The properties of nuclear receptors belonging to the superfamily of receptors acting as transcription factors are modulated by nutritional and hormonal conditions. We showed recently that retinoic acid (RA) restored to normal the expression of receptors attenuated by hypothyroidism. The present study was designed to find out whether dietary vitamin A (as retinol) had the same effect. Propylthiouracil in drinking water induced both hypothyroidism and a vitamin A-deficient status in rats. The maximum binding capacity (CmJ of triiodothyronine nuclear receptors (TR) was unchanged, while that of nuclear RA receptors (RAR) and nuclear glucocorticoid hormone receptors (GR,) was reduced in the liver of these hypothyroid rats. The reduced C,,, of RAR stemmed from a lower level of RAR mRNA, while the reduced C , , , of GR, was assumed to be due to reduced translocation of the receptor from the cytosol to the nucleus. Feeding the hypothyroid rats with a vitamin A-rich diet did not restore the C,,, of either RAR or G& to normal. The lack of effect of dietary retinol on RAR expression may be attributed to either genomic (unoccupied T R block the expression of RAR genes) and/or extragenomic (hypothyroidism decreases the availability of retinol and/or its metabolism to RA) mechanisms. Triiodothyronine is thought to favour the translocation of glucocorticoid hormone receptors from cytosol to nucleus. These findings provide more information on the relationship between vitamin A and hormonal status, showing that a vitamin A-rich diet is without apparent effect on the expression of nuclear receptors in hypothyroid rats.

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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-iodothyromne receptors (TR) while the expression of retinoic acid (RA) receptors (RAR) was unaffected. After 10 months of alcoholizatton 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 mvolved 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), (11) the increased expression of RAR could induce apoptosis and subsequently liver necrosis.

Rctinoic acid (RA) and triiodothyronine (T,) exert many of their actions by binding to specific nuclear receptors (respectively, RA receptor (RAR) and T,) receptor (TR) belonging to a 'superfamily of receptors. Some hetcrologous regulation of those receptors has been shown, and in particular regulation of the maximum binding capacity of TR by either rctinol or RA. Now, using hyprthyroidic rats as a model, the effect of RA on binding capacity and on the mRNA levels of TR and RAR wits investigated. The resulls show that the benefit of vitamin A treatment for the hyprthyroidic state, w/hi& has been described for a long time, could be the result of a down.heteroregulation of TR by RA, the active metabolite of rcdnol.