scholarly journals Making Sense of Cross-Talk between Steroid Hormone Receptors and Intracellular Signaling Pathways: Who Will Have the Last Word?

2004 ◽  
Vol 18 (2) ◽  
pp. 269-278 ◽  
Author(s):  
Carol A. Lange
Keyword(s):  
Signaling Pathways ◽  
Cross Talk ◽  
Intracellular Signaling ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Intracellular Signaling Pathways ◽  
Making Sense

Cross-Talk among Intracellular Signaling Pathways Mediates the Diphenyl Ditelluride Actions on the Hippocampal Cytoskeleton of Young Rats

2011 ◽  
Vol 24 (10) ◽  
pp. 1754-1764 ◽  
Author(s):  
Luana Heimfarth ◽  
Samanta Oliveira Loureiro ◽  
Karina Pires Reis ◽  
Bárbara Ortiz de Lima ◽  
Fernanda Zamboni ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cross Talk ◽  
Intracellular Signaling ◽  
Intracellular Signaling Pathways ◽  
Young Rats ◽  
Diphenyl Ditelluride

The A and B isoforms of the human progesterone receptor operate through distinct signaling pathways within target cells

1994 ◽  
Vol 14 (12) ◽  
pp. 8356-8364
Author(s):  
D X Wen ◽  
Y F Xu ◽  
D E Mais ◽  
M E Goldman ◽  
D P McDonnell
Keyword(s):  
Progesterone Receptor ◽  
Signaling Pathways ◽  
Transcriptional Activity ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Expression Level ◽  
Sex Steroid ◽  
Target Cells ◽  
Human Progesterone Receptor

The biological response to progesterone is mediated by two distinct forms of the human progesterone receptor (hPR-A and hPR-B). In most cell contexts, hPR-B functions as a transcriptional activator of progesterone-responsive genes, whereas hPR-A functions as a transcriptional inhibitor of all steroid hormone receptors. We have created mutations within the carboxyl terminus of hPR which differentially effect the transcriptional activity of hPR-B in a cell- and promoter-specific manner. Analogous mutations, when introduced into hPR-A, have no effect on its ability to inhibit the transcriptional activity of other steroid hormone receptors. The observed differences in the structural requirements for hPR-B and hPR-A function suggest that transcriptional activation and repression by PR are mediated by two separate pathways within the cell. In support of this hypothesis, we have shown that hPR-A mediated repression of human estrogen receptor (hER) transcriptional activity is not dependent on hER expression level but depends largely on the absolute expression level of hPR-A. Thus, it appears that hPR-A inhibits hER transcriptional activity as a consequence of a noncompetitive interaction of hPR-A with either distinct cellular targets or different contact sites on the same target. We propose that hPR-A expression facilitates a ligand-dependent cross-talk among sex steroid receptor signaling pathways within the cell. It is likely, therefore, that alterations in the expression level of hPR-A or its cellular target can have profound effects on the physiological or pharmacological responses to sex steroid hormone receptor ligands.

scholarly journals The A and B isoforms of the human progesterone receptor operate through distinct signaling pathways within target cells.

1994 ◽  
Vol 14 (12) ◽  
pp. 8356-8364 ◽  
Author(s):  
D X Wen ◽  
Y F Xu ◽  
D E Mais ◽  
M E Goldman ◽  
D P McDonnell
Keyword(s):  
Progesterone Receptor ◽  
Signaling Pathways ◽  
Transcriptional Activity ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Expression Level ◽  
Sex Steroid ◽  
Target Cells ◽  
Human Progesterone Receptor

The biological response to progesterone is mediated by two distinct forms of the human progesterone receptor (hPR-A and hPR-B). In most cell contexts, hPR-B functions as a transcriptional activator of progesterone-responsive genes, whereas hPR-A functions as a transcriptional inhibitor of all steroid hormone receptors. We have created mutations within the carboxyl terminus of hPR which differentially effect the transcriptional activity of hPR-B in a cell- and promoter-specific manner. Analogous mutations, when introduced into hPR-A, have no effect on its ability to inhibit the transcriptional activity of other steroid hormone receptors. The observed differences in the structural requirements for hPR-B and hPR-A function suggest that transcriptional activation and repression by PR are mediated by two separate pathways within the cell. In support of this hypothesis, we have shown that hPR-A mediated repression of human estrogen receptor (hER) transcriptional activity is not dependent on hER expression level but depends largely on the absolute expression level of hPR-A. Thus, it appears that hPR-A inhibits hER transcriptional activity as a consequence of a noncompetitive interaction of hPR-A with either distinct cellular targets or different contact sites on the same target. We propose that hPR-A expression facilitates a ligand-dependent cross-talk among sex steroid receptor signaling pathways within the cell. It is likely, therefore, that alterations in the expression level of hPR-A or its cellular target can have profound effects on the physiological or pharmacological responses to sex steroid hormone receptor ligands.

