ESR1 and ESR2 Differentially Regulate Daily and Circadian Activity Rhythms in Female Mice

Estrogenic signaling shapes and modifies daily and circadian rhythms, the disruption of which has been implicated in psychiatric, neurologic, cardiovascular, and metabolic disease, among others. However, the activational mechanisms contributing to these effects remain poorly characterized. To determ...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2014-07, Vol.155 (7), p.2613-2623
Main Authors: Royston, S.E, Yasui, N, Kondilis, A.G, Lord, S.V, Katzenellenbogen, J.A, Mahoney, M.M
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Circadian Rhythm - physiology
Estradiol - pharmacology
Estrogen Receptor alpha - agonists
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - physiology
Estrogen Receptor beta - agonists
Estrogen Receptor beta - physiology
Estrogens - pharmacology
Female
Mice
Mice, Inbred C57BL
Mice, Knockout
Motor Activity - drug effects
Motor Activity - physiology
Neuroendocrinology
Nitriles - pharmacology
Ovariectomy
Phenols
Photoperiod
Propionates - pharmacology
Pyrazoles - pharmacology
Running - physiology
Time Factors
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Summary:Estrogenic signaling shapes and modifies daily and circadian rhythms, the disruption of which has been implicated in psychiatric, neurologic, cardiovascular, and metabolic disease, among others. However, the activational mechanisms contributing to these effects remain poorly characterized. To determine the activational impact of estrogen on daily behavior patterns and differentiate between the contributions of the estrogen receptors ESR1 and ESR2, ovariectomized adult female mice were administered estradiol, the ESR1 agonist propylpyrazole triol, the ESR2 agonist diarylpropionitrile, or cholesterol (control). Animals were singly housed with running wheels in a 12-hour light, 12-hour dark cycle or total darkness. Estradiol increased total activity and amplitude, consolidated activity to the dark phase, delayed the time of peak activity (acrophase of wheel running), advanced the time of activity onset, and shortened the free running period (τ), but did not alter the duration of activity (α). Importantly, activation of ESR1 or ESR2 differentially impacted daily and circadian rhythms. ESR1 stimulation increased total wheel running and amplitude and reduced the proportion of activity in the light vs the dark. Conversely, ESR2 activation modified the distribution of activity across the day, delayed acrophase of wheel running, and advanced the time of activity onset. Interestingly, τ was shortened by estradiol or either estrogen receptor agonist. Finally, estradiol-treated animals administered a light pulse in the early subjective night, but no other time, had an attenuated response compared with controls. This decreased phase response was mirrored by animals treated with diarylpropionitrile, but not propylpyrazole triol. To conclude, estradiol has strong activational effects on the temporal patterning and expression of daily and circadian behavior, and these effects are due to distinct mechanisms elicited by ESR1 and ESR2 activation.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2014-1101