FIGURE 3.

Expression of HIV Tat protein in mice increases basal corticotropin releasing hormone (CRH) and corticosterone. Upon stress, male (but not female) mice demonstrate adrenal insufficiency. The effects of Tat to dysregulate cholesterol homeostasis and alter steroidogenesis may contribute to the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. In normative systems, neuroactive steroids such as allopregnanolone restore HPA axis homeostasis, downregulating CRH, adrenocorticotropic hormone (ACTH) and glucocorticoid production