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

Abstract

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 (MnPN), which contains estrogen receptors (ERs), is necessary for this effect; antagonism of ERs in the MnPN 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 MnPN is also sufficient for sleep suppression, as direct infusion of E2 into the MnPN suppressed sleep. Based on our findings, we predict proestrus levels of E2 alone, acting at the MnPN, mediate sex-hormone driven suppression of sleep in female rats.

Estradiol Influences Adenosinergic Signaling and NREM Sleep Need in Adult Female Rats

“…Our previous findings suggest this change in sleep may be mediated through E2 actions in the preoptic area (POA) sleep switches that include the , ventrolateral preoptic area (VLPO) 43,44,40 and the median preoptic nucleus (MnPO). 45 Moreover, these POA sleep nuclei have been implicated in sensing homeostatic sleep need. [46][47][48][49] The sleep homeostat governs the amount of sleep needed after a given period of wake to maintain homeostasis.…”