Abstract

This project is designed to continue the study of the similarities and differences in the interaction of estrogens and antiestrogens with uterine tissue, and in particular, to distinguish the subcellular site or sites where estrogens and antiestrogens exhibit clearly differing actions. This subcellular site(s) may then be the point at which antiestrogens inhibit any further estrogenic response. In order to determine why the initial interaction of estrogens versus antiestrogens with the cytoplasmic estrogen receptor and the subsequent formation of the nuclear estrogen receptor results in differential nuclear binding, the interaction of these receptor complexes to the acceptor--effector site(s) on chromatin will be investigated. This will be done by studying the receptor complex binding to isolated and purified chromatin subfractions. Such studies will require the synthesis of radiolabeled high affinity antiestrogens. Structural differences between the estrogen and antiestrogen receptor complexes (cytoplasmic or nuclear) will be studied primarily by gel filtration and ion exchange chromatography. In addition to using 3H-labeled estrogens or antiestrogens, the receptor itself will be radiolabeled. Consideration will be given to the nature of the in vivo salt-extractable versus salt-resistant nuclear binding of antiestrogens and estrogens and the relationship of such binding to the """"""""fallout"""""""" and recycling of the nuclear estrogen receptor.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
3R01HD013425-06S1
Application #
3312196
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1979-07-01
Project End
1985-09-30
Budget Start
1984-07-01
Budget End
1985-09-30
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Saint Louis University
Department
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63103

  Publications

Ruh, M F; Dunn 2nd, R; Ruh, T S (1996) Interrelationships between nuclear structure and ligand-activated intracellular receptors. Crit Rev Eukaryot Gene Expr 6:271-83
Ruh, M F; Cox, L K; Ruh, T S (1996) Estrogen receptor interaction with specific histones. Binding to genomic DNA and an estrogen response element. Biochem Pharmacol 52:869-78
Dunn 2nd, R T; Ruh, T S; Burroughs, L K et al. (1996) Purification and characterization of an Ah receptor binding factor in chromatin. Biochem Pharmacol 51:437-45
Dunn 2nd, R T; Ruh, T S; Ruh, M F (1993) Binding of the Ah receptor to receptor binding factors in chromatin. Biochem Pharmacol 45:1121-8
Turner, J W; Ruh, M F; Ward, D T et al. (1991) Effects of antiestrogen versus antiprogestin on transformed and nontransformed steroid receptors. J Steroid Biochem Mol Biol 38:197-203
Ruh, M F; Turner, J W; Paulson, C M et al. (1990) Differences in the form of the salt-transformed estrogen receptor when bound by estrogen versus antiestrogen. J Steroid Biochem 36:509-16
Singh, R K; Ruh, M F; Butler, W B et al. (1986) Acceptor sites on chromatin for receptor bound by estrogen versus antiestrogen in antiestrogen-sensitive and -resistant MCF-7 cells. Endocrinology 118:1087-95
Ruh, M F; Singh, R K; Mak, P et al. (1986) Tissue and species specificity of unmasked nuclear acceptor sites for the estrogen receptor of Squalus testes. Endocrinology 118:811-8
Shyamala, G; Singh, R K; Ruh, M F et al. (1986) Relationships between mammary estrogen receptor and estrogenic sensitivity. II. Binding of cytoplasmic receptor to chromatin. Endocrinology 119:819-26
Sheen, Y Y; Ruh, T S; Mangel, W F et al. (1985) Antiestrogenic potency and binding characteristics of the triphenylethylene H1285 in MCF-7 human breast cancer cells. Cancer Res 45:4192-9

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