scholarly journals Kinases and protein phosphorylation as regulators of steroid hormone action

2007 ◽  
Vol 5 (1) ◽  
pp. nrs.05005 ◽  
Author(s):  
Nancy L. Weigel ◽  
Nicole L. Moore
Keyword(s):  
Cell Signaling ◽  
Signaling Pathways ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Biological Response ◽  
Good Evidence ◽  
Steroid Hormone Receptors ◽  
Specific Cell ◽  
Phosphorylation Sites ◽  
Cell Signaling Pathways

Although the primary signal for the activation of steroid hormone receptors is binding of hormone, there is increasing evidence that the activities of cell signaling pathways and the phosphorylation status of these transcription factors and their coregulators determine the overall response to the hormone. In some cases, enhanced cell signaling is sufficient to cause activation of receptors in medium depleted of steroids. Steroid receptors are targets for multiple kinases. Many of the phosphorylation sites contain Ser/Thr-Pro motifs implicating proline-directed kinases such as the cyclin-dependent kinases and the mitogen-activated kinases (MAPK) in receptor phosphorylation. Although some sites are constitutively phosphorylated, others are phosphorylated in response to hormone. Still others are only phosphorylated in response to specific cell signaling pathways. Phosphorylation of specific sites has been implicated not only in overall transcriptional activity, but also in nuclear localization, protein stability, and DNA binding. The studies of the roles of phosphorylation in coregulator function are more limited, but it is now well established that many of them are highly phosphorylated and that phosphorylation regulates their function. There is good evidence that some of the phosphorylation sites in the receptors and coregulators are targets of multiple signaling pathways. Individual sites have been associated both with functions that enhance the activity of the receptor, as well as with functions that inhibit activity. Thus, the specific combinations of phosphorylations of the steroid receptor combined with the expression levels and phosphorylation status of coregulators will determine the genes regulated and the biological response.

scholarly journals Inhibitory cross-talk between steroid hormone receptors: differential targeting of estrogen receptor in the repression of its transcriptional activity by agonist- and antagonist-occupied progestin receptors.

1995 ◽  
Vol 15 (4) ◽  
pp. 1847-1857 ◽  
Author(s):  
W L Kraus ◽  
K E Weis ◽  
B S Katzenellenbogen
Keyword(s):  
Estrogen Receptor ◽  
Cross Talk ◽  
Hormone Receptor ◽  
Transcriptional Activity ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Primary Cultures ◽  
Steroid Hormone Receptors ◽  
Expression Vectors ◽  
Steroid Hormone Receptor

Although estrogen receptor (ER) and progestin receptor (PR) are members of different steroid hormone receptor subfamilies, there is considerable biological evidence for cross-talk between the estrogen and progestin hormone-receptor signaling pathways. We have developed a model system to analyze the mechanisms underlying this cross-talk, specifically the repression of ER-mediated transcriptional activity by PR complexed with agonistic or antagonistic ligands. Estrogen- and progestin-responsive reporter vectors containing a variety of promoters were transfected into primary cultures of rat uterine cells and 3T3 mouse fibroblasts with expression vectors for PR (the A and/or B isoforms) as well as ER. Our results demonstrate that both PR isoforms can act as potent ligand-dependent repressors of ER activity. The magnitude of the repression was dependent on the PR isoform (i.e., PR A or PR B), ligand type (i.e., agonist or antagonist), PR levels, and ligand concentration but was unaffected by the ER levels. The promoter context was important in determining both the magnitude and PR isoform specificity of the repression for agonist-occupied PR but not for antagonist-occupied PR. Ligand-occupied PR A was a stronger repressor of ER-mediated transcriptional activity than was ligand-occupied PR B, and antagonist-occupied PR was a more effective repressor than agonist-occupied PR. Mechanistic studies suggest that liganded PR represses ER activity by interfering with its ability to interact productively with the transcriptional machinery, a process known as quenching. The data do not support competitive repression, direct repression, or squelching as the mechanism of PR's inhibitory effect. Experiments with ER mutants demonstrated that the N-terminal portion of ER was required for repression by agonist-occupied PR but not by antagonist-occupied PR. These results, as well as other differences between the two PR-ligand complexes, suggest that they differentially target ER when repressing ER transcriptional activity. These findings underscore the mounting evidence for the importance of interactions between members of the steroid hormone receptor family.

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