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Plasma corticosterone clearance in anaesthetized rats was measured from the disappearance of radioactivity after a bolus injection of [3~corticosterone. Mean fractional clearance rates were significantly (P < 0.05) reduced after a 48 h fast, by 32 and 22% for males and females respectively.Plasma corticosterone concentrations were increased by fasting in both sexes. Corticosterone secretion rates, calculated as the product of fractional clearance and plasma corticosterone concentration, did not differ between fed and fasted groups in either sex. The mean activity (U/liver) of the rate-limiting enzyme for corticosterone degradation, hepatic 4,5-dihydrocorticosterone :NADP+ A4-oxidoreductase, was significantly reduced by 51 and 78 % after fasting in males and females respectively. This was due to changes in both the soluble and microsomal forms of the enzyme. The binding capacity of corticosterone-binding globulin in plasma was significantly reduced by fasting in females (P < 0.001), but was not altered in males. The results suggest that reduced hormone clearance is the dominant cause of fasting hypercorticosteronaemia in the rat. Fasting: Corticosterone metabolism: RatCorticosteroids play a major role in the metabolic response to undernutrition, by causing increased release of amino acids from skeletal muscle, and their subsequent conversion to glucose in the liver (Waterlow et al. 1978;Munck et al. 1984;Tischler et al. 1988). Plasma corticosteroid concentration is generally assumed to be controlled by pituitary release of adrenocorticotrophin, which increases adrenal steroid secretion. Thus, increased levels of plasma adrenocorticotrophin and corticosteroids have been found in fasted humans (Beer et a/. 1989) and in cockerels given a diet deficient in protein (Carsia et al. 1988).The capacity of the liver to catabolize corticosterone is, however, highly dependent on the level of food consumption (Herbst et al. 1960). Since this organ is the major site of corticosteroid metabolism (Norman & Litwack, 1987), a decreased ability to catabolize corticosterone might increase plasma steroid levels independently of changes in adrenal secretion. The aim of the present investigation was to measure the turnover rate of plasma corticosterone, in order to assess the relative contributions of reduced clearance and increased secretion to the raised corticosterone levels found during fasting. In addition, measurements have been made of the binding capacity of plasma corticosterone-binding globulin (CBG), and of the activity of hepatic 4,5-dihydrocorticosterone : NADP+ A4-oxidoreductase (corticosterone reductase), the rate-limiting enzyme for corticosterone degradation. A preliminary report of this work has already been given (Woodward et al. 1990). M A T E R I A L S A N D M E T H O D S AnimalsThe rats were F1 hybrids obtained from our breeding colonies by crossing PVG/C Lister Hooded males with WAG/C Wistar Albino females. Three experiments were carried out.https://www.cambridge.org/core/terms. https://doi

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