LIGANDS OF 4 RECEPTORS IN THE NUCLEAR STEROID THYROID HORMONE SUPERFAMILY INHIBIT INDUCTION OF RAT CYTOSOLIC ALDEHYDE DEHYDROGENASE-3 (ALDH3C) BY 3-METHYLCHOLANTHRENE/

Using six ligands that bind to four different receptors in the nuclear steroid/thyroid hormone superfamily, we have examined the effects of these chemicals on induction of the cytosolic aldehyde dehydrogenase ( ALDH3c) activity by 3-methylcholanthrene (3MC) in rat liver and uterus . Tn contrast to negligible activities in the untreated rat, ALDH3c en zyme activities are induced after a single dose of 3MC. Hepatic ALDH3c induction is decreased 60% to 90% when 3MC is administered together w ith any of the following ligands: estradiol, testosterone, progesteron e, hydrocortisol, diethylstilbestrol, or tamoxifen. None of these same doses of chemicals, administered alone, affects ALDH3c enzyme activit y. In addition, when these ligands are injected 2 days after 3MC, no c hanges are observed in liver or uterus ALDH3c induction. These results suggest that ligands that bind to different receptors in the nuclear steroid/thyroid hormone superfamily might inhibit the ALDH3c induction process by polycyclic aromatic hydrocarbons; the molecular mechanism( s) of this inhibitory effect is not yet understood.