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Green & Matty (1963) reported that both metabolic rate and active sodium transport increased within minutes after the addition of thyroxine (T4) to solutions bathing the serosal surface of ventral skin and urinary bladders from the toad, Bufo bufo. The response persisted at least 1 hr. with peak increases in O2 consumption averaging well over 100% for both skin and bladder when determined polarographically. More recently, using standard Warburg manometry, Thornburn & Matty (1964) obtained only about 25% increase in O2 consumption from toad bladders treated with T4 and no response from toad skin. However, skin did respond to triiodothyronine and tetraiodothyroacetic acid with increases of 13 and 8%, respectively. Active sodium transport, measured as short-circuit current, increased about 100 % in bladder and 50 % in skin after exposure of the serosal surface to T4 at a concentration of 10−6 m (Green & Matty, 1963).
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Exposure of experimental animals and man to a cold environment increases the basal metabolic rate, a hot environment decreases it. These changes are believed to be controlled, at least in part, by altered thyroid activity (Pitt-Rivers & Tata, 1959). Gottschalk & Riggs (1952) have shown that the protein-bound iodine (PBI) increases in prolonged cold exposure in man, but similar changes could not be demonstrated in the rat (Rand, Riggs & Talbot, 1952). If the PBI is unaltered during thyroid hyperactivity there is presumably an increased rate of removal of thyroxine from the circulation. Recently many experimental and clinical studies have emphasized the important role of the liver in the metabolism of the thyroid hormones (Kiltgaard, 1953; Vanotti, 1957). Therefore two groups of experiments designed to test the effect of environmental temperature on the hepatic metabolism of thyroxine were carried out.
Distribution of 131I in animals kept at different temperatures
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SUMMARY
1. The hypophysectomized rat does not exhibit any especially prompt or extensive metabolic response to single doses of 3,5,3′-triiodothyronine (T3) or 3,5,3′-triiodothyroacetic acid.
2. The hypophysectomized rat is less sensitive than the thyroidectomized one to oxygen consumption effects of thyroxine (T4) or T3 by repeated injection.
3. In contrast, injection of cortisone produces two or three times as great a rise in the metabolic rate of hypophysectomized animals as in that of normal, thyroidectomized or adrenalectomized-thyroidectomized ones.
4. In all animals, stimulation of oxygen consumption by cortisone plus T4 or cortisone plus T3 was the same as the simple additive action of each component.
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Daily administration of adrenaline over a 10-day period invariably induced significant increases in the metabolic rate of the whole body and of specific tissue (liver, muscle, kidney and brain) of both intact and thyroidectomized lizards except during June (breeding season) when the presence of thyroid hormones was a prerequisite for the stimulation of oxygen consumption by the whole body, muscle, kidney and brain but not by the liver. Corticosterone had no effect on whole body oxygen consumption but stimulated, inhibited or was without influence on the oxygen consumption of individual tissues, depending on the season and the presence or absence of thyroid hormones. It is suggested that adrenaline, due to its temperature-independent calorigenic effect, acts as the emergency hormone for energy release and helps the animal to survive during hibernation (winter months) when almost all the endocrine glands are inactive.
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Radiation Medicine Centre, Bio-Medical Group, Bhabha Atomic Research Centre, Tata Memorial Hospital, Parel, Bombay-12, India
(Received 25 March 1974)
Pendred's syndrome is characterized by familial goitre, nerve deafness and a partial release of radio-iodine from the thyroid on perchlorate administration. This last was thought to be due to impaired activity of peroxidase enzymes or to some abnormality of receptor proteins where iodination occurs. Burrow, Spaulding, Alexander & Bower (1973) reported that peroxidase activity in such patients is normal but studies on thyroidal iodoproteins have shown variable results (Medeiros-Neto, Nicolau, Kieffer & Ulhoa-Cintra, 1968; Milutinovic et al. 1969).
