Chronic stress alters adrenal clock function in a sexually dimorphic manner

Area of Science:

• Chronobiology
• Endocrinology
• Neuroscience

Background:

• Circadian clocks regulate daily glucocorticoid production in the adrenal gland.
• Stress profoundly affects daily physiological rhythms, but its impact on the adrenal clock remains poorly understood.
• Understanding the interplay between stress and the adrenal clock is crucial for deciphering physiological regulation.

Purpose of the Study:

• To investigate how stress influences the molecular clockwork within the adrenal gland.
• To explore sex-specific differences in the adrenal clock's response to stress.
• To determine the role of the adrenal clock in mediating responses to adrenocorticotropic hormone (ACTH).

Main Methods:

• Tracking PERIOD2::LUCIFERASE (PER2::LUC) rhythms in adrenal glands from mice exposed to varying stress conditions.
• In vitro stimulation of male and female adrenal glands with ACTH to assess clock responses.
• Manipulation of stress and sex hormones to investigate their influence on adrenal clock function and ACTH responsiveness.

Main Results:

• Adrenals from stressed mice exhibited altered PER2::LUC rhythms compared to controls.
• The effects of stress on adrenal rhythms were dependent on sex and stress type.
• Female adrenal glands showed larger phase and amplitude responses to ACTH compared to male adrenal glands.
• Adrenal responsiveness to ACTH was inversely related to the amplitude of molecular rhythms, suggesting a role for clock amplitude in sex differences.

Conclusions:

• Stress reciprocally interacts with the adrenal clock, modulating its function.
• The adrenal clock's response to stress is sexually dimorphic.
• The state of the adrenal clock gates the adrenal response to ACTH in a sex-dependent manner.