Exploring the Suitability of a Specifici Glucocorticoid Receptor Antagonist as a Tool in the Study of the Regulation of Rat Lung Alveolarization by Glucocorticoids
Year: 2010
Type: dissertation
Abstract: 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.\nHypothesis: CP472555, a novel GR antagonist with negligible anti-PR activity, is a suitable tool for the study of GC-GR regulation of rat alveolarization. \nDesign/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.\nResults: 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. \nConclusion: 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.
Source: TSpace (University of Toronto)
Author: Ana Sofía López
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2264260155