Estradiol Action at the Median Preoptic Nucleus is Necessary and Sufficient for Sleep Suppression in Female Rats

To further our understanding of how gonadal steroids impact sleep biology, we sought to address the mechanism by which proestrus levels of cycling ovarian steroids, particularly estradiol (E2), suppress sleep in female rats. We showed that steroid replacement of proestrus levels of E2 to ovariectomized female rats, suppressed sleep to similar levels as those reported by endogenous ovarian hormones. We further showed that this suppression is due to the high levels of E2 alone, and that progesterone did not have a significant impact on sleep behavior. We found that E2 action within the Median Preoptic Nucleus (MnPO), which contains estrogen receptors (ERs), is necessary for this effect; antagonism of ERs in the MnPO attenuated the E2-mediated suppression of both non-Rapid Eye Movement (NREM) and Rapid Eye Movement (REM) sleep. Finally, we found E2 action at the MnPO is also sufficient for sleep suppression, as direct infusion of E2 into the MnPO suppressed sleep. Based on our findings, we predict proestrus levels of E2 alone, acting at the MnPO, mediate sex-hormone driven suppression of sleep in female rats. Competing Interest StatementMDS is now an employee of Jazz Pharmaceuticals; the views expressed in this manuscript are solely the authors and do not reflect the views, policies or procedures of Jazz Pharmaceuticals.