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Primary Culture of Rat Adrenocortical Cells and Assays of Steroidogenic Functions
Published on: March 12, 2019
Liver X receptors regulate adrenal steroidogenesis and hypothalamic-pituitary-adrenal feedback
Maria Nilsson1, Thomas M Stulnig, Chin-Yo Lin
1Department of Biosciences and Nutrition, Karolinska Institutet, S-14157 Huddinge, Sweden.
Abstract:
The nuclear hormone receptors liver X receptor alpha (LXRalpha) (NR1H3) and LXRbeta (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 11beta-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.
Insights
Liver X receptors (LXRs) regulate metabolism and influence the adrenal and pituitary glands. LXR activation impacts steroid hormone production and the hypothalamic-pituitary-adrenal axis.
Area of Science:
- Endocrinology
- Molecular Biology
- Metabolism
Background:
- Liver X receptors (LXRs) are key regulators of cholesterol, lipid, and glucose metabolism.
- LXRs are potential therapeutic targets for diabetes and cardiovascular disease.
- Adrenal steroid hormones affect glucose metabolism, insulin signaling, and blood pressure.
Purpose of the Study:
- To investigate the genome-wide expression profiles of LXR-responsive genes in the adrenal and pituitary glands.
- To elucidate the role of LXRs in regulating the hypothalamic-pituitary-adrenal (HPA) axis.
Main Methods:
- Genome-wide expression profiling of LXR-responsive genes.
- In vitro studies using cultured adrenal and pituitary cells.
- In vivo studies involving LXR agonist treatment.
Main Results:
- LXR activation inhibited steroidogenic gene expression and reduced adrenal steroid hormone production.
- LXR agonist treatment increased ACTH mRNA expression and secretion from pituitary cells.
- LXR activation reduced 11beta-hydroxysteroid dehydrogenase 1 expression in pituitary cells, suggesting blunted glucocorticoid feedback.
Conclusions:
- LXRs directly interfere with adrenal steroidogenesis.
- LXRs modulate pituitary ACTH production and secretion.
- LXRs independently impact HPA axis regulation at both pituitary and adrenal levels.
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