Liver X Receptors Regulate Adrenal Steroidogenesis and Hypothalamic-Pituitary-Adrenal Feedback
| Autor: | Ai Li Yeo, Peter Nowotny, Maria Nilsson, Edison T. Liu, Thomas M. Stulnig, Chin-Yo Lin, Knut R. Steffensen |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Pituitary gland medicine.medical_treatment Hypothalamus Receptors Cytoplasmic and Nuclear Biology Models Biological Mice Endocrinology Internal medicine Adrenal Glands medicine Animals Humans Liver X receptor Glucocorticoids Molecular Biology Liver X Receptors Feedback Physiological Mice Knockout Adrenal gland Gene Expression Profiling General Medicine Orphan Nuclear Receptors DNA-Binding Proteins Mice Inbred C57BL Steroid hormone medicine.anatomical_structure Nuclear receptor Pituitary Gland Steroids Hypothalamic–pituitary–adrenal axis Hormone |
| Zdroj: | Molecular Endocrinology. 21:126-137 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | The nuclear hormone receptors liver X receptor α (LXRα) (NR1H3) and LXRβ (NR1H2) are established regulators of cholesterol, lipid, and glucose metabolism and are attractive drug targets for the treatment of diabetes and cardiovascular disease. Adrenal steroid hormones including glucocorticoids and mineralocorticoids are known to interfere with glucose metabolism, insulin signaling, and blood pressure regulation. Here we present genome-wide expression profiles of LXR-responsive genes in both the adrenal and the pituitary gland. LXR activation in cultured adrenal cells inhibited expression of multiple steroidogenic genes and consequently decreased adrenal steroid hormone production. In addition, LXR agonist treatment elevated ACTH mRNA expression and hormone secretion from pituitary cells both in vitro and in vivo. Reduced expression of the glucocortioid-activating enzyme 11β-hydroxysteroid dehydrogenase 1 in pituitary cells upon LXR activation suggests blunting of the negative feedback of glucocorticoids by LXRs. In conclusion, LXRs independently interfere with the hypothalamic-pituitary-adrenal axis regulation at the level of the pituitary and the adrenal gland. |
| Databáze: | OpenAIRE |
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