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Modulation of hypothalamic hypocretin/orexin mRNA expression by glucocorticoids
Alain Stricker-Krongrad1, Bernard Beck
1Metabolic Diseases Physiology and Pharmacology, Millennium Pharmaceuticals, 75 Sidney Street, MA 02139, Cambridge, USA.
Biochemical and Biophysical Research Communications
|July 31, 2002
Summary
Glucocorticoids regulate hypocretin (Hcrt)/orexin (OX) pathway gene expression in rats. This finding suggests Hcrt/OX peptides are key relays for stress and feeding behaviors.
Area of Science:
- Neuroscience
- Endocrinology
- Molecular Biology
Background:
- Orexins (hypocretins) are hypothalamic peptides involved in energy homeostasis, feeding, and sleep-wake cycles.
- Glucocorticoids are known to influence stress responses and body weight regulation.
Purpose of the Study:
- To investigate the role of glucocorticoids in modulating the hypocretin (Hcrt)/orexin (OX) pathway in Sprague-Dawley rats.
- To determine if glucocorticoid status affects prepro-Hcrt/OX mRNA expression in the hypothalamus.
Main Methods:
- In situ hybridization was used to confirm the localization of prepro-Hcrt/OX mRNA expression in rat hypothalamus.
- Adrenalectomy was performed to remove endogenous glucocorticoids, followed by peripheral dexamethasone treatment.
Main Results:
- Adrenalectomy significantly decreased lateral hypothalamic prepro-Hcrt/OX mRNA expression by 50%.
- Glucocorticoid treatment with dexamethasone restored prepro-Hcrt/OX mRNA expression to normal levels.
- Prepro-Hcrt/OX mRNA expression is confirmed to be localized to the lateral hypothalamus, perifornical nucleus, and posterior hypothalamus.
Conclusions:
- Glucocorticoid status directly modulates hypocretin/orexin expression in the lateral hypothalamus.
- The hypocretin/orexin system interacts with corticotropin-releasing hormone and neuropeptide Y systems.
- Hypocretin/orexin peptides are proposed as sensitive relays for mediating stress and feeding behaviors.