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Although adrenalectomy was without effect on the expression of retinoic acid (RA) receptors (RARs), administration of the glucocorticoid analog dexamethasone (Dex) to both control and adrenalectomized rats reduced the expression of these receptors in rat liver. This effect can be mainly attributed to the action of Dex on 4-hydroxylation of RA. Dex, by enhancing 4-hydroxylation of RA, reduces its intracellular concentration thereby leading to a decreased expression of RARs, since RARbeta, the main type of RARs in liver, are known to be up-regulated by RA.

Chronic alcoholism induces perturbations of storage and metabolization of retinol and related compounds. After 6 months of ethanol consumption we have observed in mouse liver an increased expression of Tri-iodothyronine receptors (TR) while the expression of retinoic acid (RA) receptors (RAR) was unaffected. After 10 months of alcoholization the TR expression was strongly increased and the RAR expression was also increased. At this time the activity of aldehyde dehydrogenase and that of alcohol dehydrogenase, two enzymes involved in biosynthesis of RA from retinol, were similar in the liver of alcoholized and pair-fed mice. Thus it can be hypothesized that (i) the change of RAR expression was, at least in part, the result of a change of TR expression (result in agreement with previous data), (ii) the increased expression of RAR could induce apoptosis and subsequently liver necrosis.

Properties of retinoic acid receptors and glucocorticoid receptors of rat liver were influenced by retinol status in a nonsimilar manner. The binding of the retinoic acid receptors which was lowered in vitamin A--deficient animals relative to controls was restored by a single dose (100 micrograms) of retinoic acid; in vitamin A--overloaded animals (40-fold the control intake) the binding was greater than in controls. The binding of the glucocorticoid receptor was higher in vitamin A--deficient rats than in controls and restored by retinoic acid supplementation, but did not differ from controls in the vitamin A--overloaded rats. The cellular actions of glucocorticoid hormone and retinoic acid were investigated by assaying the activity of some related enzymes. The activity of tyrosine aminotransferase reflected glucocorticoid receptor binding in vitamin A--deficient and vitamin A--restored rats. The decreased tyrosine amino transferase activity observed in vitamin A--overloaded rats could be related to the inhibition of expression of tyrosine amino transferase gene by retinoic acid. Alcohol dehydrogenase activity was unaffected or only slightly affected by vitamin A status. The known existence of glucocorticoid hormone- and retinoic acid--sensitive elements in the alcohol dehydrogenase gene could explain such observations. Furthermore, the changes in the binding of retinoic acid receptors and glucocorticoid receptors were often in opposite directions. These results provide new evidence for the mechanisms by which the amount of dietary vitamin A modulates hormonal status.

1. For a period of 24 d rats were given diets containing either casein or pea (Pisum sativum) protein at two different concentrations (180 and 120 g/kg) without or with cysteine or cysteine + methionine supplementation. 2. The effects of these diets on levels of blood and liver reduced glutathione (GSH) and serum thyroid hormones were studied. 3. When compared with the 180 g casein/kg diet, the 120 g casein/kg diet decreased liver GSH and serum thyroid hormone concentrations. These changes were related to dietary cysteine supply since supplementation induced an increase in these variables. 4. When compared with 180 g pea protein/kg diet, the 120 g pea protein/kg diet decreased liver GSH and serum thyroid hormone concentrations. These changes could not be corrected by cysteine or cysteine + methionine supplementation.

1. For a period of 32 d young rats were given a diet containing (g/kg) 220 casein, 120 casein + 1.93 L-cysteine (Cys), or 120 casein. 2. The formation of 3,5,3'-triiodothyronine (T3)-nuclear protein complexes was reduced in rats fed on the Cys-deficient diet. 3. Scatchard analysis showed that decreased formation of T3-nuclear protein complexes was due to a decreased affinity of T3 receptors; this decrease was induced, at least in part, by a reduced glutathione content. 4. In rats fed on the Cys-deficient diet there was an expected decrease in growth but an unexpected increase in the activities of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) (EC 1.1.1.40). It is suggested that this increase is related to an increased oxidized glutathione:reduced glutathione ratio.