Estradiol modulates recovery of REM sleep in a time-of-day-dependent manner

Abstract

Ovarian hormones are thought to modulate sleep and fluctuations in the hormonal milieu are coincident with sleep complaints in women. In female rats, estradiol increases waking and suppresses sleep. In this study, we asked whether this effect is mediated via circadian or homeostatic regulatory mechanisms. Ovariectomized female rats received daily injections of estradiol benzoate (EB) or sesame oil that mimicked the rapid increase and subsequent decline of circulating estradiol at proestrus. In one experiment, animals were sleep deprived for 6 h starting at lights-on, so that recovery began in the mid-light phase; in the second experiment, animals were sleep deprived starting in the mid-light phase, so that recovery began at lights-off. EB suppressed baseline rapid eye movement (REM) and non-REM (NREM) sleep and increased waking in the dark phase. In both experiments, EB enhanced REM recovery in the light phase while suppressing it in the dark compared with oil; this effect was most pronounced in the first 6 h of recovery. By contrast, NREM recovery was largely unaffected by EB. In summary, EB enhanced waking and suppressed sleep, particularly REM sleep, in the dark under baseline and recovery conditions. These strong temporally dependent effects suggest that EB consolidates circadian sleep-wake rhythms in female rats.

Sex differences in sleep: impact of biological sex and sex steroids

“…Following a 6-h bout of sleep deprivation (SD), oestradiol facilitated REM recovery sleep in the light phase allowing a return to baseline levels in the dark phase. In contrast, control SD females exhibited increased REM sleep throughout the dark phase [125]. Asterisks represent statistically significant differences between the treatment groups (significance level set at 0.05 [133].…”

Exploring Sex and Gender Differences in Sleep Health: A Society for Women's Health Research Report

“…50 Finally, new emerging evidence suggests that estradiol consolidates circadian sleepwake rhythms in female rats lending to its novel role in interacting with both sleep and circadian regulation. 51 Evidence for the role of sex chromosomes in sleep regulation comes from two observations in mice: (1) sex differences in sleep propensity are not entirely eliminated by gonadectomy 5 (e.g., dissipation of SWA during recovery occurs more quickly in gonadectomized males compared with gonadectomized female mice); and (2) dissipation of sleep pressure after sleep loss is partially dependent on sex chromosomes. 48 Eventually, sex hormones and genetic mechanisms in conjunction with cultural and societal demands are thought to drive the sex and gender differences in sleep and sleep pathologies in humans.…”

The Neurobiology of Sleep and Wakefulness

“…324, 326 Circulating ovarian steroids, particularly estradiol and progesterone, are important for maintaining many of these effects. 327, 330, 332-334 Studies exploiting genetic tools to dissociate genetic and gonadal sex, along with use of classical neuroendocrine paradigms, recently showed that sex differences in sleep appear to be developmentally determined by a combination of genetic sex and gonadal hormone exposure. 335, 336 Estradiol downregulates the synthetic enzyme for PGD 2 , 337 increases Hcrt and Hcrt receptor expression levels, 338, 339 and modulates Fos expression in the VLPO and TM.…”