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An Endogenous Ligand for Type II Binding Sites in Normal and Neoplastic Tissues

  • James H. Clark
  • Barry M. Markaverich
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 196)

Abstract

The rat uterus contains two classes of specific nuclear estrogen binding sites which may be involved in estrogen action. Type I sites represent the classic estrogen receptor (Kd 1 nM) and type II sites (Kd 10–20 nM) are stimulated in the nucleus by estrogen under conditions which cause uterine hyperplasia. Dilution of uterine nuclear fractions from estrogen treated rats prior to quantitation of estrogen binding sites by [3H]-estradiol exchange results in an increase (3–4 fold) in the measurable quantities of the type II site. Estimates of type I sites are not affected by dilution. These increases in type II sites following nuclear dilution occur independently of protein concentration and result from the dilution of a specific endogenous inhibitor of [3H]-estradiol binding to these sites. The inhibitor activity is present in cytosol preparations from rat uterus, spleen, diaphragm, skeletal muscle and serum. Preliminary characterization of the inhibitor activity by Sephadex G-25 chromatography shows two distinct peaks which are similar in molecular weight (300). These components (α and β) can be separated on LH-20 chromatography since the β-peak component is preferentially retained on this lipophilic resin. Partial purification of the LH-20-β inhibitor component by high performance liquid chromatography and gas-liquid chromatographymass spectrometric analysis suggest the putative inhibitor activity is not steroidal in nature and consists of two very similar phenanthrene-like molecules (molecular weights 302 and 304). Analysis of cytosol preparations on LH-20 chromatography shows that non-neoplastic tissues (uterus, liver, lactating mammary gland) contain both α and β inhibitor components whereas estrogen-induced rat mammary tumors contain very low to non-measurable quantities of the β-peak inhibitor activity.

Keywords

Inhibitor Component Nuclear Type Putative Inhibitor Cytosol Preparation Estradiol Binding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • James H. Clark
    • 1
  • Barry M. Markaverich
    • 1
  1. 1.Department of Cell BiologyBaylor College of MedicineHoustonUSA

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