Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 338-357-Steroid Hormone Actions
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-354
Melanie E Peffer*, Yue Zhang, Marcia Lewis, Paula Monaghan-Nichols and Donald Benedict DeFranco
University of Pittsburgh School of Medicine, Pittsburgh, PA
While glucocorticoids (GCs) are clinically useful for a variety of conditions, their neonatal and prenatal use to aid lung maturation has been controversial due to adverse neurological and cognitive deficits that have been reported in humans and animals. Such alterations may reflect the impact of GCs on fetal neural progenitor/stem cell (NPSC) function. We have discovered that both genomic and non-genomic GC signaling in mouse NPSCs derived from E14.5 cerebral cortices contribute to the anti-proliferative effects of GCs. The rapid, non-genomic activation of mitogen activated protein kinase (MAPK) by glucocorticoid receptor (GR) leads to an inhibition of gap junction intercellular communication (GJIC) between coupled NPSCs and limits cell cycle progression. This pathway operates through plasma membrane GRs and requires the lipid raft associated protein, caveolin-1 (Cav-1). In embryonic NPSCs isolated from Cav-1 knockout mice, GC-induced MAPK activation, GJIC, and reduced proliferation are not observed. Furthermore, Cav-1 knockout impacts GC-dependent alterations in NPSC fate as monitored following in vitro differentiation. GC effects on NPSC fate require only a transient exposure to hormone and persist after multiple replicative divisions following hormone withdrawal. These findings suggest that a brief exposure to GCs during development can have a long lasting impact on brain development. Ongoing experiments will identify the GC dependent molecular and cellular processes that require Cav-1 in cerebral cortical NPSCs. To determine if Cav-1 dependent nongenomic activation of GR signaling impacts the genomic action of the receptor, a gene expression microarray analysis was performed using RNAs isolated from wild type or Cav-1 deficient NPSCs treated with GCs. Of the thousands of genes analyzed, approximately 100 genes were identified that are differentially regulated by GC treatment in wild type versus Cav-1 deficient NPSCs.  Preliminary data indicate that Cav-1 does not mediate these changes directly within the nucleus of NPSCs. Instead, Cav-1 ablation appears to impact basal and GC-regulated phosphorylation of the glucocorticoid receptor. Cav-1 is therefore a multi-functional regulator of GC action in NPSCs, both as a mediator of non-genomic signaling and by its novel role in altering genomic activity of the GR.

Nothing to Disclose: MEP, YZ, ML, PM, DBD

*Please take note of The Endocrine Society's News Embargo Policy at

Sources of Research Support: NIH grant T32-GM008424 awarded to MEP; NIH Grant RO1 DK078394 awarded to DBDG