Liver X receptor opens a new gateway to StAR and to steroid hormones.

Liver X receptors (LXRs) broadly limit cholesterol accumulation by regulating expression of genes involved in cholesterol efflux and storage. In this issue of the JCI, Cummins et al. report that LXRalpha is involved in similar regulation in the adrenal cortex, but it also substantially modulates glucocorticoid synthesis (see the related article beginning on page 1902). LXRalpha deletion in mice increases the availability of adrenal cholesterol for steroid synthesis by decreasing the expression of cholesterol efflux transporters. Glucocorticoid synthesis requires intramitochondrial cholesterol transport mediated by the steroidogenic acute regulatory protein (StAR). Surprisingly, LXR deletion and stimulation by an agonist each increase glucocorticoid synthesis. This parallels increased expression of StAR and several other steroidogenic genes.