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M J Dauncey

Publications and source records attributed to M J Dauncey.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effect of thyroid status in the perinatal period on oxidative capacities and mitochondrial respiration in porcine liver and skeletal muscle.

Regulatory thermogenesis is reduced in newborn piglets which have been made hypothyroid during late gestation by giving the sow a high glucosinolate rapeseed diet (test animals). Thereafter, the progressive increase in thermogenic capacity parallels the development of a marked postnatal hyperthyroid state. To explain these effects of thyroid hormones at the tissue and mitochondrial levels, we have examined both liver and skeletal muscle to determine possible underlying changes in (i) tissue oxidative capacities (cytochrome oxidase (CO) activity), between 80 d of gestation and 48 h after birth, and (ii) mitochondrial content and respiratory capacities at 24 h of life. In control piglets, CO activity increased sharply during late gestation and the first 2 d of life in liver and rhomboideus (RH) muscle (P < 0.01), whereas only a prenatal increase was observed in longissimus dorsi (LD) muscle. Test fetuses were hypothyroid and had lower CO activities than controls during late gestation in RH muscle (P < 0.06, at 110 d of gestation; P < 0.08, at birth) and in liver (P < 0.001, at birth). The postnatal increase in CO activity in RH muscle and liver was higher (P < 0.05) in test than in control piglets, and as a result the difference between the 2 groups was not significant by 24-48 h of life. There was no effect of treatment on LD muscle. At 24 h, hyperthyroid test piglets had lower amounts of mitochondrial proteins than controls (P < 0.05) in all three tissues, possibly reflecting reduced mitochondrial protein synthesis during fetal life and suggesting that high postnatal T3 levels did not bring about major increases in protein synthesis within 24 h. However, test piglets exhibited higher rates of mitochondrial respiration than controls in liver and RH muscle, as shown by increases in State III and FCCP-stimulated respirations (P < 0.05), and mitochondrial CO and creatine kinase activities (P < 0.05). In RH muscle, both subsarcolemmal and intermyofibrillar mitochondria showed the same trends. No changes were observed in LD muscle. Our results describe for the first time the effect of thyroid hormones on perinatal oxidative capacities and neonatal mitochondrial respiration in liver and skeletal muscle of the pig, through both the short-term regulation of mitochondrial respiration and the long-term control of mitochondrial biogenesis. The differential sensitivity of LD and RH muscles to thyroid hormones is discussed.

Animals↗
PubMed1996

Role of thyroid hormones in early postnatal development of skeletal muscle and its implications for undernutrition.

Energy intake profoundly influences many endocrine axes which in turn play a central role in development. The specific influence of a short period of mild hypothyroidism, similar to that induced by undernutrition, in regulating muscle development has been assessed in a large mammal during early postnatal life. Hypothyroidism was induced by providing methimazole and iopanoic acid in the feed of piglets between 4 and 14 d of age, and controls were pair-fed to the energy intake of their hypothyroid littermates. Thyroid status was evaluated, and myofibre differentiation and cation pump concentrations were then assessed in the following functionally distinct muscles: longissimus dorsi (l. dorsi), soleus and rhomboideus. Reductions in plasma concentrations of thyroxine (T4; 32%, P < 0.01), triiodothyronine (T3; 48%, P < 0.001), free T3 (58%, P < 0.001) and hepatic 5'-monodeiodinase (EC 1.11.1.8) activity (74%, P < 0.001) occurred with treatment. Small, although significant, increases in the proportion of type I slow-twitch oxidative fibres occurred with mild hypothyroidism, in l. dorsi (2%, P < 0.01) and soleus (7%, P < 0.01). Nuclear T3-receptor concentration in l. dorsi of hypothyroid animals compared with controls increased by 46% (P < 0.001), a response that may represent a homeostatic mechanism making muscle more sensitive to low levels of circulating thyroid hormones. Nevertheless, Na+, K(+)-ATPase (EC 3.6.1.37) concentration was reduced by 15-16% in all muscles (l. dorsi P < 0.05, soleus P < 0.001, rhomboideus P < 0.05), and Ca(2+)-ATPase (EC 3.6.1.38) concentration was significantly reduced in the two slow-twitch muscles: by 22% in rhomboideus (P < 0.001) and 23% in soleus (P < 0.05). It is concluded that during early postnatal development of large mammals a period of mild hypothyroidism, comparable with that found during undernutrition, induces changes in myofibre differentiation and a down-regulation of cation pumps in skeletal muscle. Such changes would result in slowness of movement and muscle weakness, and also reduce ATP hydrolysis with a concomitant improvement in energetic efficiency.

