Role of the nuclear receptors for oxysterols LXRs in steroidogenic tissues: Beyond the “foie gras”, the steroids and sex?

Various physiological functions have been ascribed to the liver X receptors (LXRs). Recently, we have identified new functions of these nuclear receptors in steroidogenic tissues. In adrenal, LXRα prevents accumulation of free cholesterol in mouse by controlling expression of genes involved in all aspects of cholesterol utilization. Under chronic dietary stress, adrenals from LXR-deficient mice accumulate free cholesterol while wild-type animals maintain cholesterol homeostasis through basal regulation of cholesterol efflux and storage. Hence, LXRα provides a safety valve to limit free cholesterol levels as a basal protective mechanism in the adrenal. Beside, mice lacking LXRα show lower levels of testicular testosterone while wild-type mice treated with the specific LXR agonist present an increase of testosterone production. Altogether, these data identify new roles for LXRs, in the regulation of cholesterol homeostasis in steroidogenic tissues and hormone synthesis.