Dissociation of Molecular and Endocrine Circadian Rhythms in Male Mice Lacking Bmal1 in the Adrenal Cortex

Endocrinology. 2016 Nov;157(11):4222-4233. doi: 10.1210/en.2016-1330. Epub 2016 Oct 3.

Abstract

The circadian rhythm of glucocorticoids affects diverse physiological systems, including stress responses and the coordination of rhythmic functions in peripheral and central tissues. Circadian clocks are considered to be important coordinators of glucocorticoid release and loss of the core clock component Brain and muscle Arnt-like protein-1 leads to ablation of behavioral and physiological rhythms, hypocortisolism, impaired ACTH, and behavioral stress responses. Transplantation and conditional clock gene knock-down studies in mice suggest an important role of local adrenocortical clock function in this context. Here, we present a Cre-loxP-mediated conditional knockout of Bmal1 in the steroidogenic cells of the adrenal cortex in mice. Mutant animals show a loss of molecular clock gene activity rhythms in this tissue with subsequent disruption of rhythmic steroidogenic gene expression. However, despite this loss of normal clock rhythmicity in the adrenal cortex, behavioral and physiological rhythms and acute stress responses persist in mutant mice. These findings reveal a dissociation of transcriptional and endocrine rhythm regulation in the adrenal cortex, arguing for a less pivotal function of the local clock machinery in the regulation of circadian and acute glucocorticoid outputs.

MeSH terms

  • ARNTL Transcription Factors / deficiency*
  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism
  • Adrenal Cortex / metabolism*
  • Adrenal Cortex Hormones / metabolism
  • Animals
  • Cholesterol Side-Chain Cleavage Enzyme / genetics
  • Cholesterol Side-Chain Cleavage Enzyme / metabolism
  • Circadian Rhythm / physiology*
  • Corticosterone / metabolism
  • Genotype
  • Glucocorticoids / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Physical Conditioning, Animal

Substances

  • ARNTL Transcription Factors
  • Adrenal Cortex Hormones
  • Arntl protein, mouse
  • Glucocorticoids
  • Cholesterol Side-Chain Cleavage Enzyme
  • Corticosterone