Identification and characterization of membrane estrogen receptor from MCF7 estrogen-target cells

2001 ◽  
Vol 77 (2-3) ◽  
pp. 97-108 ◽  
Author(s):  
Charles E. Powell ◽  
Ana M. Soto ◽  
Carlos Sonnenschein
Endocrinology ◽  
2002 ◽  
Vol 143 (8) ◽  
pp. 3071-3082 ◽  
Author(s):  
Ganesan Sathya ◽  
Michelle S. Jansen ◽  
Susan C. Nagel ◽  
C. Edgar Cook ◽  
Donald P. McDonnell

Abstract The steroid hormones estrogen and progesterone together regulate the development and maintenance of the female reproductive system. The actions of these two hormones are mediated by their respective nuclear receptors located within overlapping cell populations in target organs. The molecular mechanism of action of these two hormones has been defined to a large extent using estrogen receptor (ER) and progesterone receptor (PR) antagonists. In the case of ER, the available antagonists are highly receptor selective. With respect to PR, however, the available antiprogestins also interact with the receptors for glucocorticoids, mineralocorticoids, and androgens. Whereas these cross-reactivities can usually be managed in studies of female reproductive function, it is the recent demonstration that RU486 is an effective antagonist of the β-isoform of ER that suggested the need for more selective antiprogestins. In this study, we used cell-based transcriptional assays combined with screens using coactivator peptide analogs to identify two novel classes of antiprogestins that distinguish themselves from the antiprogestin RU486 in the manner they interact with PR. One class exhibits the characteristics of a pure antiprogestin in that its members bind to the receptor and induce a conformational change that prevents the presentation of two potential coactivator binding surfaces on the protein. The second class of compounds distinguish themselves from RU486 in that they are ERβ sparing. When tested in vivo the ER-sparing antiprogestins were as effective as RU486 in suppressing superovulation. It is anticipated that the availability of these new antiprogestins will advance the studies of PR pharmacology in a manner similar to how the availability of selective ER modulators has helped the study of ER action.


2010 ◽  
Vol 315 (1-2) ◽  
pp. 314-318 ◽  
Author(s):  
Mukesh K. Gandhari ◽  
Chester R. Frazier ◽  
Julia S. Hartenstein ◽  
Jean-Francois Cloix ◽  
Michel Bernier ◽  
...  

2000 ◽  
Vol 68 (6) ◽  
pp. 3269-3274 ◽  
Author(s):  
Celio L. Silva ◽  
Douglas B. Lowrie

ABSTRACT As we seek to develop and evaluate new vaccines against tuberculosis, it is desirable that we understand the mechanisms of protective immunity in our models. Adoptive transfer of protection with hsp65-specific T-cell clones from infected or vaccinated mice into naı̈ve mice had indicated that cytotoxic T cells can make a major contribution to protection. We characterized 28 CD4+CD8− and 28 CD4− CD8+hsp65-specific T-cell clones derived from infected or vaccinated mice. Half of the CD4+ CD8− and 64% of the CD4− CD8+ clones were cytotoxic. Cytotoxicity was associated with high expression of CD44 and gamma interferon production. Most (86%) of the cytotoxic CD4+CD8− clones lysed target cells via the Fas-FasL pathway, and most (83%) of the cytotoxic CD4− CD8+clones lysed target cells via cytotoxic granules. Only the clones using the granule-mediated pathway caused substantial loss of viability of virulent Mycobacterium tuberculosis during lysis of infected macrophages, and the degree of killing closely correlated with the availability of granule marker enzyme activity. Granule-mediated cytotoxicity thus may have a key role in protection against tuberculosis by delivering mycobactericidal granule contents.


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