Faculty Collaboration Database

Sexual Differentiation of Circadian Clock Function in the Adrenal Gland. Endocrinology 2016 May;157(5):1895-904

Date

03/24/2016

Pubmed ID

27007073

DOI

10.1210/en.2015-1968

Scopus ID

2-s2.0-84969799416 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

Sex differences in glucocorticoid production are associated with increased responsiveness of the adrenal gland in females. However, the adrenal-intrinsic mechanisms that establish sexual dimorphic function remain ill defined. Glucocorticoid production is gated at the molecular level by the circadian clock, which may contribute to sexual dimorphic adrenal function. Here we examine sex differences in the adrenal gland using an optical reporter of circadian clock function. Adrenal glands were cultured from male and female Period2::Luciferase (PER2::LUC) mice to assess clock function in vitro in real time. We confirm that there is a pronounced sex difference in the intrinsic capacity to sustain PER2::LUC rhythms in vitro, with higher amplitude rhythms in adrenal glands collected from males than from females. Changes in adrenal PER2::LUC rhythms over the reproductive life span implicate T as an important factor in driving sex differences in adrenal clock function. By directly manipulating hormone levels in adult mice in vivo, we demonstrate that T increases the amplitude of PER2::LUC rhythms in adrenal glands of both male and female mice. In contrast, we find little evidence that ovarian hormones modify adrenal clock function. Lastly, we find that T in vitro can increase the amplitude of PER2::LUC rhythms in male adrenals but not female adrenals, which suggests the existence of sex differences in the mechanisms of T action in vivo. Collectively these results reveal that activational effects of T alter circadian timekeeping in the adrenal gland, which may have implications for sex differences in stress reactivity and stress-related disorders.

Author List

Kloehn I, Pillai SB, Officer L, Klement C, Gasser PJ, Evans JA

Authors

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

Adrenal Glands
Animals
Circadian Clocks
Circadian Rhythm
Estrous Cycle
Female
Male
Mice
Period Circadian Proteins
Sex Characteristics
Sex Differentiation
Testosterone