Return to search

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, 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.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/25774
Date10 January 2011
CreatorsLopez, Ana Sofia
ContributorsSweezey, Neil
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
Languageen_ca
Detected LanguageEnglish
TypeThesis

Page generated in 0.0023 seconds