Steroid profiling of glucocorticoids in microdissected mouse brain across development

Area of Science:

• Neuroendocrinology
• Developmental Neuroscience
• Steroid Biochemistry

Background:

• Corticosterone is a key glucocorticoid hormone produced by adrenal glands and locally in organs like the brain.
• Local corticosterone levels within specific brain regions during development remain largely uncharacterized.

Purpose of the Study:

• To investigate region-specific and age-dependent local corticosterone levels in the developing mouse brain.
• To correlate brain corticosterone levels with systemic levels and identify predictive steroid precursors.
• To examine the expression of key steroidogenic enzymes in brain regions during development.

Main Methods:

• Microdissection of mouse brain tissue (hippocampus, cerebral cortex, hypothalamus) at postnatal days 5, 21, and 90.
• Development and application of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for steroid quantification.
• Measurement of gene expression for steroidogenic enzymes (Cyp11b1, Hsd11b1, Hsd11b2) in brain regions.

Main Results:

• Distinct regional patterns of corticosterone levels were observed across development, with higher levels in the hippocampus and hypothalamus than blood at PND5.
• Systemic corticosterone levels exceeded brain levels at PND21 and PND90; brain and blood levels were not consistently correlated.
• Local 11-deoxycorticosterone (DOC) predicted brain corticosterone at PND5, while 11-dehydrocorticosterone (DHC) was predictive at later ages. Enzyme gene expression varied by region and age.

Conclusions:

• Developing brain regions exhibit independent regulation of local corticosterone levels.
• The relationship between systemic and local brain corticosterone changes throughout development.
• Inter-regional coordination of glucocorticoid levels in the brain increases with age.