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Related Experiment Video

Updated: Dec 22, 2025

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
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Peripheral clock system circadian abnormalities in Cushing's disease.

Vinicius Reis Soares1, Clarissa Silva Martins1, Edson Zangiacomi Martinez2

  • 1Department of Internal Medicine; Ribeirao Preto Medical School, University of Sao Paulo , São Paulo, Brazil.

Chronobiology International
|May 2, 2020
PubMed
Summary

Cushing's disease disrupts cortisol rhythm and clock gene expression in leukocytes. In healthy individuals, clock genes show circadian variation, which is lost in patients, except for CRY2.

Keywords:
Cushing’s diseaseCushing’s syndromeadrenalcircadian rhythmclock genesclock systemglucocorticoid

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Area of Science:

  • Chronobiology
  • Endocrinology
  • Molecular Biology

Background:

  • Cushing's syndrome is characterized by cortisol rhythm impairment.
  • This disruption may be linked to altered rhythmic expression of core clock genes.

Purpose of the Study:

  • To evaluate the expression of key clock genes (CLOCK, BMAL1, CRY1, CRY2, PER1, PER2, PER3) in leukocytes.
  • To compare gene expression patterns between healthy individuals and Cushing's disease patients.
  • To investigate the association between clock gene expression and cortisol circadian rhythm.

Main Methods:

  • Quantitative PCR (qPCR) was used to measure clock gene expression in peripheral blood leukocytes.
  • Salivary cortisol levels were measured at 0900h and 2300h.
  • The Cosinor method was employed to analyze circadian variations in gene expression.

Main Results:

  • Healthy controls exhibited circadian variation in CLOCK, BMAL1, CRY1, PER2, and PER3 expression.
  • PER1 and CRY2 expression lacked a specific pattern in controls.
  • Cushing's disease patients lost circadian variation in most clock genes, mirroring the abolished cortisol rhythm, though CRY2 showed a dark-phase acrophase.

Conclusions:

  • Cushing's disease is associated with disrupted circadian patterns of clock gene expression.
  • The altered expression of clock genes, particularly CRY2, may contribute to the loss of cortisol circadian rhythm in hypercortisolism.