1. Sponsor Organization: NIH/NIEHS

2. Project Title: 04244-12 TOXIC CHEMICALS EFFECTS ON FETAL ADRENAL AND LIVER

3. Project Focus:

• Project Primary Focus: Human Health Effects
• Project Secondary Focus:

4. Description:

The adrenal steroid products, glucocorticoids, appear to play an important role in the expression of hepatic cytochrome P-450 dependent monooxygenases and other enzymes involved in metabolism of foreign compounds, such as glutathione S-transferase and NAD(P)H:quinone oxidoreductase. We have observed either a potentiation or repression in the induction of several hepatic enzyme activities by polycyclic aromatic hydrocarbons (PAH) in the presence of glucocorticoids, suggesting a cooperative modulation of Ah receptor action by the glucocorticoid receptor. The effects of glucocorticoids on the expression of hepatic onooxygenases and other enzymes in hepatocyte cell culture will be measured by enzyme assay, by immunoblotting techniques for enzyme protein, and by measurements of the levels and rates of synthesis of mRNA specific for these enzymes with Northern analyses. A second specific aim will address the role of protein phosphorylation on the Ah and ARE receptor function in the absence and presence of glucocorticoids. A battery of genes under the control of either the Ah or Antioxidant Response receptors will be tested for their dependence on protein kinase action for induction. A third Specific Aim involves use of adrenalectomized animals to ascertain whether lack of adrenal steroids diminishes induction of these enzymes by PAH or t-butylhydroquinone in vivo. A final Specific Aim would address whether there are protein-protein interactions between the two receptors when the glucocortoid receptor positively interacts with the Ah receptor.

5. References:

6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary:
• Secondary:
  • Basic Research

8. Keywords for Experimental System/Species:

• Species:
• Study Type:
  • In Vivo
  • Laboratory Study
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
• Hormonal Measures:
  • Adrenal Hormones
  • Ah Receptor
• Level Of Study:
  • Enzymology
  • Molecular
• Chemistry Metabolism:
  • Cytochrome P450
• Life Stage:
• Risk Assessment:

10. Chemical Agents:

• Pahs
• T-Butylhydroquinone

11. Performing Institution:

• UNIVERSITY OF LOUISVILLE

12. Contact:

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