Faculty Collaboration Database

Chronic stress alters adrenal clock function in a sexually dimorphic manner. J Mol Endocrinol 2018 Feb;60(2):55-69

Date

01/31/2018

Pubmed ID

29378866

DOI

10.1530/JME-17-0146

Scopus ID

2-s2.0-85043778360 (requires institutional sign-in at Scopus site)   10 Citations

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.

Author List

Stagl M, Bozsik M, Karow C, Wertz D, Kloehn I, Pillai S, Gasser PJ, Gilmartin MR, Evans JA

Authors

Mary Bozsik MD Assistant Professor in the Emergency Medicine department at Medical College of Wisconsin
Jennifer A. Evans PhD Assistant Professor in the Biomedical Sciences department at Marquette University
Paul Gasser BS,MS,PhD Assistant Professor in the Biomedical Sciences department at Marquette University

MESH terms used to index this publication - Major topics in bold

Acute Disease
Adrenal Glands
Adrenocorticotropic Hormone
Animals
Chronic Disease
Circadian Clocks
Circadian Rhythm
Disease Models, Animal
Female
Male
Mice, Inbred C57BL
Restraint, Physical
Sex Characteristics
Stress Disorders, Post-Traumatic
Stress, Psychological