The median preoptic nucleus is a key site for estradiol regulation of sleep-wake behaviors in females rats.

STUDY

OBJECTIVES

Women experience more sleep disruptions than men, particularly during hormonal transitions such as puberty, pregnancy, and menopause. This study investigated the role of estradiol (E2) in regulating sleep-wake behavior in female rats and identified the brain regions involved.

METHODS

Using an exogenous E2 replacement model in ovariectomized rats, we assessed changes in sleep-wake patterns via electroencephalographic/electromyogram telemetry. The effects of E2 and progesterone, selective estrogen receptor agonists, and direct brain infusions of E2 and receptor antagonists were evaluated.

RESULTS

E2 administration increased wakefulness, reduced non-rapid eye movement (NREM) and rapid eye movement sleep, and decreased NREM slow-wave activity (SWA), predominantly during the dark phase. These effects required both estrogen receptor alpha and beta activation and were mediated by estrogen receptor signaling within the median preoptic nucleus (MnPO). Direct infusion of E2 into the MnPO was sufficient to replicate systemic effects, while local infusion of the pure estrogen receptor antagonist ICI 182,780 (Fulvestrant) attenuated them. Progesterone did not augment E2's actions, and males showed no sleep-wake changes in response to E2, highlighting sex-specific mechanisms.

CONCLUSIONS

The MnPO is a critical site where E2 regulates sleep-wake behavior. These findings provide a neurobiological framework for understanding how ovarian hormones contribute to sleep disruptions in women, offering potential therapeutic targets for sleep disorders related to hormonal changes.