A 22-year-old deaf-mute woman (N.G.) with a goitre which had progressively increased in size from infancy was euthyroid in all respects: basal metabolic rate, 10·0%; serum cholesterol concn, 174·3 mg/100 ml; tri-iodothyronine (T3) red blood cell uptake, 14·6%; stable protein-bound iodine levels, 5·7 μg/100 ml. Radioactive iodine uptake by the thyroid was 65·7%
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SUMMARY
1. Certain analogues of thyroxine have been administered to twenty-six hypothyroid patients and 132 euthyroid hypercholesterolaemic men with coronary heart disease. The analogues studied were d-thyroxine, 3:5:3′:5′-tetraiodothyroformic acid, 3:5:3′:5′-tetraiodothyronamine, 3:5:3′-triiodo-l-thyronine, 3:5:3′-triiodo-d-thyronine, 3:5:3′-triiodothyroacetic acid, 3:5-diiodo-l-thyronine, 3:5-diiodo-d-thyronine and 3:5-diiodothyroacetic acid.
2. In both hypothyroid and euthyroid patients, most of these analogues reduced the serum cholesterol without necessarily elevating the basal metabolic rate (b.m.r.). Nevertheless, in euthyroid patients with coronary heart disease several produced angina in the absence of any change in b.m.r. and this has been regarded as a sign of increased myocardial metabolism insufficient to be reflected in the overall measure of b.m.r. of all tissues. The possible differential effect of these analogues on the oxygen requirements of various tissues is discussed.
3. Although it has been possible to maintain low cholesterol levels for periods up to 3 months during the administration of several of these analogues, the dose required for this purpose was often so close to the dose which provoked angina that most cannot be recommended for widespread administration for the reduction of the hypercholesterolaemia frequently found in patients who have coronary heart disease. d-Thyroxine may prove to be an exception and requires further clinical assessment.
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Leptin is an adipocyte hormone involved in the regulation of energy homeostasis. Generally accepted biological effects of leptin are inhibition of food intake and stimulation of metabolic rate in ob/ob mice, that are defective in the leptin gene. In contrast to these centrally mediated effects of leptin, we are reporting here on leptin effects on glucose incorporation into lipids and glucose decarboxylation in adipocytes isolated from male lean albino rats. Adipocytes previously cultivated (15 h) in the presence of leptin presented a 25% (P < 0.05) reduction of the insulin stimulated incorporation of glucose into lipids. Concurrently, the basal conversion of (U-14C)D-glucose into 14CO2 increased (110%) in the leptin cultivated adipocytes and reached values (1.54 nmol/10(5) cells) similar to the insulin stimulated group (not cultivated with leptin) (1.40 nmol/10(5) cells). In addition, in the presence of insulin, the leptin cultivated adipocytes elicited a 162% (P < 0.05) increase in 14CO2 production that was significantly higher than the increase observed for the not-leptin-cultivated insulin group (92%). We conclude that leptin: 1) directly inhibits the insulin stimulated glucose incorporation into lipids; 2) stimulates glucose decarboxylation, and also potentiates the effect of insulin on glucose decarboxylation in isolated adipocytes. Leptin per se does not alter glucose incorporation into lipids.
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Abstract
The influence of the type of dietary fat on the effects of thyroid hormones was investigated in mice. Hyperthyroidism was achieved by providing thyroid hormones (T3 and T4) in the drinking water. Both hyperthyroid and euthyroid mice (Mus musculus) were fed isoenergetic diets containing 18% (w/w) total lipid but differing in fatty acid composition. Diets were either low in the polyunsaturated linoleic acid (18:2, ω6) and high in saturated fatty acids (SFAs) or low in saturated fats and high in the polyunsaturated fatty acid (PUFA), linoleic acid. Treatments were maintained for 21–22 days. Plasma thyroid hormone levels, standard metabolic rate (SMR), changes in body mass, specific activities of malic enzyme (ME), Na-K-ATPase and glycerolphosphate dehydrogenase (GPDH) of the liver were measured. Fatty acid composition of the liver phospholipids was also determined. Levels of T3 (15–17 nm) and T4 (250–255 nm) were significantly higher in the respective hyperthyroid groups. There was no significant influence of the diet on hormone levels. Hyperthyroidism increased the SMR 37–44% above the euthyroid levels. A significant body weight loss of 14–18% was observed in hyperthyroid mice on the PUFA diet but not in those on the SFA diet. PUFA diet significantly reduced the activity of ME but had no effect on Na-K-ATPase or GPDH activity. Activities of Na-K-ATPase and GPDH were significantly elevated in all hyperthyroid groups. Mice on T4 and PUFA diet showed a highly significant 399% increase in GPDH activity above the euthyroid level. The overall degree of unsaturation of the fatty acids in the liver phospholipids was comparable in all groups. Dietary treatment substantially changed liver membrane fatty acid composition whilst hyperthyroidism resulted in only small changes. The only parameters to show an interaction between dietary fat profile and hyperthyroidism were ME activity, changes in body mass and liver phospholipid fatty acid composition.