Animals↗
PubMed1996

Selective regulation of myofiber differentiation by energy status during postnatal development.

The role of energy status in postnatal regulation of porcine skeletal muscle development has been determined in littermate animals kept for 3-4 wk on a high (H) or low (L) energy intake (H = 2L), at a thermally neutral [26 degrees C (26H and 26L, respectively)] or low [10 degrees C (10H and 10L, respectively)] environmental temperature. A variety of skeletal muscles was assessed at 7 wk of age for changes in myofiber hypertrophy and differentiation. In contrast with findings in adult humans and rats, there was no selective preservation of type I slow-oxidative fiber size during energy restriction. However, differentiation between mature skeletal myosin heavy-chain isoforms was markedly affected by energy status, and in rhomboideus there were particularly striking effects of both nutrition and temperature: proportions of type I fibers from the four groups 26H, 26L, 10H, and 10L were 34 +/- 2, 50 +/- 4, 73 +/- 2, and 72 +/- 3 (P < 0.005 for diet at 26 degrees C; P < 0.001 for temperature). These changes may have been induced by alterations in both thyroid status and contractile activity. They support the hypothesis of a key role for rhomboideus muscle in thermoregulation and demonstrate the plasticity of skeletal muscle differentiation to environmental change during postnatal life.

Animals↗
PubMed1996

Interactive effects of thermal environment and energy intake on thyroid hormone metabolism in newborn pigs.

The aim of the study was to determine the effects of 48-hour cold exposure (25 vs. 34 degrees C), starting at 6 h of age, and energy intake on thyroid hormone plasma levels, hepatic 5'-deiodinase activity and nuclear 3,3',5-triiodothyronine (T3) receptors in newborn pigs. In the cold, piglets were fed either a similar milk intake (C piglets) to the piglets at thermal neutrality (TN piglets) or were given an extra amount of milk to compensate for the increased heat production (C+ piglets). Concentrations of plasma thyroxine (T4) decreased steadily over the 48-hour investigation and were affected neither by ambient temperature nor by energy intake. At the end of 48 h, plasma levels of T3 and liver 5'-deiodinase activity were similar in TN and C+ piglets and higher than in C piglets. The numbers of T3 receptors were greater in the liver from C and C+, as well as in skeletal muscle from C, than from TN piglets. Results of the study suggest that plasma T3, liver 5'-deiodinase and liver nuclear T3 receptors of the newborn pig can be regulated by energy intake and ambient temperature.

Aging↗
PubMed1996

Perinatal ontogeny of porcine growth hormone receptor gene expression is modulated by thyroid status.

The ontogeny of growth hormone receptors (GHR) represents a critical stage in growth and metabolism. We have investigated the perinatal ontogeny of hepatic and skeletal muscle GHR gene expression in piglets, and its modulation by GH and thyroid hormones. Test piglets were rendered hypothyroid in late gestation by feeding the sow a high-glucosinolate rapeseed meal. Plasma and tissue samples were obtained from test and control piglets at various ages between 80 days of fetal life (80F) and 2 days postnatally. Plasma hormone levels were determined by radioimmunoassay and GHR mRNA by RNase protection assays. In controls, plasma thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels increased between 80F and birth and the early postnatal period was characterized by a marked surge in plasma T3. Test piglets were hypothyroid at 110F with total T4, total T3 and free T3 levels being reduced by 28, 53 and 33% respectively. By contrast, the postnatal increase in T3 was more marked in test than in control animals. Plasma GH levels decreased over the perinatal period and there was no effect of treatment. Hepatic GHR mRNA was at the lower limit of detection at 80F but by 110F was expressed in both groups of animals. However, fetal hypothyroidism at 110F resulted in a marked 70% decrease in hepatic GHR mRNA (p < 0.01). The higher postnatal rise in T3 in test piglets was accompanied by a recovery of hepatic GHR mRNA levels. By contrast with liver, skeletal muscle (longissimus dorsi) expressed high levels of GHR mRNA at 80F and hypothyroidism induced a 68% increase in GHR mRNA (p < 0.001). The present results suggest that thyroid hormones may modulate the perinatal ontogeny of GHR gene expression, in addition to other hormonal factors, and that this modulation is tissue-specific.

