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.

Juvenile hormone affects the development and strength of circadian rhythms in young bumble bee (Bombus terrestris) workers

“…A third hypothesis states that JH has activational effects regulating functions in the central circadian network or downstream output pathways controlling locomotion. This idea is consistent with studies with rodents showing that sex steroids affect various circadian parameters of locomotor activity, including the phase, FRP, amplitude (i.e., strength), and splitting of locomotor activity rhythms (Daan et al, 1975;Morin, 1980;Morin et al, 1977; reviewed in Hatcher et al, 2020). Many of these effects could be attained by acute pharmacological treatments acting on hormone receptors indicating that the hormonal influence is activational rather than developmental (e.g., Karatsoreos et al, 2011;Model et al, 2015).…”

“…In mammals, it is well-established that sex steroid hormones have various organizational effects regulating the development of the circadian neural network and the expression of estrogen and androgen receptors which underlie sexual dimorphism in circadian activity (Hagenauer et al, 2011a(Hagenauer et al, , 2011bHummer et al, 2012;Melo et al, 2010;Royston et al, 2016;Sellix et al, 2013; for a recent review see Hatcher et al, 2020). Our findings that a single acute manipulation of JH levels shortly after adult eclosion from the pupa, resulted in relatively long term effects on the power of circadian rhythms best fit with the forth hypothesis stating that the influence of JH on circadian rhythms is mostly organizational.…”

Circadian rhythmicity and the community of clockworkers

“…Relevant here is the fact that sex differences have been demonstrated in the circadian timing system. Thus, oestrogens (Hatcher, Royston, & Mahoney, ) and androgens (Karatsoreos, Butler, Lesauter, & Silver, ) can modulate the expression of clock genes in the SCN. Furthermore, these sex‐typical steroids also modulate the expression of circadian locomotor behaviour (Model, Butler, LeSauter, & Silver, ) and alter sensitivity to photic cues (Butler, Karatsoreos, LeSauter, & Silver, ).…”

<p>Sleep and Methylation of Estrogen Receptor Genes, <em>ESR1</em> and <em>GPER</em>, in Healthy Middle-Aged and Older Women: Findings from the Women 40+ Healthy Aging Study</p>

“…28 Several lines of evidence from animal studies indicate that decreased levels of the three ERs may contribute to increase sleep problems and VMS. [29][30][31] To the best of our knowledge, no study has yet investigated the associations between ER gene methylation and sleep problems in middle-aged and older women. DNA methylation levels of specific regions of ER genes may contribute to alter sleep quality among women as they reach midlife.…”