Exploring the Suitability of a Specifici Glucocorticoid Receptor Antagonist as a Tool in the Study of the Regulation of Rat Lung Alveolarization by Glucocorticoids
Background: Intracellular glucocorticoid receptors (GRs) mediate the regulation of lung development, including alveolarization, by glucocorticoids (GCs). One potential approach to determining the role of GC-GR signalling in alveolar formation would be by pharmacologic blockade. Hypothesis: CP472555...
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ndltd-TORONTO-oai-tspace.library.utoronto.ca-1807-257742013-04-19T20:00:38ZExploring the Suitability of a Specifici Glucocorticoid Receptor Antagonist as a Tool in the Study of the Regulation of Rat Lung Alveolarization by GlucocorticoidsLopez, Ana Sofiaalveolarizationglucocorticoidsrat lung developmentglucocorticoid receptor antagonist0719Background: Intracellular glucocorticoid receptors (GRs) mediate the regulation of lung development, including alveolarization, by glucocorticoids (GCs). One potential approach to determining the role of GC-GR signalling in alveolar formation would be by pharmacologic blockade. Hypothesis: CP472555, a novel GR antagonist with negligible anti-PR activity, is a suitable tool for the study of GC-GR regulation of rat alveolarization. Design/Methods: CP472555 doses needed to block GR were estimated in vitro in fetal rat lung primary cultures. Postnatally, a variety of doses were administered intraperitoneally over a range of days. Results: During postnatal days (PN)0-PN10, when GC levels are low, CP472555 induced changes consistent with GR agonist activity. While GC levels increase after PN11, animals exposed to CP472555 from PN11-PN21 exhibit changes consistent with anti-GR antagonist activity. Conclusion: CP472555 causes a degree of GR blockade sufficient to permit further pharmacological investigation of the role of endogenous GC-GR signalling at the end of alveolarization.Sweezey, Neil2010-112011-01-10T17:14:32ZNO_RESTRICTION2011-01-10T17:14:32Z2011-01-10T17:14:32ZThesishttp://hdl.handle.net/1807/25774en_ca |
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alveolarization glucocorticoids rat lung development glucocorticoid receptor antagonist 0719 |
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alveolarization glucocorticoids rat lung development glucocorticoid receptor antagonist 0719 Lopez, Ana Sofia Exploring the Suitability of a Specifici Glucocorticoid Receptor Antagonist as a Tool in the Study of the Regulation of Rat Lung Alveolarization by Glucocorticoids |
description |
Background: Intracellular glucocorticoid receptors (GRs) mediate the regulation of lung development, including alveolarization, by glucocorticoids (GCs). One potential approach to determining the role of GC-GR signalling in alveolar formation would be by pharmacologic blockade.
Hypothesis: CP472555, a novel GR antagonist with negligible anti-PR activity, is a suitable tool for the study of GC-GR regulation of rat alveolarization.
Design/Methods: CP472555 doses needed to block GR were estimated in vitro in fetal rat lung primary cultures. Postnatally, a variety of doses were administered intraperitoneally over a range of days.
Results: During postnatal days (PN)0-PN10, when GC levels are low, CP472555 induced changes consistent with GR agonist activity. While GC levels increase after PN11, animals exposed to CP472555 from PN11-PN21 exhibit changes consistent with anti-GR antagonist activity.
Conclusion: CP472555 causes a degree of GR blockade sufficient to permit further pharmacological investigation of the role of endogenous GC-GR signalling at the end of alveolarization. |
author2 |
Sweezey, Neil |
author_facet |
Sweezey, Neil Lopez, Ana Sofia |
author |
Lopez, Ana Sofia |
author_sort |
Lopez, Ana Sofia |
title |
Exploring the Suitability of a Specifici Glucocorticoid Receptor Antagonist as a Tool in the Study of the Regulation of Rat Lung Alveolarization by Glucocorticoids |
title_short |
Exploring the Suitability of a Specifici Glucocorticoid Receptor Antagonist as a Tool in the Study of the Regulation of Rat Lung Alveolarization by Glucocorticoids |
title_full |
Exploring the Suitability of a Specifici Glucocorticoid Receptor Antagonist as a Tool in the Study of the Regulation of Rat Lung Alveolarization by Glucocorticoids |
title_fullStr |
Exploring the Suitability of a Specifici Glucocorticoid Receptor Antagonist as a Tool in the Study of the Regulation of Rat Lung Alveolarization by Glucocorticoids |
title_full_unstemmed |
Exploring the Suitability of a Specifici Glucocorticoid Receptor Antagonist as a Tool in the Study of the Regulation of Rat Lung Alveolarization by Glucocorticoids |
title_sort |
exploring the suitability of a specifici glucocorticoid receptor antagonist as a tool in the study of the regulation of rat lung alveolarization by glucocorticoids |
publishDate |
2010 |
url |
http://hdl.handle.net/1807/25774 |
work_keys_str_mv |
AT lopezanasofia exploringthesuitabilityofaspecificiglucocorticoidreceptorantagonistasatoolinthestudyoftheregulationofratlungalveolarizationbyglucocorticoids |
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