FP03-5 Widespread compartmentalization of glucocorticoid physiology during mouse development

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP03-Glucocorticoids & Glucocorticoid Actions
Basic/Translational
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:20 AM
Room 130 (Moscone Center)

Poster Board SAT-3
Matthew D Taves*1, Adam W Plumb2, Chunqi Ma2, Benjamin A Sandkam3, David A Close1, Ninan Abraham2 and Kiran K Soma2
1University of British Columbia, Vancouver, BC, 2University of British Columbia, 3Simon Fraser University, Burnaby, BC
Glucocorticoids (GCs) are secreted by the adrenal glands and circulate through the blood to coordinate organismal physiology. GCs play a paradoxical role in development, as they are critical for maturation of organs such as the liver and heart but simultaneously impair growth and neural development. The stress hyporesponsive period (SHRP), when circulating GCs are minimal soon after birth, avoids the harmful effects of GCs but conversely deprives organs of GCs where they are needed. Thus, temporal changes in systemic GC levels cannot meet the conflicting GC requirements of different organs during development. Interestingly, while the adrenals are traditionally considered the sole source of GCs, other organs also express GC-synthetic enzymes, suggesting that developing organs can independently regulate their local GC levels to correspond with organ-specific requirements. We quantified GCs in developing and adult mice and found that during the SHRP, GC levels in multiple organs were higher than in whole blood, consistent with constitutive local GC synthesis. Cortisol and its precursor deoxycortisol, widely considered to be absent in mice, were elevated in primary lymphoid organs (thymus and bone marrow), with cortisol concentrations in marrow up to 1000-fold higher than in circulating blood. Corticosterone and its precursors were elevated in lymphoid organs and liver, while deoxycorticosterone (both a GC and mineralocorticoid) was elevated in brain and heart. In lymphoid organs and heart, local GC elevation was most dramatic in the embryo and neonate, then decreased with age, showing that GC levels in different organs can be regulated independently of GC levels in blood. Thus, especially during early development, quantification of circulating steroids can be very misleading with regard to steroid levels in specific organs or tissues. Within the developing organism, there is clearly a “mosaic” of different steroids and different steroid concentrations, to match organ-specific developmental requirements. GC effects in different tissues should therefore be re-evaluated in the context of local (not just systemic) GC patterns.

Nothing to Disclose: MDT, AWP, CM, BAS, DAC, NA, KKS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This work was supported by a NSERC Discovery Grant to KKS, a CIHR Operating Grant to NA, and a CIHR Doctoral Fellowship to MDT.