Animals↗
PubMed1995

Ouabain sensitive Na+/K(+)-ATPase content is elevated in mdx mice: implications for the regulation of ions in dystrophic muscle.

Recent evidence indicates that in dystrophin-deficient muscle, intracellular sodium content (Na(i)) may be elevated and sodium regulation may be altered or impaired. If there is an elevation in Na(i), this could be due to decreased active pumping of sodium from the cell or increased passive influx of sodium. The present study has therefore determined the content of plasma membrane-bound Na+/K(+)-ATPase in the skeletal muscle of mdx mice; a genetically homologous model of Duchenne muscular dystrophy. Measurements were made on muscles from 5-6-month-old mdx mice and age-matched controls of the C57B1/10ScSn strain (n = 9 pairs), using the vanadate-facilitated ouabain-binding technique. The Na+/K(+)-ATPase concentration per unit weight increased by 2.3-fold in the longissimus dorsi and 1.4-fold in the gastrocnemius of mdx mice compared with controls. The increase in Na+/K(+)-ATPase content is of similar magnitude to the previously reported increase in ouabain-sensitive Na+/K(+)-ATPase activity in mdx muscle, suggesting that this elevated enzyme activity occurs largely through an increase in its concentration. This compensatory increase in the main regulator of internal sodium is likely to occur in an attempt to maintain homeostasis. Nevertheless, the elevated pump concentration is unable to compensate entirely for the increased Na(i). These results are consistent with a previously proposed hypothesis that sodium regulation is abnormal in dystrophin deficient muscles, and also that cell death in these muscles may be due to abnormal regulation of cell volume.

Animals↗
PubMed1995

Cold-induced changes in circulating levels of catecholamines and thyroid hormones are modulated by energy intake in newborn pigs.

Newborn pigs were kept at a low ambient temperature from 6 until 54 h of age and supplied with a limited (LI, 415 g (kg body weight)-1) or a high (HI, 655 g (kg body weight)-1) intake of milk. At the end of the treatment, both groups had similar deep body temperatures and metabolic rates. However, plasma adrenaline and noradrenaline levels were, respectively, 5.8- and 3.0-fold lower (P < 0.01) in HI than LI piglets, whereas plasma 3,5,3'-triiodothyronine (T3) was 1.5-fold higher (P < 0.01) in HI piglets. It is concluded that the hormonal control of cold-induced thermogenesis is modulated by energy intake, with catecholamines and thyroid hormones acting in a closely related and complementary manner.

Aging↗
PubMed1995

Molecular characterization of a developmentally regulated porcine skeletal myosin heavy chain gene and its 5' regulatory region.

Members of the myosin heavy chain (MyHC) gene family show developmental stage- and spatial-specificity of expression. We report on the characterization and identification of a porcine skeletal fast MyHC gene, including its corresponding 5' end cDNA and 5' regulatory region. This MyHC isoform was found exclusively in skeletal muscles from about the last quarter of gestation through to adulthood. Expression of this isoform was higher postnatally and its spatial distribution resembled a rosette cluster; each with a ring of fast fibres surrounding a central slow fibre. This rosette pattern was absent in the adult diaphragm but about 20% of the fibres continued to express this MyHC isoform. Further in vivo expression studies, in a variety of morphologically and functionally diverse muscles, showed that this particular skeletal MyHC isoform was expressed in fast oxidative-glycolytic fibres, suggesting that it was the equivalent of the fast IIA isoform. Two domains in the upstream regulatory region were found to confer differentiation-specific expression on C2 myotubes (-1007 to -828 and -455 to -101), based on in vitro transient expression assays using the chloramphenicol acetyltransferase (CAT) reporter gene. Interestingly, for high levels of CAT expression to occur, a 3' region, extending from the transcriptional start site to part. of intron 2, must be present in all the DNA constructs used.

