Ligands of four 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. In contrast to negligible activities in the untreated rat, ALDH3c enzyme activities are induced after a single dose of 3MC. Hepatic ALDH3c induction is decreased 60% to 90% when 3MC is administered together with any of the following ligands: estradiol, testosterone, progesterone, hydrocortisol, diethylstilbestrol, or tamoxifen. None of these same doses of chemicals, administered alone, affects ALDH3c enzyme activity. In addition, when these ligands are injected 2 days after 3MC, no changes 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 ALD3H3c induction process by polycyclic aromatic hydrocarbons; the molecular mechanism(s) of this inhibitory effect is not yet understood.
Karageorgou
M
M
Department of Pharmacology, University of Ioannina Medical School, Greece.
Vasiliou
V
V
Nebert
D W
DW
Marselos
M
M
D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism
D002273:Carcinogens; D006728:Hormones; D018336:Receptors, Aryl Hydrocarbon; D011956:Receptors, Cell Surface; D008748:Methylcholanthrene; D000444:Aldehyde Dehydrogenase