Liver X receptors (LXRalfa and LXRalfa) act on the cholesterol homeostasis in several tissues, including adrenals. In particular, LXRalfa regulates the expression of several genes involved in the cholesterol efflux and storage and modulates glucocorticoid synthesis in mice. The level of the expression of LXRs in the human adrenal adenomas is unknown. We evaluated LXRalfa and LXRbeta mRNA levels in cortisol-secreting adenomas (CSA) and in the surrounding normal tissue, obtained from patients with Cushing syndrome underwent unilateral adrenalectomy; moreover, we studied the effects of the LXR agonist T09 on LXRs expression level and on cortisol release in adrenal cell primary cultures derived from CSA.
Methods: Total RNAs was extracted from 10 CSA and from 6 surrounding adrenal tissues. Quantitative real-time PCR was used to measure LXRalfa and LXRbeta transcripts. Primary culture of adrenal cells were set up from 2 CSAs and treated with 1 μM T09 or solvent as control. Cultures were harvested after 6 h (for expression study), and after 2448 h (for cortisol measurement by ELISA assay).
Results: LXRalfa and LXRbeta transcripts were found in CSA and surrounding adrenal tissue samples, and in primary cultured cells. LXRalfa resulted less abundant than LXRbeta in all samples; moreover, LXRalfa mRNA levels were lower in CSA than in surrounding adrenal tissues. LXRalfa expression increased after T09 treatment (P<0.01) in cultured adrenal cells. T09 induced also a 35% decrease of cortisol level after 48 h.
Conclusion: We demonstrate that LXRs are expressed in CSAs, with a lesser evidence of LXRalfa. LXR agonist modulates positively LXRalfa level and negatively cortisol secretion in primary cultured adrenal cells derived from CSAs. These data suggest a role of LXR mediated pathway in the pathogenesis of CSAs, and a potential use of LXR ligands in the control of cortisol secretion.
30 Apr - 04 May 2011
European Society of Endocrinology