Modulation of circadian rhythms through estrogen receptor signaling

Abstract Circadian rhythms are physiological and behavioral processes that exhibit a 24‐hr cycle. These daily rhythms are essential for living organisms to align their behavior and physiology with the environment to increase the likelihood of survival. In mammals, circadian rhythms synchronize with the environment primarily by the suprachiasmatic nucleus, a hypothalamic brain region that integrates exogenous and endogenous timing cues. Sex steroid hormones, including estrogens, are thought to modulate sexually dimorphic behaviors through developmental programming of the brain (i.e., organization), as well as acute receptor signaling during adulthood (i.e., activation). Importantly, there are known sex differences in the expression of circadian locomotor activity and molecular organization of the suprachiasmatic nucleus, likely due, in part, to the actions of circulating estrogens. Circadian locomotor rhythms, which are coordinated by the suprachiasmatic nucleus, have been shown to be regulated by developmental and adult levels of circulating estrogens. Further, increasing evidence suggests that estrogens can modulate expression of circadian clock genes that are essential for orchestration of circadian rhythms by the suprachiasmatic nucleus. In this review, we will discuss the organizational and activational modulation of the circadian timekeeping system by estrogens through estrogen receptor signaling.