Aging↗
PubMed1995

Regulation of porcine skeletal muscle nuclear 3,5,3'-tri-iodothyronine receptor binding capacity by thyroid hormones: modification by energy balance.

Thyroid hormones have been implicated in the regulation of nuclear 3,5,3'-tri-iodothyronine (T3) receptor binding capacity (Bmax) but, despite numerous in vivo and in vitro studies, there is considerable controversy regarding their exact role. Since changes in thyroid status alter energy balance and hence may influence T3 receptor numbers, the effects of chronic hypothyroidism and T4 treatment have been studied in young pigs under conditions of controlled energy intake. Four groups of animals comprising a hypothyroid, a euthyroid and a hyperthyroid group, all on the same level of food intake, and a hyperthyroid group on twice the amount of food were used. After 3 weeks on the treatment regimes, both the hypothyroid animals on the same level of food intake and the hyperthyroid animals on twice the amount of food had significantly increased Bmax values (97% and 137% higher respectively) compared with euthyroid controls. However, there was no difference between controls and the hyperthyroid animals on the same level of food intake. In a second study, the effects of short-term treatment of euthyroid animals with T3 was investigated. Results showed that in two groups of controls that received intravenous saline, those on a higher food intake had higher Bmax values (76% increase). Intravenous T3 administration to animals on a low food intake did not change the receptor numbers. In none of the studies was there any change in the dissociation constant of the receptors as a result of different treatments. It is suggested that, at least in postnatal life, thyroid hormones per se have no significant effect on nuclear T3 receptor numbers in skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Short-term regulation of plasma IGF-I concentration by food intake in young growing pigs.

The short-term regulation of plasma insulin-like growth factor-I (IGF-I) concentration by food intake has been studied in 6-8 week old pigs, both within the thermally neutral zone (26 to 30 degrees C) and at a low (12 degrees C) environmental temperature. In animals at thermal neutrality, the plasma level of IGF-I increased significantly after feeding (p < 0.025 to < 0.01); the average maximum rise of 47% occurred at approximately 12h after the meal. When animals were acclimated to a low temperature and food intake was kept constant in relation to body weight, there was a decline in plasma IGF-I concentrations; values after 2-5 days of cold-acclimation were significantly lower than those before cold exposure (p < 0.05 to < 0.005). This effect of cold on plasma IGF-I was probably mediated by changes in energy balance, due to the increased metabolic demand associated with the low temperature. Animals living in the cold for 14 days, with a low fasting level of plasma IGF-I, showed a marked increase in IGF-I after a large meal; values at 8 or 12 h after food were twice as great as those immediately before or 4 h after feeding (p < 0.05 to < 0.005). It is concluded that in young growing animals, a rapid increase in circulating IGF-I levels can occur in response to food intake, at both thermally neutral and low temperatures, and that the peak in concentration may coincide with the anabolic effects of the meal.

Animals↗
PubMed1994

Nutritional regulation of growth hormone receptor gene expression.

The role of energy intake in regulating growth hormone receptor (GHR) gene expression has been assessed in young growing pigs living at thermal neutrality (26 degrees C) for a 4-wk period. To determine the importance of altering metabolic demand while maintaining food intake constant, littermates were also studied in a cold environment (10 degrees C). Results were tissue-specific: the level of GHR mRNA per unit total RNA in liver was greater on high than low (high = 2 x low) food intake (P < 0.001), whereas in muscle it was elevated on the low compared with the high intake diet (P < 0.02) and also at 10 degrees C compared with 26 degrees C (P < 0.04). When results for GHR mRNA were expressed per unit weight of tissue, only the effects of diet on liver and temperature on muscle remained significant. The changes in hepatic GHR mRNA may have been driven in part by nutritionally induced changes in thyroid status, because both plasma 3,5,3'-triiodothyronine concentration and liver 5'-deiodinase activity were greater on the high than the low intake diet (P < 0.001). Levels of liver GHR mRNA probably had a direct influence on growth of the animals, as they were positively correlated with plasma IGF-I and growth rate (P < 0.001), whereas muscle GHR mRNA may have had a metabolic role when energy supplies were limited.

