The effect of vitamin A supplementation on stearoyl-CoA desaturase gene 1 expression in mouse liver was characterized. Normal BALB/c mice were fed 0.01% and 0.1% retinol palmitate as components of nonpurified diets. This treatment resulted in a 3-fold and a 7-fold induction of SCD1 mRNA levels, respectively, as determined by RNase protection analysis, Vitamin A-deficient animals were also fed diets containing 0.01% and 0.1% retinol palmitate, resulting in a similar pattern, of SCD 1 mRNA induction. Fatty acid synthase and beta-actin mRNA levels did not respond consistently or significantly to retinoic acid treatment. Dietary and hormonal studies were carried out to investigate the role of the retinoid X receptor in the regulation of SCD1 by type II steroid hormones, A receptor-saturating dose of thyroid hormone, triiodothyronine, repressed vitamin A-elevated SCD1 mRNA levels in vivo. Peroxisome proliferator-elevated SCD1 mRNA levels were unaffected by administration of thyroid hormone. This suggests that the retinoic acid receptor transcriptionally regulates SCD1 through a traditional mechanism of heterodimerization with the retinoid X receptor, (C) 1997 Academic Press.