Journal of Endocrinology (1995) 144, 431–439
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ABSTRACT
Oxygen consumption (VO2), carbon dioxide production (VCO2), heart rate and the arterial plasma concentrations of glucose, non-esterified fatty acids, thyroxine (T4), 3,5,3′-tri-iodothyronine (T3), TSH, insulin, cortisol and GH were measured before and after feeding a formula milk diet to lambs aged 9, 21, 33 and 46 days. In all age groups, VO2, VCO2 and heart rate increased significantly following feeding and this effect was greatest at 9 days of age. Both VO2 and VCO2 before and after feeding decreased with age. Plasma concentrations of T3 before feeding did not change with age, but plasma T3 levels after feeding were significantly higher in lambs aged 9 days compared with 33 and 46 days. There was no effect of feeding on TSH or age on plasma TSH and T4 concentrations. In all age groups, glucose concentration increased after feeding and was paralleled by a rise in insulin concentration. At 9 and 21 days of age plasma glucose and insulin concentrations reached a plateau after the initial postprandial increase and together with a rise in respiratory quotient was indicative of a stimulation of carbohydrate oxidation. Plasma concentrations of GH increased after feeding at 21 days and older, when the mean growth rate was also stimulated by 75%. Basal metabolic rate and dietary-induced thermogenesis both decreased with age and, as a result, metabolism associated with an increase in GH levels after feeding became more efficient in terms of growth rate after 21 days. It is therefore concluded that there are major endocrine and cardiorespiratory changes in response to feeding of the young lamb which are important in stimulating and/or facilitating its growth and development.
Journal of Endocrinology (1989) 123,295–302
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ABSTRACT
Non-domesticated seasonally breeding ungulates exhibit marked seasonal changes in metabolic rate, voluntary food intake (VFI), pelage growth and moult and hormone secretion. It is not known whether these seasonal rhythms are regulated by the same central processes which control the onset and termination of the breeding season. Here we compare two closely related deer species which have significantly different mating and calving seasons. Seasonal changes in VFI, liveweight, coat growth, plasma prolactin and tri-iodothyronine (T3), and the timing of the breeding season were examined over a 15-month period in six adult post-pubertal red and Père David's deer from January to April the following year. The timing of the seasonal changes in prolactin, T3, VFI and coat growth were all significantly advanced by 56, 23, 60 and 54 days respectively in the Père David's deer. The times of onset and termination of the breeding season of Père David's deer were also significantly advanced by 90 days, but in both species, the breeding season was of similar duration (160 ± 5 (s.e.m.) days). Changes in liveweight of adult red deer could be explained by changes in VFI rather than efficiency of utilization. This was not the case in Père David's deer and may indicate seasonal changes in the efficiency of energy utilization. In order to establish whether these species differences develop with age, we undertook a second study in which seasonal changes in VFI, growth, plasma prolactin concentrations and the timing of the onset of the breeding season were recorded for ten red deer and six Père David's deer from 6 to 18 months of age. Both species exhibited a similar decline in VFI in the first autumn of life. Subsequently, the Père David's deer exhibited an advance in the timing of the seasonal peak in VFI and prolactin (21 and 66 days respectively); puberty occurred 3 months earlier than in red deer. The earlier breeding season of the Père David's deer was associated with a significant advance in a range of seasonal endocrine and physiological parameters. These species differences may develop with age. Our data indicate that seasonal patterns of metabolism and growth may be closely linked to those mechanisms which also regulate the onset and termination of the breeding season.
Journal of Endocrinology (1989) 122, 733–745