Animal Nutritional Physiological Phenomena↗
PubMed1994

Differential effects of lipid and carbohydrate on enterocyte lactase activity in newborn piglets.

The influence of enteral feeding in the neonate on lactase-phlorizin hydrolase activity in the small intestine has been determined in newborn piglets fed a series of modified colostra, with a controlled metabolizable energy intake, during the first 31.5 h of life. Striking differences were observed between lactase specific activity in mucosal homogenates and enterocyte lactase activity along the villus axis; compared with newborns, the former decreased after feeding colostrum, whereas the latter increased significantly. When lipid was present in adequate amount, the increase in enterocyte lactase activity occurred when carbohydrate was present as either lactose or galactose. However, when the lipid content of the diet was low, there was a specific effect of carbohydrate composition which was dependent on position along the villus axis: in the lower villus, colostra high in lactose or glucose stimulated an increase in lactase, but there was no such effect with a high galactose intake. It is concluded that colostrum increases enterocyte lactase activity during the first day of life, and that this is dependent on both the nutrient composition of the diet and the position of the enterocytes along the villus.

Animals↗
PubMed1994

Regulation of porcine insulin-like growth factor I and growth hormone receptor mRNA expression by energy status.

Regulation of insulin-like growth factor I (IGF-I) and growth hormone (GH) receptor mRNA in liver and muscle by energy status was assessed in 2-mo-old pigs by altering thermoregulatory demand and energy intake over a 5-wk period to produce a range of plasma IGF-I concentrations from 3.5 +/- 0.7 to 28.9 +/- 6.2 nmol/l. These values were related directly to growth rates (0.06 +/- 0.02 to 0.44 +/- 0.01 kg/day) and total hepatic IGF-I mRNA levels. Increased growth rates were accompanied by an increase in hepatic class 1 and class 2 IGF-I mRNA levels and an increase in the ratio of class 2 to class 1 IGF-I mRNA in liver, suggesting a distinct role for class 2 expression in the endocrine growth response. High levels of class 1 transcripts and a virtual absence of class 2 transcripts characterized all muscle tissues examined, and there was no correlation with plasma IGF-I levels. This suggests that growth promotion in response to increased energy status is regulated via endocrine hepatic IGF-I rather than via a paracrine response. The levels of GH receptor mRNA were positively correlated with overall growth rate (P < 0.005) in liver and negatively correlated (P < 0.05) in muscle, indicating distinct tissue-specific effects of energy status.

Animals↗
PubMed1994

Perinatal ontogeny of porcine nuclear thyroid hormone receptors and its modulation by thyroid status.

Induction of nuclear thyroid hormone receptors (TRs) represents a key point in the control of growth, development, differentiation, and metabolism of most tissues. The influence of thyroid status on the ontogeny of hepatic and skeletal muscle TRs has been investigated in perinatal pigs. Plasma concentrations of total and free 3,5,3'-triiodothyronine (T3) increased markedly from 80 days of fetal life (80 f) to 2 days of postnatal life. Test piglets obtained from sows fed a high glucosinolate rapeseed diet had lower T3 and thyroxine levels than controls at 110 f and showed a higher postnatal surge in T3. Maximal T3 binding capacity (Bmax, pmol T3/mg DNA, means +/- SE) in liver increased from 0.07 +/- 0.01 at 80 f to 0.37 +/- 0.02 at birth and then plateaued. In longissimus dorsi muscle, Bmax values were much higher than in liver and increased from 0.90 +/- 0.02 at 80 f to 1.37 +/- 0.13 at birth and then declined to 1.09 +/- 0.11 at 2 days of age. Long-term fetal hypothyroidism affected the ontogenic profile of both liver and muscle receptors but in opposite directions; Bmax values were reduced in liver but increased in muscle. Postnatally, lower muscle Bmax values occurred in parallel with transient higher levels of circulating T3. Apparent binding affinities were slightly different in liver and muscle during fetal life, and there was an effect of age in muscle. In conclusion, as far as the receptor is concerned, fetal muscle can potentially respond to thyroid hormones much earlier in development than the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Roles of skeletal muscle morphology and activity in determining Na(+)-K(+)-ATPase concentration in young pigs.

