Accession Number:

ADA301696

Title:

Regulation of the Estrogen Receptor Structural Gene in Breast Tissue by the AH Receptor.

Descriptive Note:

Annual rept. 1 Aug 94-31 Jul 95,

Corporate Author:

ROCHESTER UNIV NY SCHOOL OF MEDICINE AND DENTISTRY

Personal Author(s):

Report Date:

1995-08-29

Pagination or Media Count:

12.0

Abstract:

The Ah receptor AhR, a gene regulatory protein, has been implicated to play a significant role in the development andor progression of mammary tumors in humans and animals. We further hypothesize that it plays a role in the normal development of breast tissue. We will define the cell- and developmentally-related expression and activation of the AhR in mammary tissue, determine the ability of AhR agonists to affect the expression of the estrogen receptor ER in this tissue, and define the mechanisms by which these events occur. We have shown that the human ER structural gene contains specific DNA sequences that binds activated human AhR under conditions in vitro. We have sought to establish an in vivo model to further investigate the mechanisms whereby the AhR may regulate the ER gene. In contrast to previous investigations by others, we found that the AhR agonist, TCDD, did not affect either ER levels or estrogen-induced responses in the weanling female rat. These data indicate that age andor developmental period play a crucial role in the ability of TCDD, via the AhR, to modulated the ER and estrogen-mediated responses. We are progressing on proposed studies to examine the developmental expression of the MIR in rat mammary tissue and the effects of AhR agonists on ER expression. We have also determined that a gene encoding an enzyme intimately involved in steroid hormone metabolism, 3B-hydroxysteroid dehydrogenase isomerase, is affected by AhR agonists. We will further examine the regulation of this gene in breast tissue.

Subject Categories:

  • Medicine and Medical Research
  • Toxicology
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE