Effect of Hhex and AR deletion on mouse adrenal gene expression

Glucocorticoids are cholesterol-derived steroid hormones produced by the adrenal gland and widely known for maintaining glucose homeostasis, modulating the immune system, and orchestrating the circadian rhythm. In this study, we defined HHEX as a key regulator of adrenocortical cell function. By using multiple transgenic mouse models, we demonstrate that HHEX shapes AR-dependent sexual dimorphism in the zF following the onset of puberty. HHEX protects lipid droplets integrity from lipid catabolism induced by AR signaling and its absence results in glucocorticoid insufficiency in males. Additionally, in both sexes, HHEX supports the inner zF transcriptome, including the expression of Abcb1b, a critical regulator of steroids and xenobiotics cellular levels.