitary thyroid axis in male Wistar rats. An acute high dose iPVN injection of H3 significantly increased food intake 1 h post-administration [0.4+/-0.1 g (vehicle) vs 1.6+/-0.5 g (180 pmol H3), 2.4+/-0.5 g (540 pmol H3) and 2.2+/-0.5 g (1,620 pmol H3), p<0.05 for all doses vs vehicle]. Repeated iPVN H3 injection (180 pmol/twice a day for 7 days) significantly increased cumulative food intake in ad libitum fed animals compared with vehicle [211.8+/-7.1 g (vehicle) vs 261.6+/-6.7 g (ad libitum fed H3), p<0.05]. Plasma leptin was increased in the H3 ad libitum fed group. Plasma thyroid stimulating hormone was significantly decreased after acute and repeated administration of H3. These data suggest H3 may play a role in long-term control of food intake.