Exploring the Suitability of a Specifici Glucocorticoid Receptor Antagonist as a Tool in the Study of the Regulation of Rat Lung Alveolarization by Glucocorticoids

• Main Author: Lopez, Ana Sofia
• Other Authors: Sweezey, Neil
• Language: en_ca
• Published: 2010
• Subjects: alveolarization; glucocorticoids; rat lung development; glucocorticoid receptor antagonist; 0719
• Online Access: http://hdl.handle.net/1807/25774

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.