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Chronic stress alters adrenal clock function in a sexually dimorphic manner.
- Source :
-
Journal of molecular endocrinology [J Mol Endocrinol] 2018 Feb; Vol. 60 (2), pp. 55-69. - Publication Year :
- 2018
-
Abstract
- Glucocorticoid production is gated at the molecular level by the circadian clock in the adrenal gland. Stress influences daily rhythms in behavior and physiology, but it remains unclear how stress affects the function of the adrenal clock itself. Here, we examine the influence of stress on adrenal clock function by tracking PERIOD2::LUCIFERASE (PER2::LUC) rhythms in vitro Relative to non-stressed controls, adrenals from stressed mice displayed marked changes in PER2::LUC rhythms. Interestingly, the effect of stress on adrenal rhythms varied by sex and the type of stress experienced in vivo To investigate the basis of sex differences in the adrenal response to stress, we next stimulated male and female adrenals in vitro with adrenocorticotropic hormone (ACTH). ACTH shifted phase and increased amplitude of adrenal PER2::LUC rhythms. Both phase and amplitude responses were larger in female adrenals than in male adrenals, an observation consistent with previously described sex differences in the physiological response to stress. Lastly, we reversed the sex difference in adrenal clock function using stress and sex hormone manipulations to test its role in driving adrenal responses to ACTH. We find that adrenal responsiveness to ACTH is inversely proportional to the amplitude of adrenal PER2::LUC rhythms. This suggests that larger ACTH responses from female adrenals may be driven by their lower amplitude molecular rhythms. Collectively, these results indicate a reciprocal relationship between stress and the adrenal clock, with stress influencing adrenal clock function and the state of the adrenal clock gating the response to stress in a sexually dimorphic manner.<br /> (© 2018 Society for Endocrinology.)
- Subjects :
- Acute Disease
Adrenal Glands drug effects
Adrenocorticotropic Hormone pharmacology
Animals
Chronic Disease
Circadian Rhythm drug effects
Disease Models, Animal
Female
Male
Mice, Inbred C57BL
Restraint, Physical
Stress Disorders, Post-Traumatic physiopathology
Adrenal Glands physiopathology
Circadian Clocks drug effects
Sex Characteristics
Stress, Psychological physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1479-6813
- Volume :
- 60
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of molecular endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 29378866
- Full Text :
- https://doi.org/10.1530/JME-17-0146