Differential regulation of hepatic enzymes by polycyclic aromatic hydrocarbons and glucocorticoids

Conference · Fri Mar 15 00:00:00 EST 1991 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5239047

Smith, J A; Linder, M W; Fernandez, D; Prough, R A ^[1]

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1. Univ. of Louisville, KY (United States)

A putative glucocorticoid (GC) response element has been identified within the first intron of the P450IA1 gene and is apparently necessary for GC-dependent potentiation of polycyclic aromatic hydrocarbon (PAH) induction of P450IA1. In cultured rat hepatocytes, the synthetic GC, dexamethasone (DEX), potentiated PAH induction of both P450IA1 and glutathione S-transferase protein and mRNA. However, DEX caused a small decrease in PAH-dependent induction of NAD(P)H:quinone oxidoreductase (QOR) subunit protein and mRNA in culture. The potentiation of 3-methylcholanthrene (MC) dependent induction of hepatic P450IA1, GST and QOR by low doses of DEX was evaluated in neonatal and adult rats. In neonates, MC induction was potentiated 2-, 1.5-, and 1.4-fold for P450IA1, GST, and QOR activities, respectively, by DEX. However, in adult rats, DEX potentiated MC induction of P450IA1 activity, but repressed MC induction of GST and QOR. Western immunoanalysis and Northern analysis indicated that the changes in these activities were associated with parallel changes in the levels of immunoreactive proteins and mRNA. Glucocorticoids may have an age-dependent influence on the induction of hepatic enzymes by PAH possibly involving other regulatory factors, in addition to Ah and GC receptors.

• OSTI ID: 5239047
• Report Number(s): CONF-9104107-; CODEN: FAJOE
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 5:5; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
GLUCOCORTICOIDS
BIOCHEMICAL REACTION KINETICS
MIXED-FUNCTION OXIDASES
GENE REGULATION
POLYCYCLIC AROMATIC HYDROCARBONS
BIOLOGICAL EFFECTS
AGE DEPENDENCE
DEXAMETHASONE
ENZYME ACTIVITY
ENZYME INDUCTION
LIVER
MESSENGER-RNA
OXIDOREDUCTASES
RATS
TRANSFERASES
ADRENAL HORMONES
ANIMALS
AROMATICS
BODY
CORTICOSTEROIDS
DIGESTIVE SYSTEM
ENZYMES
GLANDS
HORMONES
HYDROCARBONS
HYDROXY COMPOUNDS
KETONES
KINETICS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXYGENASES
PREGNANES
PROTEINS
REACTION KINETICS
RNA
RODENTS
STEROID HORMONES
STEROIDS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology