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Corticosteroid receptors and the central nervous system
1Baker Medical Research Institute, Melbourne, Australia.
Summary
Mineralocorticoid and glucocorticoid receptors in the central nervous system (CNS) function differently than in epithelia. These differences suggest distinct steroid hormone actions and novel response elements in the CNS.
Area of Science:
- Neuroendocrinology
- Molecular Endocrinology
Background:
- Aldosterone (aldo) and cortisol (F)/corticosterone (B) are key mammalian steroid hormones.
- Mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) are present in both epithelia and the central nervous system (CNS).
- Epithelial cells protect MR from glucocorticoids using 11 beta hydroxysteroid dehydrogenase (11 beta OHSD), ensuring aldosterone specificity.
Framework:
- CNS MR differ from epithelial MR; many are unprotected and act as high-affinity GR.
- In the CNS, aldosterone antagonizes glucocorticoids at these 'MR', unlike in epithelia.
- Activated GR in the CNS do not mimic activated MR, indicating receptor specificity.
Implementation:
- The study investigates the distinct roles and mechanisms of MR and GR in the CNS.
- It examines how steroid hormone concentrations influence receptor activation and downstream effects.
- The research explores the molecular basis of steroid hormone action in the brain.
Implications:
- Glucocorticoids may have dual action domains in the CNS, mediated by 'MR' at low concentrations and GR at high concentrations.
- CNS steroid hormone action likely involves non-canonical response elements distinct from those in epithelia.
- Understanding these CNS-specific mechanisms is crucial for neuroendocrine research and therapeutic development.