It has been demonstrated previously that the Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) concentration (total concentration of [3H]ouabain-binding sites = maximal [3H]ouabain-binding capacity, Bmax) in longissimus dorsi muscle is higher in young pigs living in a cold than in a warm environment, with the effect being even greater in those on a low rather than a high energy intake in the cold. The importance of thyroid status, myofiber type and size, and muscular activity in determining the concentration of Na(+)-K(+)-ATPase has therefore been assessed in longissimus dorsi, semitendinosus, and soleus muscles from 8-wk-old littermate pigs, which had been living 35 or 10 degrees C on either a high or a low energy intake for 3-4 wk. Changes in neither plasma thyroid hormone concentrations nor myofiber type could account for the greater Bmax at 10 vs. 35 degrees C observed in all three muscles; instead, it was possibly related to the greater muscular activity associated with shivering in the cold. More than 50% of the increase in Bmax on the low compared with the high intake in the cold could be attributed to the smaller fiber size and hence greater membrane area in animals on the low intake, and it is concluded that membrane surface area must be assessed in studies of membrane-bound enzymes.

Animals↗
PubMed1994

Nutritional modulation of insulin-like growth factor-I expression in early postnatal piglets.

The roles of intrauterine growth retardation, energy intake, and food composition in determining circulating and hepatic concentrations of IGF-I in early postnatal life have been determined. Intrauterine growth-retarded, small-for-gestational-age piglets were kept at thermal neutrality and fed sow's milk replacement formula to repletion at 6-h intervals between 2 and 14 d of age. When their appropriate-for-gestational-age littermates were pair-fed this intake, there were no significant differences in plasma or hepatic concentrations of IGF-I. Thus, under conditions of controlled food intake, prenatal undernutrition does not affect the postnatal expression of IGF-I. However, when appropriate-for-gestational-age piglets were fed to repletion at 6-h intervals over the 12 d, they had a significantly greater hepatic IGF-I concentration (p < 0.002) and food intake (p < 0.001) than the small-for-gestational-age piglets, indicating a critical role for food intake regulation in catch-up growth. Striking differences in growth rate and IGF-I expression were also found between formula-fed, appropriate-for-gestational-age piglets compared with animals left with the sow. The latter grew much more rapidly (p < 0.0001) and had considerably higher levels of plasma IGF-I (p < 0.0001) despite similar hepatic IGF-I concentrations. Differences in plasma IGF-I may have been caused by the high level of IGF-I in maternal milk, by differences in hepatic synthesis and release, or by altered profiles of IGF binding proteins and hence in altered IGF-I clearance from plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Administration of 3,5,3'-triiodothyronine induces a rapid increase in enterocyte lactase-phlorizin hydrolase activity of young pigs on a low energy intake.

The rapid increase in plasma concentration of 3,5,3'-triiodothyronine (T3) which occurs after feeding may invoke changes in lactase-phlorizin hydrolase (LPH) activity of the small intestine. This hypothesis has been tested in 6-week-old pigs living at thermal neutrality (26 degrees C) on a low level of energy intake. Littermate pairs were infused with either saline or T3 at 30 min intervals over a 6 h period, 18-24 h after the last meal. The activity of LPH in mucosal homogenates increased significantly in test compared with control animals (P < 0.05; T3 37% > saline). This was a specific effect on LPH since there was no effect of T3 on the activity of sucrase-isomaltase. Further, it could not be attributed to changes in intestinal morphology since there were no differences in crypt depth, villus height or villus area between the two groups. Enzyme-cytochemical analysis indicated that administration of T3 increases LPH activity at all points along the villus axis, whereas there is no effect on alpha-glucosidase (combined sucrase-isomaltase and maltase) activities. These results indicate that there is unlikely to be a simple causal relation between the immediate increase in plasma T3 after feeding and the initial decline in LPH activity observed previously in young pigs living in a cold environment. By contrast, the subsequent increase in LPH activity could be under the direct control of the food-induced increase in plasma T3 concentration, and the present results suggest a potential role for T3 as an important short-term homeostatic regulator of LPH in the small intestine.

Animals↗