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  • Author: D. J. Millward x
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D. J. Millward, J. G. Brown and J. van Bueren

ABSTRACT

To examine whether the low plasma levels of triiodothyronine (T3) in fasted rats might limit the recovery of muscle protein synthesis on refeeding, rats were fasted for either 3 or 4 days and refed with or without pretreatment with thyroid hormones. Fasting suppressed T3 levels, plasma insulin and the rate of the translational phase of muscle protein synthesis (K RNA; the rate per unit RNA), especially after the 4-day fast. On refeeding, plasma T3 levels remained low for more than 3 h after the 3-day fast and for more than 8 h after the 4-day fast. Insulin concentrations increased within the first hour of refeeding, eventually achieving supranormal concentrations after the 3-day fast. The K RNA increased within the first hour of refeeding, achieving well-fed control values by 3 h after the 3-day fast or 24 h after the 4-day fast. The increases in K RNA were significantly correlated with the increases in insulin at low insulin concentrations, achieving a plateau value at 150 pmol/l, so that further increases in insulin were not associated with any further increases in protein synthesis. Pretreatment with thyroid hormone induced increased T3 levels which were maintained for up to 8 h of refeeding. This had no effect on the responses of either insulin or protein synthesis to refeeding after the 3-day fast, but did result in an acceleration of the recovery in the K RNA and plasma insulin levels in the rats fasted for 4 days. Analysis of the insulin–K RNA relationship showed no evidence for any increase in the insulin sensitivity of muscle protein synthesis with thyroid pretreatment, the initial stimulation of protein synthesis on refeeding the rats fasted for 4 days reflecting increased insulin secretion. Since in the untreated animals, insulin secretion on refeeding was also correlated with T3 levels, these results are consistent with the previously reported thyroidal dependence of insulin secretion.

J. Endocr. (1988) 118, 417–422

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Z. A. H. Yahya, P. C. Bates and D. J. Millward

ABSTRACT

The relative biological importance of plasma levels of insulin-like growth factors (IGFs) is uncertain since the IGFs may act through endocrine mechanisms involving circulating IGFs secreted by the liver, or by autocrine/paracrine mechanisms with IGF production in or close to their target cells. We report here studies in rats designed to examine this problem with an investigation of the changes in plasma and tissue concentrations of IGF-I in relation to the inhibition of bone and muscle growth and proteoglycan synthesis, a putative IGF-I-sensitive process, by protein deficiency. Over a 3-week period in young well-fed growing rats, there were marked increases in plasma IGF-I, whereas in the protein-deficient animals in which growth was inhibited concentrations fell markedly. In bone, concentrations of IGF-I were initially 20% of plasma, did not increase with age and were minimally influenced by protein deficiency. In skeletal muscle, concentrations of IGF-I were initially 3% of plasma, did not increase with age, but did fall with protein deficiency. In bone, the inhibition of proteoglycan synthesis by the protein deficiency was not correlated with changes in tissue IGF-I concentrations and was poorly correlated with changes in plasma hormone concentrations, although in the latter case an exponential relationship could be fitted to the data from the initial control and subsequent protein-deficient animals. In muscle, the changes in proteoglycan synthesis were significantly linearly correlated with changes in tissue IGF-I compared with an exponential relationship with plasma concentrations from the initial control and subsequent protein-deficient animals. These data demonstrate that neither plasma IGF-I concentrations nor the level of total extractable tissue IGF-I can be assumed to be unequivocal determinants of IGF-I status.

Journal of Endocrinology (1990) 127, 497–503

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P. C. Bates, L. F. Chew and D. J. Millward

ABSTRACT

The effects of the anabolic steroid stanozolol on whole body and muscle growth and protein metabolism in the rat have been examined. No responses could be found in normal well-fed male rats. Female rats responded to 1 mg/kg per day with an increased body and skeletal muscle growth rate and an increase in muscle protein synthesis. The anabolic action on muscle protein synthesis was due to increased RNA concentration with no change in the rate of protein synthesis per unit RNA (K RNA). Investigation of any anticatabolic effects of stanozolol treatment in male rats deprived of food for 24 h indicated no response of protein balance and turnover. However, rats treated with catabolic doses of corticosterone (50 mg/kg per day) did respond to stanozolol with decreased muscle growth inhibition due to better-maintained muscle protein synthesis. The latter response was due to a reversal of the corticosterone-induced reduction of K RNA, but with no effect on RNA concentration. Thus there appear to be at least two effects of stanozolol; an anabolic action evident only in female rats, involving increased muscle RNA concentrations, and an anticatabolic action involving inhibition of the corticosterone-induced fall in muscle RNA activity. In both cases, stanozolol influenced muscle protein synthesis with no evident effects on protein degradation.

J. Endocr. (1987) 114, 373–381

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P. C. Bates, P. T. Loughna, J. M. Pell, D. Schulster and D. J. Millward

ABSTRACT

Hypophysectomy of adult rats results in a loss of body growth which can be reversed by treatment with GH. The increased growth caused by administration of GH is accompanied by an increase in food consumption. The effects of GH and interactions with nutrition were investigated by treating hypophysectomized rats with GH and either providing unrestricted food or preventing the increased food consumption by pair-feeding with the same intake as that of the hypophysectomized animals.

Over the 7-day experimental period, the GH-treated animals grew significantly when food was available ad libitum but did not gain body weight when an increase in food intake was prevented. However, there was a significant interaction between GH and nutrition on body composition; GH significantly decreased body fat and increased the protein: fat ratio only in the animals with the restricted intake. Gastrocnemius muscle weight was increased by GH regardless of food intake, but heart weight did not increase and liver weight was actually decreased by GH teatment when food intake was restricted. Serum concentrations of insulin and insulin-like growth factor-I (IGF-I) were increased by GH in the rats with food available ad libitum but not in the pair-fed rats. However, the liver concentration of IGF-I and its mRNA were increased by GH although the increase in IGF-I mRNA was modulated by the restricted food intake. The decreased weight of the liver in the pair-fed GH-treated rats, despite the increase in IGF-I mRNA, suggests that IGF-I does not influence liver growth. In the gastrocnemius muscle, however, GH increased IGF-I mRNA concentration similarly in both rats with food available ad libitum and in pair-fed rats. Decreased nutrition therefore modulated the action of GH but emphasized its nutrient partitioning effect, thus increasing the anabolic drive towards skeletal muscle growth; this appeared to be mediated by the local production of IGF-I within the muscle.

Journal of Endocrinology (1993) 139, 117–126