The transcription factor HHEX and the Androgen receptor (AR) drive the mouse adrenal sexual dimorphism

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 lipophagy induced by AR signaling and its absence results in glucocorticoid insufficiency in males. Overall design: CUT&Tag of the histone modification H3K27ac and AR in the male mouse adrenal gland. A total of 6 male mouse adrenals was dissociated and 280 000 nuclei were used per Cut&Tag reaction using the kit CUT&Tag-IT (Active motifi, #53170) and AMPure XP reagent (Beckman Coulter, A63880)